What is neuroscience?

Study of the nervous system

o brain
o spinal cord
o nerves

INTRODUCTION
Evolution of nervous system
Charles Darwin: theory of natural selection
o different species evolved from common ancestor
o behaviour is heritable trait that can evolve
mammals have same reaction when scared: big pupils
Infer that the nervous systems of different species evolved
from common ancestors and may have common mechanisms
o rationale for animal experiments

ORIGINS OF NEUROSCIENCE

Pre-historic ancestors knew brain was vital to life

Evidence of skull surgeries (trepanation)

Ancient Egyptians thought heart (not brain) was:

o seat of the soul
o repository of memories (discarded brain after death)
Views of the brain: Roman Empire

Galen was Greek physician to gladiators

He was aware of:

o cerebrum
o cerebellum
o ventricles

Views of the brain: Renaissance to 19th C

Renaissance: brain seen as machine

o Descartes: brain only controls beast-like behaviour
mind controls uniquely human behaviour

17th & 18th C: observed white and gray matter in brain

End of 18th C: observed bumps (gyri) and grooves (sulci &

fissures) on brain

The neuron: the basic functional unit of the brain

NEUROSCIENCE TODAY
Neuroscientists

Years of education and training required

Two types of research:

1) clinical:
conducted by physicians
neurologists
psychiatrists
neurosurgeons
neuropathologists
study effects of brain damage
study benefits/risks of treatments
2) experimental:
conducted by M.D.s or Ph.D.s
neuroscientists
neurobiologists
neuroanatomists
neurochemists
The cost of ignorance

Research is expensive

Cost of ignorance about brain is greater

Disorders that affect nervous system:

o Alzheimers: degenerative disease of brain
o cerebral palsy: motor disorder
o depression: mood disorder

VIEWS OF THE BRAIN: 19TH C

Nerves as wires

Found muscles twitched when nerves stimulated electrically

Nerves are wires - conduct electrical signals to/from brain

Bell & Magendie: spinal roots carry info in diff. directions

o ventral roots contain only motor fibres
o dorsal roots contain only sensory fibres
Localisation of specific functions to different parts of brain

Bell:
o cerebellum is origin of motor fibres
o cerebrum is origin of sensory fibres

Marie-Jean-Pierre Flourens:
o used experimental ablation method
parts of brain destroyed to determine function
o cerebellum plays role in coordination of movement

Franz Joseph Gall:

o correlated structure of head with personality traits
(phrenology)

Broca:
o had patient who couldnt speak
o found a lesion in left frontal lobe of brain
o concluded this region of cerebrum responsible for speech

Others:

occipital lobe required for vision

NEURONS AND GLIA

Mitochondria

Sausage-shaped structures
Neurons and glia

Site of cellular respiration

Types of cells in the nervous system:

When mitochondria inhale:

1) neurons
1) they pull inside pyruvic acid and O2 from cytosol
2) glia
2) pyruvic acid enters Krebs cycle

More glia than neurons in brain

3) products of Krebs cycle enter electron-transport chain
o BUT neurons more important for functions of brain
yields ATP

When mitochondria exhale - ATP released

Neurons
1) sense changes in environment
THE NEURONAL MEMBRANE
2) communicate changes to other neurons
Barrier to enclose cytoplasm in neuron
3) command bodys responses to sensations
5nm thick
Studded with proteins
Glia
Protein composition varies
1) insulate
o depends on whether it is in the soma, dendrites or axon
2) support - neurons
3) nourish
THE CYTOSKELETON
Internal scaffolding
Gives neuron its shape
THE PROTOTYPICAL NEURON

Parts of neuron:
Three bones:
1) soma
1) microtubules
2) dendrites
2) microfilaments
3) axon
3) neurofilaments

Inside of neuron separated from outside by neuronal

THE AXON
membrane

All axons have:

o circus tent draped on internal scaffolding
1) beginning: axon hillock
2) middle: axon proper
THE SOMA
3) end: axon terminal

Spherical central part of neuron

Within the soma are the organelles:

Axon differs from soma (structure and function)
1) nucleus

ER doesnt extend into axon

2) rough ER
o no protein synthesis
3) smooth ER

Different proteins in axon membrane

4) golgi apparatus
5) mitochondria
o enables it to serve as telegraph wire send info
INTRODUCTION

Nucleus

Contains chromosomes (DNA)

The following occur in the nucleus:

1) gene expression: reading of DNA
2) transcription: assembling piece of mRNA
mRNA carries instructions for protein assembly
from nucleus to cytoplasm

Rough ER

Stacks of membrane

Dotted with globular structures: ribosomes

Major site of protein synthesis in neuron

Smooth ER

Rough ER without ribosomes

Processes protein molecules

Regulates internal conc. of substances

o e.g. calcium in muscle
Golgi apparatus

Stack of membrane-enclosed disks

Farthest from nucleus

Sorts newly synthesised proteins for delivery

Axon terminal

Where axon comes in contact with other neurons

Point of contact called synapse

Cytoplasm of axon terminal differs from that of axon:

1) doesnt have microtubules
2) has synaptic vesicles
3) has abundance of proteins
4) has numerous mitochondria (needs energy)
The synapse

Has 2 membranes (indicates direction of info. flow):

1) presynaptic: axon terminal
2) postsynaptic: dendrite/soma of another neuron

Synaptic cleft: space between membranes

Synaptic transmission: transfer of info at synapse

o Signals: electricalchemicalelectrical
DENDRITES

Extend from the soma

Resemble tree branches

Covered with synapses function as antennae of neuron

Membrane has receptors for neurotransmitters

CLASSIFYING NEURONS
Based on number of neurites that extend from soma

Neurites: axons and dendrites

o
o
o
Based on dendrites

Classification often unique to parts of brain

o 2 classes in cerebral cortex:
1) stellate: star-shaped
2) pyramidal: pyramid-shaped

Some have spines, some dont

o Spiny: spines
o Aspinous: no spines
Based on connections

Primary sensory neurons: connect with sensory surfaces

Motor neurons: connect with muscles

Interneurons: connect with other neurons

Based on axon length

Golgi type 1: long axons

o extend from one part of the brain to the other

Golgi type 2: short axons

o do not extend beyond cell body

Unipolar: 1 neurite
Bipolar: 2 neurites
Multipolar: 3+ neurites

MENTAL RETARDATION AND DENDRITIC SPINES

Mental retardation:
o sub-average cognitive functioning
o IQ < 70 (mean is 100)
o 2-3% of humans
Causes:
1) genetics
e.g. Down syndrome (extra chromosome 21)
2) accidents during pregnancy and childbirth
3) poor nutrition during pregnancy
4) environmental impoverishment

Due to changes in dendritic structure

o Fewer dendritic spines
o Spines long and thin

Dendritic spines important target of synaptic input

Good news: deprivation-induced changes are reversible

Based on neurotransmitter

Cholinergic: release acetylcholine at synapse

GLIA
Astrocytes

Most numerous glia in brain

Influence whether neurites can grow/retract

Regulate chemical content of fluid around neurons

(extracellular space)
Myelinating glia

Oligodendroglial and Schwann cells

Provide myelin sheaths around axons in brain & spinal cord

Mylelin sheath interrupted at nodes of Ranvier

Other non-neuronal cells

Ependymal cells: line fluid-filled ventricles in brain

Microglia: phagocytes remove debris (dead neurons/glia)

Vasculature of brain: arteries, veins, capillaries

ALZHEIMERS
Loss of brain function
Due to disruption of neuron cytoskeletons in cerebral cortex
First described by Alzheimer (1907)
51 year old patient
First symptom: jealousy towards husband
Then had memory impairment, confusion etc.
After she died, Alzheimer examined her brain
Noted changes in neurofibrils
Neurofibrillary tangles

Major component of tangles: Tau protein

o usually forms bridge between microtubules in axons
o ensures they run straight and parallel

In Alzheimers, Tau detaches from microtubules and

accumulates in soma
o causes axons to wither
o impedes information flow in neurons
What causes neurofibrillary tangle formation?

