The Nervous System [Action Potential and Resting Potential]

(notes done by poopy, yooyi, soosy, and memo)

- All neurons which are considered the most excitable cells in the body can produce
electrical signals which is even called action potential by changing the permeability of
their cell membrane to certain ions.

- The cell membrane has a structure suitable to have a certain permeability to each
substance, especially ions, so then it is described as a selectively permeable membrane.
The cell membrane is made up of a phospholipid bilayer with many transport proteins
embedded in the structure.

- To understand how action potential travels, we need to understand the resting membrane
potential.

- Before the neuron is signaled and before it transmits action potential (excited), it should
be at rest, and after it is excited and signaled, it should restore its resting potential so it
can be triggered again.

- The resting membrane potential is the difference in the membrane voltage or electrical
potential between inside the cell and outside the cell at rest. This potential is a result of
the movement of ions through the cell membrane.
- If we connect the neuron’s cell membrane to a voltmeter at rest, the value of the resting
membrane potential measured will be approximately -70mv, and this value is for the
cytosol (inside the cell) relative to the reference (outside the cell), and the value is
negative which means that the negativity of the cytosol is more than the outside of the
cell at rest.

- The main ions which are found in different concentrations outside and inside of the cell
are Na+, Cl-, K+, and organic anions. At rest, the concentration of K+ is higher inside the
cell than outside, Na+ is more concentrated outside the cell than inside, Cl- is more
concentrated outside the cell than inside. Organic anions (which are negatively charged
organic molecules, mainly negatively charged proteins) are found inside the cell and not
found out of the cell because there are no transport proteins for them in the cell
membrane. These organic anions contribute significantly in the membrane potential.

- The ions mentioned above can move through the cell membrane by ion channels. There
are leak ion channels which are open all the time (without gates), and they cause the
movement of ions through the cell membrane. Because of that movement, we have a
resting membrane potential.

- What are the features or the causes that generate and establish the resting membrane
potential? We can list these factors as:

1) The concentration gradient for the ions (the chemical gradient):

→ The ions are distributed unevenly in the two areas of the cell membrane.
Because of this distribution, the ions move under that concentration (from a high
concentrated area to a low concentrated area which is called diffusion. It is a
 passive transport for these ions. This movement happens through leak ion
channels at rest).

2) Permeability:
→ The cell membrane does not have the same permeability for all substances and
all ions at the same level. This affects the resting potential directly (will be
mentioned in details)

3) Organic Anions:
→ The presence of organic anions in the cytosol which are stuck inside the cell
and increase the negativity.

4) The Na+/K+ ATPase pump:

→ It is very important in maintaining the resting potential and re-establishing it
after the action potential.

- To understand where the value of resting membrane potential comes from, imagine that
K+ is the only ion that crosses the cell membrane and there are only leak channels for K+
in that membrane.

- K+ is highly concentrated inside the cell than outside the cell at rest. So, it starts to
diffuse from inside to outside with concentration gradient force. It leaks and diffuses until
negativity increases more inside the cell. This creates an electrostatic force (electrical
gradient force) that attracts the K+ back toward the cell because of high negativity inside.
K+ keeps diffusing and is attracted back to the cell until it reaches the equilibrium (when
the net movement of K+ becomes zero, so for every K+ leaks out the cell, one K+ is
attracted in. The force that affects that movement is called electrochemical gradient. It
determines the direction of the movement. The membrane potential measured when K+ is
in equilibrium is called K+ equilibrium potential. In neurons, it is approximately -90mv.

- The question comes to our mind now, does the resting potential equal the k+ equilibrium
potential? The answer is close to it but not exactly equal to K+Ep (potassium equilibrium
potential).

WHY? The reason is K+ is not the only ion that leaks and moves through the cell
membrane. There is also Na+ which contributes as well.

- Now if Na+ is the only ion that moves through the cell membrane, Na+ should diffuse
inside to create enough electrical gradient (electrostatic force) that will attract Na+ out of
 the cell until it reaches equilibrium. Na+ equilibrium potential is approximately +60mv.
The resting potential is much closer to K+Ep than Na+Ep. So -70 is closer to -90 not +60.

