108 • Physiology 3—Neurophysiology • 109

remain contracted for a period of time after the reflex learning. The cerebellum helps control the rate, range,
is activated. force, and direction of movements (collectively known Outer stellate cell
Parallel
as synergy). Damage to the cerebellum results in lack fibers
of coordination.
Control of Posture and Movement
The cerebellum is located in the posterior fossa just
by the Brain Stem
below the occipital lobe. It is connected to the brain
Descending motor pathways (i.e., those descending stem by three cerebellar peduncles, which contain both
from the cerebral cortex and brain stem) are divided afferent and efferent nerve fibers. Molecular layer
among the pyramidal tract and the extrapyramidal There are three main divisions of the cerebellum: the
Basket
tract. Pyramidal tracts are corticospinal and corti- vestibulocerebellum, the spinocerebellum, and the cell
cobulbar tracts that pass through the medullary pyra- pontocerebellum. The vestibulocerebellum is domi-
mids and descend directly onto lower motoneurons in nated by vestibular input and controls balance and eye Purkinje cell layer
Purkinje
the spinal cord. All others are extrapyramidal tracts. movements. The spinocerebellum is dominated by cell
The extrapyramidal tracts originate in the following spinal cord input and controls synergy of movement.
structures of the brain stem: The pontocerebellum is dominated by cerebral input,
via pontine nuclei, and controls the planning and initia-
♦ The rubrospinal tract originates in the red nucleus Climbing
tion of movements. fiber
and projects to motoneurons in the lateral spinal Golgi II
Granule
cord. Stimulation of the red nucleus produces activa- Layers of the Cerebellar Cortex cell
cells
tion of flexor muscles and inhibition of extensor
The cerebellar cortex has three layers, which are
muscles. Granular layer
described in relation to its output cells, the Purkinje
♦ The pontine reticulospinal tract originates in nuclei cells (Fig. 3.36). The layers of the cerebellar cortex are Glomerulus
of the pons and projects to the ventromedial spinal as follows:
cord. Stimulation has a generalized activating effect
♦ The granular layer is the innermost layer. It contains
on both flexor and extensor muscles, with its pre- Mossy fiber
granule cells, Golgi II cells, and glomeruli. In the
dominant effect on extensors.
glomeruli, axons of mossy fibers from the spinocer- Deep cerebellar nuclei
♦ The medullary reticulospinal tract originates in ebellar and pontocerebellar tracts synapse on den- Lateral vestibular nuclei
the medullary reticular formation and projects to drites of granule and Golgi type II cells.
motoneurons in the spinal cord. Stimulation has
♦ The Purkinje cell layer is the middle layer. It con- Fig. 3.36 Structures of the cerebellar cortex shown in cross-section.
a generalized inhibitory effect on both flexor and
tains Purkinje cells, and its output is always
extensor muscles, with the predominant effect on
inhibitory.
extensors.
♦ The molecular layer is the outermost layer. It con- fiber. These synaptic connections are powerful! A single action potentials called simple spikes. These
♦ The lateral vestibulospinal tract originates in the
tains outer stellate cells, basket cells, dendrites of single action potential from a climbing fiber can parallel fibers also synapse on cerebellar interneu-
lateral vestibular nucleus (Deiters nucleus) and
Purkinje and Golgi II cells, and axons of granule elicit multiple excitatory bursts, called complex rons (basket, stellate, and Golgi II).
projects to ipsilateral motoneurons in the spinal
cells. The axons of granule cells form parallel fibers, spikes, in the dendrites of the Purkinje cell. It is
cord. Stimulation produces activation of extensors
which synapse on the dendrites of Purkinje cells, believed that climbing fibers “condition” the Pur- Interneurons of the Cerebellum
and inhibition of flexors.
basket cells, outer stellate cells, and Golgi type II kinje cells and modulate their responses to mossy
The function of cerebellar interneurons is to modulate
♦ The tectospinal tract originates in the superior col- cells. fiber input. Climbing fibers also may play a role in
Purkinje cell output. With the exception of granule
liculus (tectum or “roof” of the brain stem) and cerebellar learning.
cells, all of the cerebellar interneurons are inhibitory.
projects to the cervical spinal cord. It is involved in Input to the Cerebellar Cortex ♦ Mossy fibers constitute the majority of the cerebel- Granule cells have excitatory input to basket cells, stel-
control of neck muscles.