Abnormal secretion of amyloid by neurons

Possible therapy: reducing amyloid in brain

THE ACTION POTENTIAL

THE NERVE IMPULSE
PHASES OF ACTION POTENTIAL
Electrical current that travels along neuron
Due to ions moving through voltage-gated channels in the
neurons plasma membrane
NEURON AT REST
Charge difference between inside and outside of cell
Maintained by active transport using Na+-K+ pumps
o Send Na+ out and bring K+ in
Other channels allow flow of K+ out of cell
o But Na+ cannot get back in to replace lost +ve charges
Overall result: inside of cell more -ve than outside
o Different in charge = resting membrane potential
o -65mV in neuron

PROPERTIES OF ACTION POTENTIALS

THE ACTION POTENTIAL

Depolarisation
1) stimulus disturbs plasma membrane on dendrite
2) voltage-gated Na+ channels open
3) Na+ flows into cell
o depolarises the membrane
o local region inside of cell more +ve than outside

All or none
If threshold potential reached AP is generated
If threshold potential reached no AP is generated
Absolute refractory period (1msec)

AP cannot be generated, regardless of stimulus intensity

Relative refractory period (several msecs)

AP can be generated, but only with high-intensity stimulus

CONDUCTANCE OF ACTION POTENTIALS

Movement of AP along neuron

Continuous conduction

Occurs along unmyelinated axons

AP moves in series of tiny steps

Movement of depolarisation
4) neighbouring voltage-gated Na+ channels open
5) depolarisation moves along membrane (AP)

Restoring resting membrane potential

6) changes occur behind the AP:
o voltage-gated Na+ channels close
o voltage-gated K+ channels open
7) K+ flows out of cell
o repolarises the membrane
o inside of cell more ve than outside
o hyperpolarises the membrane

Saltatory conduction (saltare = leaping)

Occurs along myelinated axons

Myelin blocks flow of ions across membrane

AP jumps from one Node of Ranvier to another

Much faster than continuous conduction

Rate of conduction determined by
1) Myelination
o Myelinated axons conduct APs more quickly
2) Axon diameter
o Large axons conduct APs more quickly
3) Temperature
o Warm axons conduct APs more quickly
STUDYING ION CHANNELS
Patch clamp electrophysiology

Measures current flowing through ion channel

8)

Na+/K+ pumps establish proper concentrations of Na+ & K+

inside and outside the cell
o restores resting membrane potential

SYNAPTIC TRANSMISSION
WHAT IS IT?
Neuromuscular junction

Transfer of information from one neuron to another

Chemical synapse between:

o information flows in one direction
o axons of motor neurons of spinal cord
o skeletal muscle

At synapse (named by Charles Sherrington 1897)

One of the largest synapses in the body

Debate: chemical or electrical synapses?

Presynaptic terminal has active zones

Chemical: Otto Loewi (1921)

Postsynaptic membrane (motor end plate) has folds

o neurotransmitters transfer info.

Active zones line up with folds

Electrical: Edwin Furshpan & David Potter (1959)

o neurotransmitter released onto receptors
o electrical current transfers info.
Note: NMJ more accessible researchers than CNS synapses
ELECTRICAL SYNAPSES

Occur at gap junctions

o gap is spanned by clusters of connexin proteins
o 6 connexins combine to form channel: connexon
o 2 connexons combine to form a gap junction channel
o Channel allows ions to pass between cells

Cells connected by gap junctions are electrically coupled

Transmission is fast

When neurons are electrically coupled:

o AP in one neuron causes current to flow into 2nd neuron
o causes postsynaptic potential (PSP) in 2nd neuron
o the PSP generated by single electrical synapse is small
not enough to trigger an AP in the 2nd neuron
o several PSPs occurring at same time can trigger an AP

PRINCIPLES OF CHEMICAL SYNAPTIC

TRANMISSION

CHEMICAL SYNAPSES

Most synapses are chemical

Different types, but have universal characteristics

Universal characteristics

Neurons at chemical synapse separated by synaptic cleft

Axon terminal of presynaptic neuron has synaptic vesicles

Synaptic vesicles store neurotransmitter

o used to communicate with postsynaptic neuron
CNS synapses

Classified based on what forms synapse:

1) Axodendritic: axon + dendrite
2) Axosomatic: axon + cell body
3) Axoaxonic: axon + axon
4) Dendrodendritic: dendrite + dendrite

Classified based on membrane differentiations:

1) Grays type 1: asymmetrical and excitatory
2) Grays type 2: symmetrical and inhibitory

Basic requirements of chemical synaptic transmission

1) neurotransmitter synthesised
2) neurotransmitter packed into synaptic vesicles
3) vesicles spill contents into synaptic cleft in response to AP
4) response to neurotransmitter in postsynaptic neuron
5) neurotransmitter removed from synaptic cleft
Neurotransmitters

>40 important neurotransmitters discovered

Categories:
1) amino acids & amines
small organic molecules
stored and released from synaptic vesicles
2) peptides (amino acid chains)
large molecules
stored and released from secretory granules
Amino acids
GABA
Glutamate
Glycine

Amines
ACh*
Dopamine (DA)
Serotonin (5-HT)

Peptides
Dynorphin
Enkephalins (Enk)
Cholecystokinin (CCK)

* ACh was first neurotransmitter to be identified

NEUROTRANSMITTER SYNTHESIS AND STORAGE
Amino acids and amines

Enzymes convert precursors into neurotransmitter in cytosol

Neurotransmitter transported to synaptic vesicles in terminal

Peptides
Precursor peptide synthesised in rough ER
Precursor is split in Golgi apparatus
yields active neurotransmitter
Secretory granules containing peptide transported to
terminal

NEUROTRANSMITTER RECOVERY & DEGRADATION

Ways neurotransmitters are cleared:
1) diffusion away from synaptic cleft
2) diffusion and reuptake into presynaptic axon terminal
most amino acid and amine neurotransmitters cleared
this way
3) enzymatic destruction in synaptic cleft
ACh destroyed by AChE at NMJ
Important that neurotransmitter is cleared
o can cause desensitisation
o e.g. despite presence of ACh, ACh-gated channels close
- neuromuscular transmission fails
NEUROPHARMACOLOGY

Study of effects of drugs on nervous system tissue

NEUROTRANSMITTER RELEASE
1) AP arrives at axon terminal
2) Influx of Ca2+ through voltage-gated Ca2+ channels
3) Synaptic vesicles release contents into synaptic cleft by
exocytosis (vesicle membrane & presynaptic membrane
fuse)
4) Synaptic vesicle recycled by endocytosis

Receptor antagonists

Bind to receptors and block action of neurotransmitter

e.g. Curare (arrow-tip poison used to paralyse)

o blocks action of ACh
Receptor agonists

Bind to receptors and mimic actions of neurotransmitter

e.g. Nicotine
o binds to and activates ACh receptors in skeletal muscles
Defective neurotransmission

Root cause of many neurological and psychiatric disorders

SYNAPTIC INTEGRATION

The output of a single neuron is not enough to cause a

postsynaptic neuron to fire or prevent it from firing

The postsynaptic neuron must combine potentials from

many neurons to fire

These potentials are combined at the axon hillock in 2 ways:

1) spatial summation
combines potentials occurring simultaneously at
different locations on the dendrites and cell body
2) temporal summation
combines potentials arriving a short time apart

NEUROTRANSMITTER RECEPTORS & EFFECTORS

>100 different neurotransmitter receptors
Can be classified as:
1) transmitter-gated ion channels
2) G-protein coupled receptors

Summation of EPSPs and IPSPs

Summation combines EPSPs so AP more likely to occur

Summation combines IPSPs so AP less likely to occur

When both excitatory and inhibitory impulses arrive on a

neuron, they will also summate, but algebraically

Transmitter-gated ion channels

Membrane-spanning proteins

4/5 subunits come together to form pore

Less ion selectivity than voltage-gated channels

o ACh-gated ion channel at NMJ permeable to Na+ & K+
If channel permeable to Na+ (ACh, glutamate-gated channels)

Na+ will depolarise postsynaptic membrane

Brings membrane potential towards AP threshold

Causes excitatory post synaptic potential (EPSP)

If channel permeable to Cl- (glycine, GABA-gated channels)

Cl= will hyperpolarise postsynaptic membrane

Brings membrane potential away from AP threshold

G-protein coupled receptors

Slower, longer-lasting, more diverse postsynaptic actions

3 steps:
1) neurotransmitter binds to receptor proteins in membrane
2) receptor proteins activate G-proteins in cell
3) activated G-proteins activate effector proteins

Effector proteins can be:

a) ion channels in membrane
b) enzymes that synthesise second messengers

NEUROTRANSMITTER PRINCIPLES

NEUROTRANSMITTERS
PHASES OF ACTION POTENTIAL

Dales principle

A neuron will store/release only 1 neurotransmitter

Exceptions: peptide-using neurons

o GABAergic neurons secrete glutamate & GABA
NB: ergic = use

1 NT may be ligand for no. of different receptors

BUT no 2 NTs bind to same receptor

Co-transmitters

2+ NTs released from 1 nerve terminal

Divergence vs. convergence

Divergence:
o 1 NT
o Many effector systems

Convergence:
o Many NTs
o 1 effector system

NEUROTRANSMITTER RESEARCH
Immunocytochemistry

Localise specific molecules to particular cells

In situ hybridisation

Confirm that cells synthesises a particular protein

Needs autoradiography

Brain slices in vitro

Study release of chemicals when particular synapse
stimulated
Neuropharmacalogical analysis

Investigate receptors by studying action of drugs

RECEPTOR SYSTEMS
ACh (cholinergic) receptors

Nicotinic skeletal muscle

Muscaranic heart
Glutamate receptors

AMPA

NMDA

Kainite
NE (adrenergic) receptors

NE smooth muscles (involuntary)

NE heart, lung, skeletal muscle (voluntary)

NEUROTRANMITTER CHEMISTRY
Cholinergic (ACh) neurons
Catecholaminergic neurons
Serotonergic neurons
Amino acidergic neurons
RECEPTOR TYPES
Ionotropic: ligand gated channels