WHY? Now, the second factor is the reason, the permeability of the cell membrane is
very high to K+ if you compare it with other ions. There are a lot of K+ leak channels.
90% of the total leak channels in the cell membrane is for K+. permeability means more
effect in the resting membrane potential.

- This is why K+ is the main contributor in the resting membrane potential.

Now, what about the Na+- K+ATpase pump? It is a transport protein that functions by
active transport. It pumps K+ and Na+ against their concentration. Which means Na+
will be pumped from inside to outside the cell and K+ from outside to inside the cell.
Active transport needs energy, ATP hydrolysis is the source of energy. This is why this
pump functions as an enzyme as well (ATpase).

- The main importance for this pump is to maintain the chemical gradient for both K+ and
Na+. Maintaining their chemical gradient causes their movement, so we have membrane
potential and action potential as well.

- After the action potential, we need to establish the resting potential, this pump helps
restore the chemical gradient for both Na+ and K+.

- More than 75% of the total energy generated by many cells is consumed for Na+/K+
pump. For example, in nephrons (a functional unit in the kidney), each cell has around 50
millions of the pump that maintains the Chemical gradient for Na+ and K+ that helps
these cells to remove toxins from the blood. in sperm cells, it helps sperm cells move and
penetrate the egg.

- How do Na+/K+ pump functions?

- The pump has two main configurations: one configuration opens it inward the cell, and
one configuration opens it outward the cell.

1. The pump is open inward toward the cytosol, it has a high affinity to Na. so 3 Na ions
bind to the pump and ATP molecules bind as well.
2. ATP hydrolysis (break into pi and ADP) : ADP is released to be recharged again into
ATP, Pi stays binded to the pump. Phosphorylation of the pump helps change its
configuration outward. Its affinity to Na decreases so Na leaves the pump and affinity to
K+ increases, so 2 K+ binds to their binding sites.

3. The pump will be dephosphorylated (Pi leaves the pump) so its configuration changes
again to inward. Once it opens inwards towards the cytosol, affinity to k+ will decrease.
So it is released and the affinity to Na+ will increase, so it binds and the cycle is repeated.
 - There is a common drug (medicine) called Digoxin that is prescribed to patients that have
some heart conditions like (heart failure or atrial fibrillation).

- The drug induces an increase in intracellular sodium by decreasing the functional

Na+,K+ pump into around 25%. It binds to the pump inhibits its dephosphorylation, so
Na+ can't bind to it and be pump out of the cell if Na+concentration increases inside the
cell this will induce Ca+2 influx of calcium and the release of Ca+2 from its storage,
increasing the contractility in cardiac muscle.
- (The drug reduces the activity of the Na+/K+ pump to 25%.
- This causes sodium to build up inside the cell.
- Higher sodium levels lead to an increase in calcium inside the cell.
- More calcium inside the cell makes the heart muscle contract more strongly.
- So, this drug indirectly increases the strength of heart muscle contractions by
manipulating sodium and calcium levels inside the cells.)

Action Potential

- Action potential is a rapid temporary shift in the membrane potential from negative into
positive by a rapid flow of cation (mostly Na+) from outside the cell into the inside of the
cell.

- The key behind having action potential is the chemical gradient (concentration gradient)
for the ions between inside and outside the cell.

- Action potential starts from axon Hillock in the neuron (The area or region of a neuron
where the axon extends out the cell body). It controls the initiation of the action potential
based on the inputs from other neurons or the environment which affects the dendrites
and the cell body.
- Action potential depends on or occurs mainly based on gated ion channels found in the
neuron cell membrane. It depends directly on voltage gated ion channels which are highly
concentrated in axon hillock and found also along the axon and axon terminal when
action potential should travel and reach.

- Gated ion channels are mainly ligand gated channels, mechanically gated channels and
voltage gated channels.

- Ligand gated ion channels open when a chemical binds to its receptor on that channel.
Neurotransmitter is the main chemical that causes these channels to open. Ligand gated
channels are found on dendrites and the cell body (The parts of the neuron could receive
the signal).

- Mechanically gated ion channels open when a mechanical energy is applied on these
channels like stretch, pressure or touch. This type of channels are mainly found on
sensory neurons.

- Voltage gated ion channels open when there is a change in the membrane potential.