Two systems provide excitatory input to the cerebellar lar input. These fibers include vestibulocerebellar, late cells, Golgi II cells, and Purkinje cells. Basket cells
Both the pontine reticular formation and the lateral cortex: the climbing fiber system and the mossy fiber spinocerebellar, and pontocerebellar afferents. Mossy and stellate cells inhibit Purkinje cells (via parallel
vestibular nucleus have powerful excitatory effects on system. Each system also sends collateral branches fibers project to granule cells, which are excitatory fibers). Golgi II cells inhibit granule cells, thereby
extensor muscles. Therefore lesions of the brain stem directly to deep cerebellar nuclei, in addition to their interneurons located in collections of synapses called reducing their excitatory effect on Purkinje cells.
above the pontine reticular formation and lateral ves- projections to the cerebellar cortex. Excitatory projec- glomeruli. Axons from these granule cells then
tibular nucleus, but below the midbrain, cause a dra- tions from the cerebellar cortex then activate secondary ascend to the molecular layer, where they bifurcate
matic increase in extensor tone, called decerebrate circuits, which modulate the output of the cerebellar and give rise to parallel fibers. Parallel fibers from Output of the Cerebellar Cortex
rigidity. Lesions above the midbrain do not cause nuclei via the Purkinje cells. the granule cells contact the dendrites of many The only output of the cerebellar cortex is via
decerebrate rigidity. Purkinje cells, producing a “beam” of excitation axons of Purkinje cells. The output of the Purkinje
♦ Climbing fibers originate in the inferior olive of the along the row of Purkinje cells. The dendritic tree of cells is always inhibitory because the neurotrans-
medulla and project directly onto Purkinje cells. each Purkinje cell may receive input from as many mitter released at these synapses is γ-aminobutyric
Cerebellum
These fibers make multiple synaptic connections as 250,000 parallel fibers! In contrast to the climbing acid (GABA) (see Chapter 1). Axons of Purkinje cells
The cerebellum, or “little brain,” regulates movement along the dendrites of Purkinje cells, although each fiber input to the Purkinje dendrites (which produce project topographically to deep cerebellar nuclei and to
and posture and plays a role in certain kinds of motor Purkinje cell receives input from only one climbing complex spikes), the mossy fiber input produces lateral vestibular nuclei. This inhibitory output of the
110 • Physiology 3—Neurophysiology • 111

cerebellar cortex regulates the rate, range, force, and neurotransmitter is glutamate. The overall output of
direction of movement (synergy). the indirect pathway is inhibitory, as illustrated in BASAL GANGLIA PATHWAYS
the summary diagram at the bottom of the figure.
Disorders of the Cerebellum +
♦ Direct pathway. In the direct pathway, the striatum Cortex
Cerebellar lesions result in an abnormality of move-
sends inhibitory input to the internal segment of the
ment called ataxia. Cerebellar ataxia is a lack of
globus pallidus and the pars reticulata of the sub-
coordination due to errors in rate, range, force, and +
stantia nigra, which send inhibitory input to the
direction of movement. Ataxia can be exhibited in one
thalamus. As in the indirect pathway, the thalamus
of several ways. There may be a delayed onset of Globus –
sends excitatory input back to the motor cortex.
movement or poor execution of the sequence of a pallidus Striatum
Again, the inhibitory neurotransmitter is GABA, and (external)
movement, causing the movement to appear uncoordi- + –
the excitatory neurotransmitter is glutamate. The
nated. A limb may overshoot its target or stop before
overall output of the direct pathway is excitatory,
reaching its target. Ataxia may be expressed as dysdi-
as shown in the summary diagram at the bottom of Substantia
adochokinesia, in which a person is unable to perform – nigra
the figure. – +
rapid, alternating movements. Intention tremors may (pars compacta)
occur perpendicular to the direction of a voluntary The outputs of the indirect and direct pathways from
movement, increasing near the end of the movement. the basal ganglia to the motor cortex are opposite and
(Intention tremors seen in cerebellar disease differ from carefully balanced: The indirect path is inhibitory, and + Globus Substantia
Subthalamic
pallidus nigra
the resting tremors seen in Parkinson disease.) The the direct path is excitatory. A disturbance in one of nuclei
(internal) (pars reticulata)
rebound phenomenon is the inability to stop a move- the pathways will upset this balance of motor control,
ment; for example, if a person with cerebellar disease with either an increase or a decrease in motor activity.