Nicotinic ACh

GABAA receptors

Glutamate receptors
How it works

Ligand binding opens channel

Metabotropic: G-protein coupled receptors

Muscarinic ACh

Adrenoceptors
How it works

Ligand binds to receptor

Receptor linked to intracellular G-protein

o has 3 subunits: (binds GTP),

Binding of ligand activates G protein

o GTP replaces GDP on subunit

G-protein dissociates

2 subunits interact with effectors

o enzymes, proteins, ion channels

Effectors activate 2nd messengers

o cAMP, Ca2+, phosphoionsitides

SOMATIC SENSATION TOUCH

INTRODUCTION TO SOMATIC SENSATION
Dermatome
Responsible for touch and pain

The area of skin innervated by a single spinal segment

Enables body to feel, ache, chill
Shingles
Different from other systems:

Infection of nerves
o receptors widely distributed

Increases excitability of sensory neurons

o responds to many types of stimuli

Leads to low thresholds of firing

TOUCH

Pain: burning and stabbing

Skin

Types:
1) hairy
2) glabrous (hairless)

Layers:
1) outer: epidermis
2) inner: dermis

Functions:
o Protective
o Prevents evaporation of body fluids
o Provides direct contact with world

Sensory organisation of spinal cord

Spinal code composed of:

o inner core of gray matter
o thick covering of white matter

Each half of spinal gray matter divided into:

1) dorsal horn
2) intermediate zone
3) ventral horn

Myelinated A axons (touch) enter dorsal horn and branch:

1) synapses in deep part of dorsal horn
2) ascends to brain

MECHANORECEPTORS OF SKIN

Most somatosensory receptors are mechanoreceptors

Sensitive to physical distortion (e.g. bending, stretching)

Types of mechanoreceptors (named after histologists):

o Pacinian corpuscle
o Ruffinis endings
o Meissners corpuscles
o Merkels disks
o Krause end bulbs

Mechanoreceptors vary in:

o receptive field sizes
small: Meisseners (small = meezly)
large: Pacinian
(large = packet)
o adaptation rate
rapidly adapting: response to stimuli does not persist
(e.g. Meisseners & Pacinian)
slowly adapting: response to stimuli persists

SOMATOSENSORY PATHWAYS TO BRAIN

Different pathways for:
o touch
o pain and temperature

Two-point discrimination

Ability to discriminate features of stimulus varies across

body
o e.g. fingertip better able to discriminate than elbow

Depends on:
o density of mechanoreceptors
o size of receptive fields
o amount of brain tissue devoted to sensory info
o special neural mechanisms
PRIMARY AFFERENT AXONS

Enter spinal cord through dorsal roots

o cell bodies lie in dorsal root ganglia

Axons from skin sensory receptors (in size order):

o A
o A (mediates touch)
o A
o C (mediates pain and temperature)

DORSAL COLUMN-MEDIAL LEMNISCAL PATHWAY

Major route for touch
Steps:
1) Axon 1 enters dorsal column of spinal cord
2) Axon 2 ascends to dorsal column nuclei
o at junction of spinal cord and medulla
3) Axon 3 ascends to ventral posterior (VP) nucleus of
thalamus
o through medial lemniscus (white matter tract)
4) Axon 4 projects to primary somatosensory cortex (S1)
TRIGEMINAL TOUCH PATHWAY
Route for somatosensory information from face
Steps:
1) Axon 1 (of trigeminal nerve) ascends to trigeminal nucleus
2) Axon 2 ascends to VP nucleus of thalamus
3) Axon 3 projects to primary somatosensory cortex (S1)
SOMATOSENSORY CORTEX

Somatosensory processing occurs here

Most of somatosensory cortex is in parietal lobe

Brodmanns area (3b or S1): primary somatosensory cortex

o lies on post-central gyrus

Other areas that process somatic sensory info:

o 3a, 1 & 2 (post-central gyrus)
o 5 & 7 (posterior parietal cortex)

Brodmanns area (3b or S1)

Primary somatic sensory cortex because:

1) receives dense inputs from VP nucleus of thalamus
2) its neurons are very response to somatosensory stimuli
THE SPINAL CORD
3) lesions here impair somatic sensation
Most peripheral nerves communicate w/ CNS via spinal cord
4) electrical stimulation causes somatic experience
Spinal cord encased in bony vertebral column
Areas 1 & 2
Segmental organisation of spinal cord

Receive input from area 3b

30 spinal segments divided into 4 groups:

o 3b 1: info about texture
o cervical (C) 1-8
o 3b 2: info about size and shape
o thoracic (T) 1-12
o lumbar (L) 1-5

10

sacral (S) 1-5

cut the lamb shanks

Cortical somatotopy

Mapping of bodys surface sensations onto structure in brain

Uses electrical stimulation of S1

Somatotopic map called homunculus

o not continuous (hand separates face and head)
o not scaled to human body (looks like caricature)

Size of body part related to importance of sensory input

o hands big used to identify objects
o mouth big used for speech and taste

Importance of body part varies in species

o rodents: facial vibrissae (whiskers) take up a lot of S1
Cortical map plasticity

Changes in brain as a result of ones experiences

Example violinists:
o continually finger strings with left hand
o amount of cortex devoted to fingers of left hand enlarged

Owl monkey experiment:

o cut off monkeys finger
o cortex originally devoted to that finger responded to
stimulation of adjacent fingers
Posterior parietal cortex

Involved in:
1) somatic sensation
2) visual stimuli
3) movement planning

Damage to posterior parietal areas can cause:

o agnosia: inability to recognise objects, though simple
sensory skills seem normal
o astereognosia: inability to recognise common objects by
feeling them
o neglect syndrome: part of body/world is ignored

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SOMATIC SENSATION PAIN

NOCICEPTORS
ASCENDING PAIN PATHWAYS
Free, branching, unmyelinated nerve endings
Differences between touch and pain pathways
Activated by stimuli that could cause tissue damage:
1)
nerve endings in skin
o strong mechanical stimulation
o touch - specialised structures in skin
o temperature extremes
o pain - free nerve endings
o oxygen deprivation
2)
diameter of axons
o chemicals
o touch - fat A fibres
Stimuli causes ion channels on nociceptor membrane to open
o pain - thin A and C fibres
3)
connections in spinal cord
Example: stepping on thumbtack
o touch - ascends ipsilaterally (same side of body)

Ion channels open due to:

o pain - ascends contralaterally (opposite side of body)
o stretching/bending of nociceptor membrane
o release of substances by damaged cells at site of injury
Brown-Sequard syndrome
proteases (break down kininogen to bradykinin)

Sensory & motor signs following damage to 1 side of body

ATP
+

Damage to left side will cause:

K
o loss of touch in left side
o loss of pain in right side
TYPES OF NOCICEPTORS
Mechanical: respond to strong pressure
Trigeminal pain pathway
Thermal: respond to extreme heat/cold

Route for pain information from face and head

Chemical: respond to chemicals (e.g. histamine)
Polymoidal: respond to all of the above

ALTERED PAIN SENSITIVITY

Hyperalgesia: increased sensitivity to pain
Hypoalgesia: reduced sensitivity to pain
Analgesia: absence of pain
Hyperpathia: exaggerated pain
Paresthesia: unpleasant sensations (e.g. burning, prickling)
Dysesthesia: distortion of senses
Alloydnia: pain after non-noxious stimulis
NERVE FIBRES THAT CARRY PAIN IMPULSES
A fibres

Large, myelinated fibres

Impulses travel quickly (fast pain)

Release glutamate at synapse w/ spinal neuron

C fibres

Small, unmyelinated fibres

Impulses travel slowly (slow pain)

Release glutamate & substance P at synapse w/ spinal neuron

First and second pain

A & C fibres bring info to CNS at different rates

Activation of nociceptors produces 2 perceptions of pain:

1) fast, sharp first pain
(A)
2) dull, long-lasting second pain (C)

Steps
1) Axon 1 (of trigeminal nerve) ascends to trigeminal nucleus
2) Axon 2 ascends to trigeminal lemniscus of thalamus
3) Axon 3 projects to cerebral cortex
NEURAL PATHWAY FOR PAIN
First-order neuron:
In dorsal root ganglia
Transmits sensory info. to dorsal horn of spinal cord
Second-order neuron:
In dorsal horn of spinal cord
Axons cross-over and ascend
Spinothalamic pathway thalamus
(neospinothalamic)
o identify pain location, intensity etc.
Spinoreticular pathway reticular formation
(paleospinothalamic)
o arouse organism in response to pain
Third-order neuron: in thalamus of brain
Relay information from thalamus to cerebral cortex
THE REGULATION OF PAIN
Afferent regulation

Pain evoked by activity in nociceptors can be reduced by

simultaneous activity in mechanoreceptors (A fibres)

Why it feels good to rub skin around bruise

Gate theory of pain explains these phenomena

Descending regulation

Strong emotion, stress or determination can suppress pain

Several brain regions implicated in pain suppression

o Periaqueductal gray matter (PAG)
o Electrical stimulation of PAG induces analgesia
Endogenous opiates

Opioids produce analgesia

Brain makes morphine-like substances (endorphins)