- The main voltage gated ion channels involved in action potential are sodium voltage
gated ion channels and potassium voltage gated ion channels.

- Sodium voltage gated channels have 2 gates (activation gate and inactivation gate).

- This channel has 3 states: Closed (deactivated state), activated state and inactivated state.

- During a closed state, the activation gate is closed and the inactivation gate is open.
 → This state is during resting.

- During the inactivated state, the activation gate opens.

→ This state is during depolarization of action potential.

-During inactivated state → the activation gate is still open while the inactivation gate
shuts to prevent the flow in Na+ inside the cell.

→ this state occurs during repolarization of action potential.

- Potassium voltage gated channel has only one gate.

This gate is closed while This gate is open when the channel is active. K+
resting→ No flow out of K+ flows out (needed for repolarization of action potential).

Yasemin’s part
Action potential and graded potential

- The graph of action potential shows that it can’t occur if the membrane potential didn't
reach -55mv in axon Hillock.

- Threshold is the value of the membrane potential which if reached leads to action
potential so its determining the initiation of the action potential. Axon hillock is
considered as the trigger zone for action potential. If the change in membrane potential
moves from -70mv (resting potential) to -55mv (threshold) this change will be enough to
start all or don't start at all the action potential (if the neuron reaches the threshold in axon
hillocks the action potential will for sure travel along the axon and cause the release of
the neurotransmitters from axon terminal).

- What determines if the neuron will hit the threshold in axon hillock or not?
The answer is graded potential.

Graded potential:

- Graded potential is a localized change in membrane potential in a certain area in

dendrites or cell body. It's primarily generated by sensory input or a neurotransmitter.
Graded potential could be exciting or inhibiting. If it's exciting the stimulus will cause
flow in of positive charged ions (depolarization), (mainly Na+) in that area where the
neurotransmitter attaches like neurotransmitter binds to ligand gated channels. If the
graded potential is inhibiting, it causes flow in of negatively charged ions (maily Cl-)
toward the cell, or flow out of K+. In both cases the localized potential causes
hyperpolarization (increase in negativity).
 - Graded potential could have different sizes; large stimulus causes more change in
membrane potential or small stimulus could cause smaller change in membrane potential.

- The amount of neurotransmitter, the duration of its binding to the ligand gated channels
and the number of channels opened because of the neurotransmitter all can change the
size of graded potential. If the neuron was affected by multiple graded potential
(excitatory and inhibitory ) in synapses by different neurons all the graded potential will
be summed up in the axon hillock. Summation of the graded potential determines if the
membrane potential in the trigger zone will reach threshold or not.

- If the membrane potential reaches the threshold in axon hillock this is the initiation of the
action potential so it will travel for sure.

Action potential:

- The steps of action potential:

 1. Reach threshold in axon hillock which changes the membrane potential from
-70mv to -55mv.

2. Depolarization: threshold is considered as a stimulus for sodium gated channels to

open and move from closed state to activated state. Activation of sodium voltage
gated channels causes the rapid flow of Na+ to the cell changes the membrane
potential from -70mv to +40 mv or +35 mv which is the maximum of
depolarization.

3-Repolarization: when the membrane potential reaches +35mv (+40mv) this triggers Na+
voltage gated channels to do another transition in states from activated state to inactivated state
to stop Na+ flow in to the cell and activate K+ voltage gated channels to flow out K+ out of the
cell. Both of these changes change the membrane potential from +35mv toward -70mv (resting
potential) K+ leak channels can help in repolarization as well. once the membrane potential
reaches the resting potential after repolarization. Na+ voltage channels start to go back to a
resting state (closed state). It takes a little longer time for all Na+ channels to restore the closed
state.

4. Hyperpolarization.
→ Depolarization and repolarization take around 2ms together. It is supposed that the cell will
now restore the resting potential and can start a new action potential while the cell will have a
delay in returning to resting potential. The membrane potential will be more negative than -70
mV and may reach to -90 mV. This is hyperpolarization. It occurs because of the slow
inactivation of k+ voltage gated channels. They don’t close quickly, so more k+ leave the cell.
This delay is around 3.4 ms until all k+ channels become inactive and completely all Na+
voltage channels become closed. The Na+/k+ pump helps in reestablishing the resting potential
by restoring the chemical gradient for both Na+ and k+.