flexes his forearm against a resistance, he may be Such an imbalance is characteristic of diseases of the –
unable to stop the flexion when the resistance is basal ganglia.
removed. In addition to the basic circuitry of the indirect and
direct pathways, there is an additional connection, back Thalamus
and forth, between the striatum and the pars compacta
Basal Ganglia
of the substantia nigra. The neurotransmitter for the
The basal ganglia are the deep nuclei of the telencepha- connection back to the striatum is dopamine. This
lon: caudate nucleus, putamen, globus pallidus, and additional connection between the substantia nigra and Indirect pathway Direct pathway
amygdala. There also are associated nuclei including the striatum means that dopamine will be inhibitory
the ventral anterior and ventral lateral nuclei of the (via D2 receptors) in the indirect pathway and excitatory + +
thalamus, the subthalamic nucleus of the diencephalon, (via D1 receptors) in the direct pathway. –
and the substantia nigra of the midbrain. – –
The main function of the basal ganglia is to influence Diseases of the Basal Ganglia
the motor cortex via pathways through the thalamus. Diseases of the basal ganglia include Parkinson disease + – –
The role of the basal ganglia is to aid in planning and and Huntington disease. In Parkinson disease, cells of
execution of smooth movements. The basal ganglia the pars compacta of the substantia nigra degenerate, +, –, –, +, – = inhibitory +, –, – = excitatory
also contribute to affective and cognitive functions. reducing inhibition via the indirect pathway and reduc-
The pathways into and out of the basal ganglia ing excitation via the direct pathway. The characteristics Fig. 3.37 Pathways in the basal ganglia. The relationships between the cerebral cortex, the
are complex, as illustrated in Figure 3.37. Almost all of Parkinson disease are explainable by dysfunction of basal ganglia, and the thalamus are shown. Solid blue lines show excitatory pathways; dashed
areas of the cerebral cortex project topographically the basal ganglia: resting tremor, slowness and delay brown lines show inhibitory pathways. The overall output of the indirect pathway is inhibition, and
onto the striatum including a critical input from the of movement, and shuffling gait. Treatment of Parkin- the overall output of the direct pathway is excitation. (Modified from Kandel ER, Schwartz JH,
motor cortex. The striatum then communicates with son disease includes replacement of dopamine by Jessell TM: Principles of Neural Science, 4th ed. New York, McGraw-Hill, 2000.)
the thalamus and then back to the cortex via two treatment with L-dopa (the precursor to dopamine) or
different pathways. administration of dopamine agonists such as bromo- first organized in multiple associative areas of the The motor cortex consists of three areas: primary
criptine. Huntington disease is a hereditary disorder cerebral cortex and then transmitted to the supplemen- motor cortex, supplementary motor cortex, and premo-
♦ Indirect pathway. In the indirect pathway, the stria- caused by destruction of striatal and cortical cholinergic tary motor and premotor cortices for the development tor cortex.
tum has inhibitory input to the external segment of neurons and inhibitory GABAergic neurons. The neu- of a motor plan. The motor plan will identify the
the globus pallidus, which has inhibitory input to rologic symptoms of Huntington disease are choreic specific muscles that need to contract, how much they ♦ Premotor cortex and supplementary motor cortex
the subthalamic nuclei. The subthalamic nuclei (writhing) movements and dementia. There is no cure. need to contract, and in what sequence. The plan then (area 6) are the regions of the motor cortex respon-
project excitatory input to the internal segment of is transmitted to upper motoneurons in the primary sible for generating a plan of movement, which
the globus pallidus and the pars reticulata of the motor cortex, which send it through descending path- then is transferred to the primary motor cortex for
Motor Cortex
substantia nigra, which send inhibitory input to the ways to lower motoneurons in the spinal cord. The execution. The supplementary motor cortex pro-
thalamus. The thalamus then sends excitatory input Voluntary movements are directed by the motor planning and execution stages of the plan are also grams complex motor sequences and is active during
back to the motor cortex. In this pathway, the inhibi- cortex, via descending pathways. The motivation and influenced by motor control systems in the cerebellum “mental rehearsal” of a movement, even in the
tory neurotransmitter is GABA, and the excitatory ideas necessary to produce voluntary motor activity are and basal ganglia. absence of movement.