DESCRIBING PAIN
By origin

Cutaneous: from stimulation of skin and superficial tissues

12

By qualities

Referred: pain perceived at wrong location

o signals from diff. areas of body ascend using same route
o signals get mixed
o visceral pain (from organs) often felt in skin
e.g. angina - get pain in chest and left arm

Deep somatic: from stimulation of ligaments and bones

Visceral: from stimulation of receptors in internal organs

NEUROPATHIC PAIN
Chronic pain caused by damage to nerves
Neuropathic syndromes

Trigeminal neuralgia
o shooting neck and facial pain
o treatment:
anti-convulsants (e.g. carbamazepine)

Post-herpetic neuralgia
o complication of shingles
o pain persists after condition cleared
o treatment:
topical anaesthetics (e.g. lidocaine)
tricyclic anti-depressants (e.g. amitriptyline)

Complex regional pain syndrome (CRPS)

o pain in limbs after injury or trauma
o treatment:
analgesics

Phantom limb pain

o pain in amputated limb
o incidence: 70% amputees
o treatment:
hypnosis

13

BRAIN RHYTHMS/EPILEPSY
ELECTROENCEPHALOGRAPHY (EEG)
Categorisation based on frequency
Measure of electrical activity of brain

Beta (13-24) awake, alert

Caton (1875) used EEG on animal brains

Alpha (8-12) awake, quiet, resting

Berger (1929) used EEG on human brains

Theta (4-7) light sleep, REM sleep

o Found waking and sleeping EEG different

Delta (<4) deep sleep

o Large amplitude
Uses

Study sleep patterns

Diagnose disease

Locate tumors

Study drug effects

Determine brain death

How it works
Non-invasive electrodes attached to scalp
o international 10-20 system of electrode placement
o can compare EEG activity from different subjects

Records voltage produced by currents given off by brain

pyramidal cells

Can look at different regions of brain

Normal EEG

Brain waves change with:

Sensory stimuli

Age

Brain disease

Chemical state
Generation of synchronous rhythms

Synchronous rhythms can be:

a) led by a pacemaker (thalamus)
thalamic neurons have voltage-gated ion channels
allow each cell to generate rhythmic AP discharges
coordinated rhythms passed to neurons in cortex
b) arise from the collective behaviour of neurons

BRAIN WAVES

Waves of electrical activity

EEG measures wave:

o amplitude (height)
o frequency (cycles/sec)
Amplitude related to synchronisation of neuron activity

Each neuron receives many synaptic inputs

If inputs fire irregularly:

o pyramidal cell responses not synchronised
o summed activity has small amplitude

If inputs fire regularly:

o pyramidal cell responses synchronised
o summed activity has large amplitude

SEIZURES
Extreme form of synchronous brain activity
Neurons in cortex fire with abnormal synchrony
o Seizures case large EEG patterns
Epilepsy

Repeated seizures
Generalised seizures: entire cerebral cortex (both hemispheres)

Tonic-clonic (grand mal): loss of consciousness + muscle

contraction
o Status epilepticus: recurrent episodes of tonic-clonic

Absence (petit mal): abrupt loss of consciousness

o fluttering eyelids
o twitching mouth

Myoclonic: muscle jerks

Atonic: loss of muscle tone

Partial seizures: small area of cortex (1 hemisphere)
Simple: no loss of consciousness
Complex: impairment of consciousness
Symptoms:
o Frontal lobe: behavioural disturbance
o Temporal lobe: abnormal olfactory/gustatory sensation
fear
dj vu
o Occipital lobe: flashing lights
Secondarily generalised: spreads from 1 hemisphere to other
Provoked vs. unprovoked seizures

Provoked: known cause

Unprovoked: unknown cause

14

Causes

Alterations in ion distribution across neuronal cell membrane

o e.g. due to mutation in genes for Na+ channel proteins

Decreased inhibition of cortical neural activity

Neurotransmitter imbalances
o ACh
o GABA
SLEEP AND EPILEPSY

10% of patients have only night-time seizures

Happens during slow-wave sleep

Does not happen during REM sleep (no synchronisation)

Types of nocturnal epilepsy

Autosomal dominant nocturnal frontal lobe epilepsy

o linked to chromosome 8

Juvenile mycolonic epilepsy

o seizures occur while falling asleep and waking up

Nocturnal paroxysmal dystonia (NPD)

o seizures occur during non-REM sleep
Treatment

Anticonvulsant drugs (benzos)

o enhance GABA-mediated inhibition

Surgery to remove parts of brain

Surgery to implant vagus nerve stimulator

15

THE CHEMICAL SENSES - TASTE

TASTE
Perception of taste
Humans have sensitive taste system

Foods are different combinations of the basic types

Distinguishes between food and toxins

Taste and smell sensation work together

o otherwise onion could be mistaken for apple
Inborn preference for sweetness
o satisfied by mothers milk
TASTE RECEPTORS
Bitter substances instinctively rejected
Chemically
sensitive part of receptor: apical end: membrane
o many poisons are bitter
Apical ends have thin extensions: microvilli
o tolerance can lead to enjoyment (e.g. coffee)
Microvilli project into taste pore (opening on tongue)
Sense of taste decreases with
Taste receptors form synapses with:

Age (but less affected than olfaction)

o gustatory afferent axons near bottom of taste bud
o basal cells

Drugs

Disease
Activation of taste receptors
1) Chemical stimuli causes membrane depolarisation
THE ORGANS OF TASTE
2) Voltage-gated Ca2+ channels open
We taste with tongue
3) Ca2+ enters cytoplasm
Other areas of mouth involved:
4) Transmitters released
o palate
o we dont know what transmitter is
o pharynx
o epiglottis
TASTE TRANSDUCTION

Odors from food pass via pharynx into nasal cavity

Transduction: process by which stimulus causes electrical

response in sensory receptor cell
Papillae

Taste transduction involves several processes

Small projections on surface of tongue

Taste stimuli may:

Shaped like:
1) directly pass through ion channels (salt, sour)
o ridges (foliate papillae)
2) bind to and block ion channels (sour)
o pimples (vallate papillae)
3) bind to G-protein-coupled receptors in membrane that
o mushrooms (fungiform papillae)
open ion channels (bitter, sweet, umani)

Each papilla has hundreds of tastebuds

Saltiness
Taste buds

Taste of salt is taste of Na+

Each taste bud has 50-150 taste receptor cells

Salt-sensitive taste cells have Na+-selective channel

Taste receptor cells only 1% of tongue epithelium

Transduction:

Person has 2000-5000 taste buds

1) eat chicken soup

Cells of taste bud constantly replaced

2) Na+ conc. rises outside cell
3) Na+ passes into cell through Na+ channel
o lifespan: 2 weeks
4) Membrane depolarises
Threshold concentration
Sourness

Conc. of taste stimuli that evokes perception of taste

Foods taste sour because of high acidity

At threshold, papillae sensitive to 1 basic taste

o
Protons cause acidity and sourness

Above threshold conc., papilla less selective

Transduction method 1 (Na+ channel):

1) eat warhead
GUSTATORY DISCRIMINATION
2) H+ conc. rises outside cell
3) H+ passes into cell through Na+ channel
Basic taste types
4) membrane depolarises
1) Sweet

Transduction method 2 (K+ channel):

2) Salty
1) eat warhead
3) Sour
2) H+ conc. rises outside cell
4) Bitter
3) H+ binds to and blocks K+ channels
5) Unami (delicious): detected by receptors for amino acids
4) membrane depolarises
Gustatory discrimination
Bitter, sweet & umami

Taste regions: parts of tongue more sensitive to taste type

Bitter: calcium, quinine & poisons

Centre of tongue insensitive to taste stimuli

Sweet: sugars (carbs)

Umami: amino acids - glutamate, aspartate (broths, cheese)

Receptors are G-protein-coupled receptors

Formed by proteins: T1R & T2R

o Bitter receptor
30 types
formed by T2R
o Sweet receptor: TIR2 & TIR3
1 type
formed by T1R2 & T1R3 bound together
o Umami receptor:

16

1 type
formed by T1R1 & T1R3 bound together

Transduction:
1) eat bitter/sweet/umami food
2) taste stimuli binds to G-protein-coupled-receptor
3) activates phospholipase C
4) increases synthesis of IP3
5) IP3:
opens taste cell ion channel Na+ enters cell
opens voltage-gated Ca2+ channel Ca2+ enters cell
6) membrane depolarises

CENTRAL TASTE PATHWAYS

Flow of taste information is from:

1) taste buds
2) gustatory axons of cranial nerves
VII (facial): innervates anterior 2/3 of tongue
IX (glossopharyngeal): innervates posterior 1/3 of
tongue
X (vagus): innervates throat
3) medulla
gustatory nucleus
4) thalamus
ventral posterior medial (VPM) nucleus
5) cerebral cortex
primary gustatory cortex
in Brodmanns area 36

Lesions on VPM nucleus or primary gustatory cortex cause

ageusia (loss of taste perception)
NEURAL CODING OF TASTE
Population coding
Large number of broadly-tuned taste cells used to distinguish
between tastes