- Action potential is described as unidirectional potential. It goes in one direction from the
axon hillock to the axon terminal. Transition in states of Na+ voltage gated channels from
the activated state to the inactivated state to the resting closed state directly is the factor
that helps in having a unidirectional action potential. Action potential starts in the axon
hillock by having depolarization in this area which triggers more Na+ voltage gated
channels in the axon to open to have depolarization. While this area is depolarized, the
axon hillock will be in repolarization while the area next in the axon is still at rest.
Having repolarization because of inactivation of Na+ voltage channels is the reason why
action potential goes forward and doesn’t have backward movement. This sequence
continues until action potential reaches the axon terminal.
 - Action potential has one amplitude (one size) which doesn’t depend on the size of the
graded potential.

- Action potential may have different speeds based on many factors: the myelination of the
axon, the length of the axon, and the diameter of the axon. If the axon is myelinated, the
action potential will happen only in the nodes of ranvier (saltatory conduction) → faster
action potential. Shorter axon and more diameter will increase the speed of the action
potential.

The refractory period:

- It is a state of recovery that occurs after a neuron has fired an action potential. During this
period, another action potential can’t be easily produced. This helps a unidirectional
action potential and it regulates the frequency of action potential to limit the number of
action potentials that travel in a certain neuron during a certain duration of time. During
the refractory period, the neuron has resistance to start a new action potential. There are
two types of refractory periods:

1) The absolute refractory period:

→ During the absolute refractory period, the neuron absolutely cannot start a new
action potential no matter the strength of the stimulus. It happens during
depolarization and repolarization for around 2ms. → The reason for the 100%
resistance to start a new action potential is the Na+ voltage channels which are
activated or inactivated.

2) The relative refractory period:

 → During this period, the neuron can hardly start a new action potential if the
stimulus is much stronger than the previous stimulus to start a new action
potential during this refractory period. This period is during hyperpolarization of
the action potential (3.4ms). Action potential can start during hyperpolarization
because many Na+ voltage gated channels are closed so can be activated.
However, the membrane potential is more negative than the resting potential. So,
it is hard to shift that value around (-90 mV) to the threshold (-55mV).

Applications of the refractory period:

- The length of a refractory period can change if a certain chemical can affect the ion
channels.

1) Alcohol.
→ Drinking alcohol can increase the length of the refractory period by binding to Na+
voltage gated channels while they are inactivated. This causes the sodium channels to
take a longer time to restore the closed state. The person that drinks alcohol has slower
actions.

2) Lidocaine is a drug used as a local anesthetic during applying a procedure on a tooth or as

antiarrhythmic to regulate the electrical signals on the heart. Lidocaine binds to
inactivated Na+ voltage gated channels to block them in this state, increasing the length
of the refractory period as a local anesthetic. This causes numbness in this region of the
gum without having sensation temporarily.
 [Brain Structure and Function]

- The brain is a complex organ that controls all the functions in the body and controls
thought, memory, emotion, touch, motor skill, vision, breathing, temperature, hunger,
sleep and wake cycle and more.

- The brain is made up of around 60% fat. The remaining about 40% is water, protein,
carbohydrates, salt and ions. The brain is not a muscular tissue, but it contains blood
vessels and nerves, including neurons and glial cells.

- The brain is protected by the skull, specifically by the cranial bones of the skull. The
cranial bones are occipital bone, 2 temporal bones, 2 parietal bones, frontal bones,
ethmoid and sphenoid.

- The brain is covered by a sac called meninges. Meninges are three membrane layers that
protect the brain and the spinal cord. The three layers that make the meninges are: Dura
mater, Arachnoid mater and pia mater.

Generally, those layers:

- Provide a supportive framework for the brain.

- Act with the cerebrospinal fluid to protect the CNS
 - Supply the brain with blood by including branches of major arteries.

A) Dura Mater: It is the outermost layer of the meninges. It is composed of 2 layers. The
outer one is the periosteum and the inner which is the meningeal layer. The periosteum
consists of very dense fibrous connective tissue that contains cells like fibroblasts and
osteoblast with very dense and large quantities of collagen fibers. The meningeal layer is
less dense than the periosteum. Dura mater is rich with blood vessels. Within the 2 layers
of dura mater there are some spaces called venous sinuses or dural sinuses. These cavities
or sinuses include branches of major veins that drain and collect the deoxygenated blood
with many byproducts and CO2 toward the major vein called internal jugular vein that
carries this blood superior vena cava toward the right atrium of the heart.