112 • Physiology

♦ Primary motor cortex (area 4) is the region of the desynchronized, with low-voltage, high-frequency
motor cortex responsible for execution of a move- waves that resemble those in an awake person. REM
ment. Programmed patterns of motoneurons are sleep is sometimes called paradoxical sleep: Even
activated from the primary motor cortex. As upper though the EEG is most similar to that of the awake
motoneurons in the motor cortex are excited, this state, the person is (paradoxically) most difficult to
activity is transmitted to the brain stem and spinal awaken. REM sleep is characterized by loss of muscle
cord, where lower motoneurons are activated and tone, notably in the eye muscles resulting in rapid eye
produce coordinated contraction of the appropriate movements, loss of temperature regulation, pupillary
muscles (i.e., the voluntary movement). The primary constriction, penile erection, and fluctuations in heart
motor cortex is topographically organized and is rate, blood pressure, and respiration. Most dreams
described as the motor homunculus. This topo- occur during REM sleep. The proportion of slow-wave
graphic organization is dramatically illustrated in sleep and REM sleep varies over the life span. New-
jacksonian seizures, which are epileptic events borns spend half of their sleep in REM sleep; young
originating in the primary motor cortex. The epileptic adults spend about 25% of sleep in REM sleep; and the
event usually begins in the fingers of one hand, elderly have little REM sleep.
progresses to the hand and arms, and eventually
spreads over the entire body (i.e., the “jacksonian
Learning and Memory
march”).
Learning and memory are higher-level functions of the
nervous system. Learning is the neural mechanism by
which a person changes his or her behavior as a result
HIGHER FUNCTIONS OF THE of experiences. Memory is the mechanism for storing
NERVOUS SYSTEM what is learned.
Learning is categorized as either nonassociative or
Electroencephalogram
associative. In nonassociative learning, exemplified by
The electroencephalogram (EEG) records electrical habituation, a repeated stimulus causes a response, but
activity of the cerebral cortex via electrodes placed on that response gradually diminishes as it is “learned”
the skull. The EEG waves originate from alternating that the stimulus is not important. For example, a
excitatory and inhibitory synaptic potentials that newcomer to New York City may be awakened at first
produce sufficient extracellular current flow across the by street noises, but eventually the noises will be
cortex to be detected by surface electrodes. (EEG waves ignored as it is learned they are not relevant. The
are not action potentials. Electrodes on the surface of opposite of habituation is sensitization, where a stimu-
the skull are not sufficiently sensitive to detect the lus results in a greater probability of a subsequent
small voltage changes of single action potentials.) response when it is learned that the stimulus is impor-
The normal EEG (Fig. 3.38) comprises waves with tant. In associative learning, there is a consistent
various amplitudes and frequencies. In a normal, relationship in the timing of stimuli. In classic condi-
awake adult with eyes open, the dominant frequency tioning, there is a temporal relationship between a
recorded over the parietal and occipital lobes is the beta conditioned stimulus and an unconditioned stimulus
rhythm (13–30 Hz), which consists of desynchronous that elicits an unlearned response. When the combina-
low-voltage, high-frequency waves. With eyes closed, tion is repeated, provided the temporal relationship is
the dominant frequency is the alpha rhythm (8–13 Hz), maintained, the association is learned; once learned
which has more synchronous waves of higher voltage (e.g., by Pavlov’s dog), the stimulus alone (e.g., the
and lower frequency. bell) elicits the unlearned response (e.g., salivation). In
As a person falls asleep, he or she passes through operant conditioning, the response to a stimulus is
four stages of slow-wave sleep. In Stage 1, the alpha reinforced, either positively or negatively, causing the
waves seen in an awake adult with eyes closed are probability of a response to change.
interspersed with lower-frequency theta waves. In Stage Synaptic plasticity is the fundamental mechanism
2, these low-frequency waves are interspersed with that underlies learning. That is, synaptic function and
high-frequency bursts called sleep spindles and large, effectiveness are variable and depend on the prior level
slow potentials called K complexes. In Stage 3 (not of activity or “traffic” through the synapse. The respon-
shown in the figure), there are very low-frequency delta siveness of postsynaptic neurons (called synaptic
waves and occasional sleep spindles. Stage 4 is charac- strength) is not fixed but rather depends on the previ-
terized by delta waves. Approximately every 90 minutes, ous level of synaptic traffic. For example, in the phe-
the slow-wave sleep pattern changes to rapid eye nomenon of potentiation, repeated activation of a
movement (REM) sleep, in which the EEG becomes neuronal pathway leads to increased responsiveness of