17

THE CHEMICAL SENSES - SMELL

SMELL
Axon
Combines with taste to help identify foods

Have thin, unmyelinated axon

Can warn of harmful substances (e.g. spoiled meat)

All the olfactory axons constitute the olfactory nerve

(cranial nerve I)
Mode of communication
o the olfactory axons do not come together as nerve bundle
o e.g. pheromones released by body
o they penetrate thin sheet of bone: cribriform plate
important for reproductive behaviour
o then course into olfactory bulb
mark territory
identify individuals

Olfactory axons are fragile

o can be damaged by blow to head or the flu
Sense of smell decreases with age due to
o result: anosmia inability to smell

Atrophy (wasting) of olfactory bulb

Loss of olfactory neurons

OLFACTORY TRANSDUCTION

Transduction molecules located in cilia

ORGANS OF SMELL
We do not smell with our nose!
Transduction pathway
1) Odorants bind to receptor proteins
Smell with olfactory epithelium
2) G-protein stimulated
3) adenylyl cyclase activated
Cell types of olfactory epithelium
4) cAMP formed
1) Olfactory receptor cells: site of transduction
5) cAMP binds to specific cation channel
o one of few types of neurons that gets replaced
6) cation channels open influx of Na+ and Ca2+
2) Supporting cells: help produce mucus
7) Ca2+-activated Cl= channels open efflux of Cl3) Basal cells: source of new receptor cells
8) membrane depolarisation
Olfactory epithelium covered with mucus
Termination of olfactory response

Mucus replaced every 10 mins

Response may terminate for several reasons:

Odorants dissolve in mucus before reaching receptor cells

1) odorants diffuse away

Mucus contains antibodies and binding proteins

2) scavenger enzymes in mucus break odorants down
o prevent viruses and bacteria entering brain
3) cAMP ends transduction process

Even if odorant still there, strength of smell fades

OLFACTORY RECEPTOR NEURONS
o receptor cells adapts to odorant within 1 min
Dendrite
Have single, thin dendrite
Dendrite ends with knob at surface of epithelium
Waving from the knob (within mucus) are long, thin cilia
o Odorants dissolved in mucus bind to cilia
o Activates transduction process

CENTRAL OLFACTORY PATHWAYS

Axons of receptor cells:
1) penetrate cribriform plate
2) enter olfactory bulb
3) synapse on 2nd-order neurons in glomerulus
receptors expressing particular gene all send axons to
same glomeruli
Second-order neurons go through olfactory tract to brain
o olfactory cortex
o neighbouring structures in temporal lobes

Unique - all other sensory systems pass through thalamus

before projecting to cerebral cortex
SPATIAL AND TEMPORAL REPRESENTATIONS OF
OLFACTORY INFORMATION
Olfactory population cloning

Each odor represented by large population of neurons

Olfactory maps

The neurons responsive to particular odors may be organised

into spatial maps
Temporal coding in olfactory system
The timing of APs may be essential code for particular odors
THE VOMERONASAL ORGAN: PHEROMONES
Accessory olfactory system used to detect pheromones
o mediates variety of social behaviours
o mothering, mating, marking territory
Runs parallel to primary olfactory system
Consists of vomeronasal organ in nasal cavity
o projects to accessory olfactory bulb

18

provides input to hypothalamus

19

CHEMICAL CONTROL OF BRAIN AND BEHAVIOUR

PATTERNS OF COMMUNICATION IN NERVOUS
Hypothalamus is part of limbic system
SYSTEM

Involved in processing emotions

Most systems we look at are point-to-point require:
o synaptic activation of target cells
Functional zones of hypothalamus
1) lateral
o signals of brief duration
These act over great distances for long periods of time time: 2) medial
3) periventricular
1) Neurons of secretory hypothalamus
affect many targets by releasing hormones into blood
Periventricular zone
2) Neurons of ANS

Receives inputs from:

work together to activate tissues all over body
o the other zones
3) Diffuse modulatory systems
o the brain stem
extend reach with divergent axonal projections
o the telencephalon
HYPOTHALAMUS

Has mix of neurons

o suprachiasmatic nucleus
Damage to..
synchronises circadian rhythms with light/dark

thalamus = discrete sensory/motor deficit

o neuroscecretory cells
o e.g. blind spot
secrete hormones into blood

hypothalamus = dramatic disruptions of body functions

o other cells that control ANS
Location of hypothalamus

Forms wall of third ventricle

Sits below thalamus

Connected to pituitary by stalk (infundibulum)

Functions of hypothalamus
1) homeostasis

Maintains bodys internal environment within narrow range

Regulates blood volume/pressure

1) drop in blood volume/pressure
2) kidney secretes renin into blood
3) renin promotes synthesis of angiotensin II
4) angiotensin II excites subfornical neurons
5) subfornical neurons stimulate hypothalamus
6) leads to increased ADH production & feeling of thirst
2) control pituitary

Pituitary dangles down below base of brain

Protected by bone

Mouthpiece from which hypothalamus speaks to body

2a) control posterior pituitary (part of brain)

Magnocellular neurosecretory cells extend down pituitary

These cells release 2 neurohormones:

o oxytocin causes uterus to contract, ejection of milk
o vasopression (ADH) regulates blood volume

2b) control anterior pituitary (gland)

Controlled by parvocellular neurosecretary cells

These cells secrete hypophysiotropic hormones into blood

of portal circulation
o travel to anterior pituitary
o bind to receptors on pituitary cells
o cause pituitary cells to secrete/stop secreting hormones

Regulates the stress response

o hypothalamus secretes CRH into portal circulation
o triggers release of ACTH into general circulation
o ACTH stimulates release of cortisol from adrenal gland
ANS
Periventricular zone of hypothalamus controls ANS
ANS is network of interconnected neurons
Somatic motor system + ANS = total neural output of CNS
o somatic motor system: commands skeletal muscle fibres
o ANS: commands every other tissue/organ
Sympathetic and parasympathetic divisions

Sympathetic division active during crisis

o increased HR & BP
o decreased digestion
o mobilised glucose reserves

Neurotransmitters

Preganglionic neurotransmitter: ACh

binds to nicotinic ACh receptors
evokes fast EPSP
usually triggers AP in postganglionic cell
o binds to muscarinic ACh receptors
evokes slow EPSP and IPSPs
Postganglionic neurotransmitter:
o sympathetic: norepinephrine (NE)
spreads far, even into blood
o parasympathetic: ACh
local effect on targets
o

Drugs that promote

NE are sympathomimetic
o effects mimic activation of SNS

muscarinic actions of ACh are parasympathomimetic

o effects mimic activation of PNS
DIFFUSE MODULATORY SYSTEMS

Neurons with widespread pattern of axons

Perform regulatory functions

Modulate numerous postsynaptic neurons

20

Parasympathetic division active at other times

o decreased HR & BP
o increased digestion
Act in parallel but use distinct pathways
o different structure
o different neurotransmitters

o make them more or less excitable

Essential for aspects of:
o motor control
o memory
o mood
o motivation

Common principles
1) core has small set of neurons
2) neurons arise from brain stem
3) each neuron can influence many others
4) synapses release neurotransmitters into extracellular fluid
o diffuse to many neurons (not just 1)

Enteric division

little brain

Neural system embedded in:

o oesophagus
o stomach
o intestines
o pancreas
o gallbladder

Consists of 2 networks:
1) myenteric (Auerbachs) plexus
2) submucus (Meissners) plexus

Controls transport and digestion of food

Receives input from of SNS and PNS

The four systems

1) noradrenergic locus coeruleus
2) serotonergic raphe nuclei
3) dopaminergic substantia nigra and ventral tegmental area
4) cholinergic basal forebrain and bran stem complexes

Neurotransmitters and the systems

Systems use NE, 5-HT, DA, ACh

These activate G-protein coupled receptors

Functions of systems depends on

How electrically active they are

How much neurotransmitter is available for release

Pontomesencephalotegmental complex
o ACh-utilising cells
o acts on dorsal thalamus
o regulates excitability of sensory relay nuclei

Drugs and the diffuse modulatory systems

Psychoactive drugs act on CNS by interfering with

chemical synaptic transmission
o Hallucinogens: LSD
o Stimulants: blocks reuptake of neurotransmitters
cocaine blocks DA reuptake
amphetamine blocks NE & DA reuptake

Noradrenergic locus coeruleus

Locus coeruleus is a tiny blue spot in the pons

We have 2 of them each has 12,000 neurons

Axons fan out to every part of brain innervate:

o spinal cord
o cerebellum
o thalamus
o cerebral cortex

Involved in regulation of:

o arousal
o sleep-wake cycles
o mood
Serotonergic raphe nuclei

Serotin-containing neurons clustered in raphe nuclei

Raphe = ridge
o raphe nuclei lie to either side of midline of brain stem

Each nucleus projects to different regions of brain

Innervate same areas & regulate same things as

noradrenergic system
Dopaminergic substantia nigra and ventral tegmental area

Substantia nigra and ventral tegmental area are in midbrain

Substantia nigra projects to stratium

o facilitates initiation of movement

Ventral tegmental area projects to limbic and frontal cortex

o involved in reward system
Cholinergic basal forebrain

Basal forebrain complex

o cholinergic neurons scattered among several related
nuclei at core of telencephalon
medial septal nuclei: innervate hippocampus
basal nucleus of Meynert: innervates neocortex
o function of cells unknown
death might cause Alzheimers?

MENTAL ILLNESS

21

INTRODUCTION
Neurology
Study of nervous system disorders

Neurological disorders help us understand normal brain

function
Psychiatry
Study of disorders that affect the mind e.g.
o anxiety disorders
o affective disorders
o schizophrenia
Mental illness
Disorder of through, mood or behaviour
Causes distress or impaired functioning
PSYCHOSOCIAL APPROACHES TO MENTAL ILLNESS
Freud
Mental illness results when unconscious and conscious
elements of psyche come into conflict
Skinner

Mental illness is learned maladaptive behaviour

BIOLOGICAL CAUSES OF MENTAL ILLNESS
Treponema pallidum infection

Causes general paresis of the insane (and syphilis)

Symptoms: mania, cognitive deterioration, paralysis

Treatments:
o Paul Ehrlich: arsphenamine
o Alexander Flemming: penicillin
Dietary deficiency in niacin (VitB)

Causes agitation, impaired reasoning & depression

ANXIETY DISORDERS
Fear

Adaptive response to threatening situations

Expressed by autonomic fight-or-flight response

Many fears are innate

o Mouse knows to fear cat

Fear also learned

o Horse learns to fear electric fence
Anxiety disorders

Inappropriate expression of fear

More common in women

Common anxiety disorders

Panic disorder (2% of pop.)

o frequent panic attacks

Agoraphobia (5% of pop.)

o anxiety about situations where escape is difficult
o e.g. in a crowd of people, on a bridge, in a lift

Obsessive-compulsive disorder (2% of pop.)

o obsessions cause anxiety
o compulsions neutralise anxiety
BIOLOGICAL BASES OF ANXIETY DISORDERS

Fear is evoked by threatening stimulus (stressor)

Stress response: reaction to stressor

In anxiety disorders, stress response occurs when:

o stressor not present
o stressor not threatening
Stress response

Characterised by:
1) avoidance behaviour
2) increased vigilance and arousal
3) activation of sympathetic division of ANS
4) release of cortisol from adrenal glands

HIV infection

Causes cognitive and behavioural impairments

Hypothalamic-pituitary-adrenal (HPA) axis

Secretion of cortisol from adrenal gland in response to stress

Steps:
1) CRH released from hypothalamus
corticotropin-releasing hormone
2) ACTH released from anterior pituitary
adrenocorticotropin hormone
3) Cortisol released from adrenal cortex
Regulation of HPA axis by amygdala and hippocampus

Amygdala activation stimulates HPA system (and stress)

Hippocampus activation suppresses HPA system

o has glucocorticoid receptors sensitive to cortisol
o important in feedback regulation of HPA axis
o prevents excessive cortisol release

Anxiolytic medications

Mediations that reduce anxiety

Alter chemical synaptic transmission in brain

Benzos: make GABAA receptors more responsive to GABA

o e.g. valium
SSRIs: prolong action of serotonin at receptors
o inhibit reuptake of serotonin
o e.g. fluoxetine
CRH receptor antagonists

AFFECTIVE (MOOD) DISORDERS (7% of pop.)

Characterised by disordered emotions

Major depression (5% of pop)

Most common mood disorder

Symptoms:
o lowered mood
o decreased interest/pleasure in activities
o loss of appetite
o insomnia
o fatigue
o feelings of worthlessness and guilt

22

diminished concentration

Dysthymia (2% of pop)

Mild form of depression

Continuous exposure to cortisol causes hippocampal damage

Continuous exposure to cortisol (during chronic stress)

causes hippocampal neurons to wither and die

Sets off vicious cycle:

1) stress response more pronounced
2) more cortisol released
3) more hippocampal damage
TREATMENTS FOR ANXIETY DISORDERS
Psychotherapy

Therapist increases exposure to anxiety-producing stimuli

Reinforces notion that stimuli are not dangerous

Cyclothymia

Cycles of hypomania and depression

BIOLOGICAL BASES OF AFFECTIVE DISORDERS
The monoamine hypothesis

Mood tied to levels of monoamine neurotransmitters

o NE and 5-HT

Depression due to deficit

Evidence:
o reserpine and MAO ( 5-HT) cause depression
o imipramine ( 5-HT) prevents depression

Bipolar disorder

Episodes of mania (elevated or irritable mood)

Symptoms:
o inflated self esteem
o decreased need for sleep
o increased talkativeness
o racing thoughts
o distractibility
o increased goal-directed activity

Type I (1% of pop): mania

Type II (0.6% of pop): hypomania

o mild form of mania
o can increase efficiency and creativity
o episodes of depression

2)

SSRIs: block reuptake of 5-HT

o e.g. fluoxetine
o increase neurogenesis (neuron synthesis) in hippocampus
3) NE-selective reuptake inhibitors: block reuptake of NE
o e.g. reboxetine
4) MAO inhibitors: reduce degradation of NE & 5-HT
o e.g. phenelzine
Lithium

Stabilizes mood of bipolar patients

Prevents mania and depression

The diathesis-stress hypothesis

Mood disorders caused by:

1) genetics
2) environmental factors

In depressed patients, HPA function is hyperactive

o due to decreased feedback inhibition
o due to diminished hippocampal response to cortisol
o due to deceased no. of glucocorticoid receptors
o due to abuse, neglect etc.
TREATMENTS FOR AFFECTIVE DISORDERS
Electroconvulsive therapy

Induces seizure activity in temporal lobes

o affects hippocampus regulates HPA axis

Anaesthetics & muscle relaxants prevent violent movements

Advantage: quick relief

Disadvantage: memory loss

Psychotherapy

Help depressed patients overcome negative views

Used to treat mild to moderate depression

Antidepressants (all increase NE & 5-HT)
1) tricyclic compounds: block reuptake of NE & 5-HT
o e.g. imipramine
o reduce HPA axis activity

23

increase no. of glucocorticoid receptors in hippocampus

24

AUDITORY SYSTEM: HEARING

THE NATURE OF SOUND
Eustachian tube

Sounds are audible variations in air pressure

Connects middle ear to nasal cavities
Important in pressure equalisation
Frequency

No. of compressed patches of air that pass by ears per second THE INNER EAR

Units: Hertz (Hz)

Consists of:
1) cochlea (auditory)

Range: 20 - 20,000 Hz
2) labrinyth (vestibular)

High frequency waves have high pitch

Intensity

High intensity waves are loud

STRUCTURE OF THE AUDITORY SYSTEM
Basic auditory pathway (TOOCS)
1) sound waves move tympanic membrane
2) moves ossicles
3) move membrane at oval window
4) moves fluid in cochlea
5) causes response in sensory neurons
THE MIDDLE EAR
Tympanic membrane
Ossicles

Types:
1) malleus
2) incus
3) stapes

Amplify sound
Muscles that attach to ossicles

Types:
1) tensor tympani
2) stapedius

Important in attenuation reflex

o loud sound causes muscles to contract
o ossicles become more rigid
o sound conduction to inner ear is diminished

PHYSIOLOGY OF COCHLEA
Organ of corti and associated structures

Auditory receptors (hair cells) located here

Each receptor has 100 hairy-looking sterocilia

Bending of cilia critical to transduction of sound

Transduction by hair cells
1) motion at stapes
2) basilar membrane moves upward
3) hair cell bends outward
4) mechanically-gated cation channels open
o TRPA1 (transient receptor potential) channels
5) K+ enters
6) depolarises hair cell
7) voltage-gated Ca2+ channels open
8) Ca2+ enters
9) neurotransmitter released onto spiral ganglion cells
o make up auditory nerve

ANATOMY OF COCHLEA
Cochlea

Spiral shape

Similar to drinking straw rapped 2.5x around pencil

Central pillar of cochlea (pencil): modiolus

At base of cochlea are 2 membrane-covered holes
1) oval window
2) round window
Tube divided into 3 fluid-filled chambers (scala = staircase)
1) scala vestibuli
o meets oval window
o fluid: perilymph
2) scala media
separated by basilar membrane
o fluid: endolymph
(basilar at BASE of cochlea)
3) scala tympani
o meets round window - organ of Corti is on membrane
(contains auditory receptors)
o fluid: perilymph
Perilymph vs endolymph

Perilymph: low K+ and high Na+

Endolymph: high K+ and low Na+

o similar to intracellular fluid

Endolymph has more +ve electrical potential

o called endocochlear potential
o enhances auditory transduction

CENTRAL AUDITORY PROCESSES

Signals travel from spiral ganglion to auditory cortex
Primary pathway (SVSIMA):
1) spiral ganglion
2) ventral cochlear nucleus
monoaural neurons: receive input from one ear
3) superior olive
binaural neurons: receive input from both ears
4) inferior colliculus
5) MGN
6) auditory cortex
SVSIMA: some very smart Indian maths academic

Innervation of hair cells

inner hair cells feeds 10 spiral ganglion cells

3 outer hair cells feed 1 spiral ganglion cell

Weird that:

25

o
o

more outer hair cells than inner hair cells

BUT 95% of cochlear output is from inner hair cells

Amplification by outer hair cells

Outer hair cells amplify sound

By increasing movement of basilar membrane

o Motor proteins (prestin) change length of outer hair cells
Stimulus frequency

Sources of information about sound frequency:

1) tonotopic maps
used for high and intermediate frequencies
2) timing of neural firing (phase locking)
used for low and intermediate freq.

Tonotopic maps on basilar membrane

o base of cochlear: membrane resonates w/ high freq.
o apex of cochlear: membrane resonates w/ low freq.
(think opposites!)

ENCODING SOUND INTENSITY & FREQUENCY

Stimulus intensity

Coded by:
1) firing rates of neurons
2) no. of active neurons
MECHANISMS OF SOUND LOCALISATION
Different techniques for locating sources in:
o horizontal plane (left-right)
o vertical plane (up-down)
Localisation of sound in horizontal plane

Sources of information about sound location:

1) interaural time delay
used for low freq. (20 2,000 Hz)
2) interaural intensity difference
used for high freq. (2,000 20,000 Hz)

Phase locking
o Cell fires at same phase of sound waves
frequency of sound same as frequency of APs
o Occurs with sound waves up to 4 kHz

Interaural time delay

o sound coming from right reaches right ear first

Interaural intensity difference

o sound comes from right left ear hears lower intensity
sound shadow on left
o sound comes straight on both ears hear same intensity
sound shadow behind head

Sensitivity of binaural neurons to sound location

Binaural neurons play role in sound localisation

First structure where present: superior olive

Localisation of sound in vertical plane
Based on reflections from the pinna

AUDITORY CORTEX
Primary auditory cortex (A1) on superior temporal lobe
Has tonotopic organisation
o strips of neurons for processing similar frequencies

26

Effects of lesions and ablation

Bilateral ablation: deafness

Unilateral lesion: normal auditory function

o different effect in visual cortex: blindness in 1 hemifield

27

VESTIBULAR SYSTEM: BALANCE

FUNCTIONS
THE SEMICIRCULAR CANALS
Functions:

Bulge along canal: ampulla

o monitors position and movement of head
o contains sheet of cells: crista
o gives sense of balance and equilibrium
contains hair cells

cilia project into gelatinous cupula

o coordinates movements of head and eyes
bathed in endolymph that fills canals
o adjusts body posture

When head rotates canal rotates

When function disrupted: motion sickness
o endolymh lags behind
VESTIBULAR LABYRINTH
o endolymph applies force to cupula

Interconnected chambers containing hair cells

o cilia bend
o excites/inhibits neurotransmitter release from hair cells

Made up of 2 structures:
1) otolith organs
Push-pull activation of semicircular canals
detect head tilt + acceleration
2) semicircular canals

3 semicircular canals
detect head rotation + acceleration

Each canal paired with another on opposite side of head

Transmit mechanical energy (head movement) to hair cells

Rotation:
o excites hair cells of one canal
THE OTOLITH ORGANS
o inhibits hair cells of partner canal

Pair of large chambers

1) saccule
CENTRAL VESTIBULAR PATHWAYS
2) utricle

Integrate info. about head/body movement

Each otolith has sensory epithelium: macula

Use it to control output of motor neurons

o contains hair cells

Pathway:
cilia project into gelatinous cap
1) Vestibular axons from cranial nerve VIII

When head straight macula is level

2) Vestibular nucleus
o cilia from hair cells straight
3) Ventral posterior (VP) nucleus of thalamus

When head tilted macula tilted

4) Neocortex
o gravity pulls the otoliths
o deform gelatinous cap
VESTIBULO-OCULAR REFLEX (VOR)
o cilia bend

Keep your eyes in particular direction when dancing

Works by sensing rotations of head

Transduction

Commands compensatory movement of eyes

Each hair cell has one tall cilia: kinocilium

Bending of hairs towards kinocilium results in depolarising

receptor potential

Transduction then same as auditory hair cells

28

MEMORY SYSTEMS & LEARNING 1

TYPES OF MEMORY
Transient global:
Learning: acquisition of new information
o retrograde amnesia for recent events
Memory: retention of learned information
o anterograde amnesia lasts minutes to days
o person appears disoriented, asks same questions
Declarative and non-declarative memory
o causes:

Declarative (explicit): for facts and events

cerebral ischemia (reduced blood flow to brain)
o results from conscious effort
concussion from trauma *rugby*
o can be accessed for conscious recollection
SEARCH FOR THE ENGRAM
o easy to form, easily forgotten
Engram: location of a memory

Non-declarative (implicit):
o Procedural: for skills, habits, behaviour
Lashleys studies of maze learning in rats
o results from direct experience

Studied effects of brain lesions on learning in rats

o cant be accessed for conscious recollection

Severity of learning deficits linked to size of lesions

o hard to form, hard to forget
o not location of lesions!
Long-term, short-term and working memory
Hebb and the cell assembly

Long-term: last days, months or years

How is external stimulus represented in brain activity?

Short-term: last seconds or hours

Theory:

Working:
1) external stimulus activates cortical cells (cell assembly)
o temporary form of information storage
cells are interconnected
o limited in capacity
2)
object
held in memory while activity in cell assembly
o requires rehearsal
3) if activation persists, consolidation occurs by growth
o studied by measuring persons digit span
process - makes connections more effective
(max no. of random numbers person can remember)
4) later: fraction of cells of assembly activated by stimulus
5) connections cause whole assembly to become activated
Memory consolidation

Suggested engram could:

1) Memories stored in short-term memory
o
be widely distributed among cell assembly connections
2) Memories selectively converted into permanent form
o
involve neurons involved in sensation/perception

BUT consolidation can occur without short-term memory

AMNESIA
Loss of memory and/or ability to learn
Causes:
o concussion
o chronic alcoholism
o encephalitis
o brain tumour
o stroke
Types of amnesia

Limited: most common after trauma

Dissociated amnesia: no other cognitive deficit

Retrograde: loss of old memories (discrete period)

Anterograde: inability to form new memories

Electrical stimulation of human temporal lobes
Causes flashbacks
Suggests temporal lobe important for learning & memory
THE TEMPORAL LOBES AND DECLARATIVE
MEMORY
Effects of temporal lobectomy

Expect it to have profound effect on learning & memory

Human study: H.M.

o medial temporal lobe removed to alleviate seizures
o no effect on perception, intelligence, personality
o BUT severe amnesia
partial retrograde amnesia - years before operation
extreme anterograde amnesia

cant form new declarative memories (facts)

Medial temporal lobes and memory processing
Important for declarative memory consolidation
Structures:
o hippocampus
o cortical areas ventral to (in front of) hippocampus

Localisation of declarative memories in neocortex

Hebb: if engram relies on visual info, will be in visual

cortex
o cortex processes sensory info and stores memories

Studies of visual discrimination consistent with this

Macaque monkeys: lesion study

Macaque monkeys trained to visually discriminate

After training, lesion made in visual cortex

Animal can no longer visually discriminate

Humans: fMRI study

Responses are specific to different objects

Visual cortex in bird experts more activated by bird images

Visual cortex in car experts more activated by car images

Medial temporal lobes and amnesia

Macaque monkey brain similar to human brain

Trained in delayed non-match to sample (DNMS) task

1) Monkey displaces sample object to get food
2) After delay 2 objects shown
3) Monkey displaces non-matching object to get food

Task requires recognition memory

Effect of bilateral medial temporal lesions on task:

o short delay: normal performance
o long delay: errors made (forgot sample object)

Conclusion lesions cause:

o anterograde amnesia
DIENCEPHALON AND MEMORY

Diencephalon is outside temporal lobe

It is associated w/ memory and amnesia

Regions of diencephalon involved in recognition memory
1) anterior thalamus
2) dorsomedial thalamus
3) mammillary bodies in hypothalamus

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entorhinal cortex rhinal cortex

perirhinal cortex
Damage to diencephalon and amnesia
parahippocampal cortex

Fencing foil went into N.A.s brain

o pathways that connect structures with other parts of brain
Lesion in left dorsomedial thalamus

Caused:
Information flow through medial temporal lobe
o retrograde amnesia 2 years
1) cortical association areas
o severe anterograde amnesia
2) parahippocampal and rhinal cortical areas
cant form new declarative memories
3) hippocampus

Very similar to what happened to H.M.

4) fornix

Medial temporal lobes and diencephalon both involved in

5) thalamus, hypothalamus
memory consolidation
Korsakoffs syndrome

Results from chronic alcoholism

Characterised by:
o confusion
o memory impairment
o apathy

Thiamin deficiency causes lesions to:

o dorsomedial thalamus
o mammillary bodies in hypothalamus
MEMORY FUNCTIONS OF HIPPOCAMPUS

Involved in diverse memory functions

o declarative memory
o recognition memory
o working memory
o relational memory (e.g. spatial relationships)
Effects of hippocampal lesions in rats: radial arm maze

Rat placed in 8 arm radial maze

If all arms contain food, rat goes down each arm once

If rat learns 4/8 arms never contain food, it will ignore these

Rat w/ hippocampal lesion:

o goes down same arms more than once
o leave arms containing food unexplored
lesion disrupts working memory

Effects of hippocampal lesions in rats: morris water maze

Rat placed in pool filled w/ water

Hidden platform below surface

Nave rat swims around until it bumps into platform

Normal rats learn the location of platform swim to it

Rat w/ hippocampal lesion:

o dont remember location of platform
lesion disrupts spatial memory

STRIATUM AND PROCEDURAL MEMORY

Basal ganglia control voluntary movements
Two elements:
1) caudate nucleus
striatum
2) putamen

Striatum:
o receives input from frontal & parietal cortexes
o sends output to
thalamus
cortical areas involved in movement
Lesion studies: light radial arm maze task

Small lights above arms containing food

Rat doesnt have to remember which arms it has explored

Has to form habit based on association between food & light

Lesion in striatum impaired performance in light maze

lesion disrupts procedural memory
Habit learning in humans and non-human primates

Parkinsons due to degeneration of inputs to striatum

Amnesia due to damage to temporal lobe

Memory task 1: cards (procedural memory)

o 4 cards presented in combinations
o icons indicate sun or rain
o patients had to learn to predict sun or rain
o amnesic patients improved
o Parkinsons patients didnt

Memory task 2: MCQ (declarative memory)

o series of MCQ asked
o Parkinsons patients were fine
o amnesia patients were impaired
THE NEOCORTEX AND WORKING MEMORY
Working memory: info held in mind for immediate need
o e.g. remembering phone number
o e.g. remembering arms of maze already explored
Hippocampus involved in working memory
BUT so is pre-frontal cortex

Pre-frontal cortex and working memory

Monkey: delayed-response task

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o monkey sees food placed in well below cover

o after delay, monkey chooses well
o gets reward if correct one
o lesion in pre-frontal cortex degrades performance
Human: Wisconsin card-sorting test
o person asked to sort deck of cards
o first by colour, then by shape
o lesion in pre-frontal cortex degrades performance
difficulty when sorting category changes
continue to sort according to old rule

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MEMORY SYSTEMS & LEARNING 2

INTRODUCTION
Non-associative learning in Aplysia
Hebb was right: memories can reside in synaptic alterations
Habituation of gill-withdrawal reflex

If water squirted onto Aplysia, the gill will retract

PROCEDURAL LEARNING
Amendable to investigation

Eventually, it habituates
Involves learning motor response in reaction to sensory input
Repeated stimulation of sensory nerve causes:
o reduced neurotransmitter release
Types:
o due to ineffective voltage-gated Ca2+ channels
1) non-associative learning
2) associative learning
o Ca2+ doesnt enter no AP
Non-associative learning
Sensitisation of gill-withdrawal reflex
Change in behavioural response to stimulus over time
Apply shock to head of Aplysia
Types:
Exaggerated gill withdrawal in response to siphon
1) habituation
stimulation
learn to ignore stimulus that lacks meaning

Strong stimulation of sensory nerve causes:

e.g. dog barking
o increased neurotransmitter release
2) sensitisation:
o due to closure of K+ channels
strong stimulus
o more Ca2+ enters during AP
learn to intensify response to all stimuli
e.g. in black out footsteps, headlights make you jump Associative learning in Aplysia
Associative learning
Form associations between events
Types:
1) classical conditioning
associate stimulus that evokes response (unconditional
stimulus) with second stimulus that doesnt evoke
response (conditional stimulus)
Pavlov: US = meat response = salivation CS = bell
2) instrumental conditioning
associate a response (motor act) w/ reward
e.g. rat pressing lever for food

Classical conditioning

US = strong shock to tail

Response = gill withdrawal

CS = stimulation of siphon

Pairing causes greater activation of adenylyl cyclase

o stimulates production of cAMP
o closes K+ channels
o increases neurotransmitter release
VERTEBRATE MODELS OF LEARNING

SIMPLE SYSTEMS: INVERTEBRAE MODELS OF

LEARNING
Invertebrate nervous systems have experimental advantages:
o small nervous system
o large neurons
o identifiable neurons
o identifiable circuits
o simple genetics

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ATTENTION
ATTENTION
Attention: selectively processing sources of info
Benefits performance of behavioural tasks
ADHD demonstrates how important attention is
What is happening in brain when paying attention?

Imaging studies show cortical activity is altered

BEHAVIOURAL CONSEQUENCES OF ATTENTION
Enhanced detection

Observer maintains steady fixation

Cue directs her to shift attention to one side of screen

Observer asked which side of screen circular target seen on

Detection more likely when cue on correct side (valid)

Faster reaction times

Reaction time faster when cue on correct side

Neglect syndrome as an attentional disorder

Person ignores objects and people to one side of gaze

o as if half of universe doesnt exist

Associated w/ damage to right cerebral cortex

o neglect objects to left side

Patients in denial
PHYSIOLOGICAL EFFECTS OF ATTENTION

Effects in numerous sensory areas from:

o area V1 in parietal lobe
o visual cortical areas in temporal lobes
fMRI imaging of attention to location (spotlight of attention)

Task:
o Subjects view stimulus
o Stimulus = line sectors radiating out from central point
o Orientation & colour of sectors changed ever 2 secs

Results:
o Enhanced activity in visual cortex
o Patch of enhanced activity associated w/ attended sector
PET imaging of attention to features

Task:
o Observer sees 2 frames
o Contain moving elements - change shape, colour, speed

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o Observer indicates whether stimuli are same or different

Results:
o Different areas of cortex active when different attributes
discriminated
colour & shape (blue & orange):

occipital lobe (V4 & IT)

temporal lobe
speed (green): MT middle temporal lobe

Enhanced neuronal responses in parietal cortex

Assumption: attention changes location before eyes move

Experiment by Wurtz, Goldberg, Robinson

Task:
o recordings made from parietal cortex of brain
area involved in directing eye movements
o monkey fixates on point on computer
o when target appears (in receptive field), animal makes
saccade to target

Results:
o parietal cortex had:
activity when target flashed in receptive field
enhanced activity when saccade to target occurred
o activity before saccade consequence of attention shift ?
Receptive field changes in area V4
HOW IS ATTENTION DIRECTED?
Pulvinar nucleus

In posterior thalamus

Role in guiding attention

Sends efferents to visual cortical areas of:

o occipital lobe
o parietal lobe
o temporal lobe
Attention and eye movements

Parts of brain that direct eyes play role in guiding attention

Frontal eye fields (FEF) cortical area

o FEF connected to areas influenced by attention in:
occipital lobe
parietal lobe
temporal lobe
o neurons in FEF have motor fields (areas in visual field)
o if current passed into FEF, eyes move to motor field of
stimulated neurons

Moores experiment
o current passed into FEF
o activity of neuron in V4 recorded
o stimulus presented FEF stimulation occurs after delay
o V4 response greater on trials with FEF stimulation
o Therefore FEF mimics effects of attention

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INTRODUCTION
Severe mental disorder
Major public health problem 1% of pop.

SCHIZOPHRENIA
Large changes in brain

Enlarged lateral ventricles

Indicates loss of brain tissue

Description of schizophrenia
Characterised by:
o loss of contact w/ reality
o disruption of thought, perception, mood, movement
Name means divided mind
o patients oscillate between normal and abnormal
Positive symptoms: abnormal thoughts/behaviours

Delusions

Hallucinations

Disorganised speech

Disorganised behaviour
Negative symptoms: absence of normal responses

Reduced emotion

Poverty of speech

Difficulty in initiating goal-directed behaviour

Memory impairment

Microscopic changes in brain

Defects in myelin sheaths around axons in cerebral cortex
Clusters of neurons in cortex
Changes in synapses and neurotransmitter systems
Dopamine hypothesis symptoms caused by:

Increased activation of DA receptors

o DA is inhibitory

Evidence:
o amphetamines cause dopamine release
o overdose leads to psychotic episodes
Glutamate hypothesis symptoms caused by:

Decreased activation of NMDA receptors (for glutamate)

o glutamate is excitatory

Evidence:
o phencyclidine (PCP) inhibits NMDA receptors
o causes positive and negative symptoms of schizophrenia

TREATMENTS FOR SCHIZOPHRENIA

Drug therapy
o conventional drugs (-azine, -idol)
act at D2 receptors
reduce +ve symptoms
o
atypical
drugs (-apine, -idone)
BIOLOGICAL BASES OF SCHIZOPHRENIA
dont act at DA receptors in striatum
reduce +ve and ve symptoms
Genes
Psychosocial
support

Schizophrenia runs in families

Chance declines as no. of genes you share w/ affected family Transcranial magnetic stimulation
o stimulation of frontal cortex reduces symptoms
member decreases
Types of schizophrenia

Paranoid: themed delusions

Disorganised: disorganised speech/behaviour

Catatonic: disruption of movement

Several genes found to increase susceptibility

o all have role in synaptic transmission/growth of synapses

Environment

If identical twin has it, 50% chance you will have it

Suggests genes make people vulnerable to enviro. factors:

o viral infections during development
o poor maternal nutrition
o stresses throughout life

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