B) Arachnoid Mater: It is the second layer of meninges it is between dura mater and pia
mater. It is avascular layer (doesn’t include any blood vessels). It is made up of loose
connective tissue (less fibers). Under the arachnoid mater there is a layer called
subarachnoid, it is between arachnoid and pia mater. Subarachnoid layer is the
cerebrospinal fluid-filled space. Within the lateral ventricles of the brain, the
cerebrospinal fluid is produced by a blood vessel rich tissue called choroid plexus and
secreted by ependymal cells. This fluid fills the lateral ventricles and passes into the
subarachnoid space. CSF (cerebrospinal fluid) functions to cushion the brain and the
spinal cord, supply them with nutrients and remove wastes. The wastes in CSF are
drained from subarachnoid space to dural sinuses for drainage out of the brain.
Subarachnoid space includes major branches of arteries.

C) Pia Mater: The deepest layer of the meninges. It hugs the brain directly. It contains
connective tissue of elastic fibers and collagen fibers. It includes blood vessels and a
layer of epithelial tissue.

Brain views and sections: We can study the brain structure from different views.

a) Superior view of the brain surface shows the top of the brain where the cerebral cortex
will be visible. Part of the frontal lobe, the parietal lobes, part of occipital lobes will be
visible as well. The longitudinal fissure is seen as well.
b) Inferior view of the bottom view of the brain. It is mainly an inferior view of the
cerebrum. All cerebrum lobes except the parietal lobe can be seen. The brainstem and
cerebellum. All cranial nerves are shown in the inferior view.

c) Anterior view of the brain is a front view showing mainly the frontal lobe.

d) Posterior view of the brain is the back view, it shows the occipital lobe and cerebellum.

e) Lateral view is a side view, you can see the temporal lobe, part of the occipital lobe,
spinal cord, part of the parietal lobe…

- To visualize the internal structure of the brain, there are three standard anatomical planes
that can be used to have three different section views. They help in diagnosis conditions
through imaging techniques like MRI. These planes are: the sagittal plane, the coronal
plane and horizontal or axial plane.

a) Sagittal plane is the vertical plane through the longitudinal fissure that splits the brain
into left and right hemispheres.

b) Coronal plane is a frontal plane that vertically splits the brain into the front and back
sections.

c) The horizontal plane splits the brain into upper and lower sections.

- Sagittal Section: Can visualize many structures in the brain. Corpus Callosum is visible.
It is an area of white matter that includes a lot of nerve fibers that connect the 2 brain
hemispheres together. The Sagittal view visualizes the three parts of the brain stem
(midbrain, pons and medulla oblongata). Half of the cerebellum is visible. Pituitary gland
 which comes exactly under the hypothalamus. The diencephalon area (thalamus,
hypothalamus and epithalamus). The third ventricle that encloses the diencephalon. In
addition, all cerebral lobes can be seen partially.

- The coronal view or section visualizes main structures. You can see the gray matter and
white matter. The corpus callosum, lateral ventricles also can be seen.

Gray Matter and White Matter

- The gray matter is the area of the cerebral cortex or the cerebellum as well which comes
in the cortex (outer surface part of these structures). It includes the dendrites, cell bodies
and synapses of neurons.

- The white matter is the center part of the cerebrum, cerebellum and brainstem. It is
composed of bundles of axons. Specifically myelinated axons. White matter conducts,
and sends nerve signals without the brain and spinal cord.
Sulci and Gyri:

- The surface of the brain, known as the cerebral cortex, is very uneven. It is characterized
by a pattern of folds and grooves. The folds are gyri (singular: gyrus), and the grooves are
the sulci (singular: sulcus).
- They form important landmarks that help separate the brain into functional centers.
- Having these gyri increases the surface area of the cortex, allowing for greater function
and communication. Together, gyri and sulci give the brain its wrinkled appearance.
- The human has the most complex gyri and sulci.
- The human female has more complex gyri and sulci than the human male since the male
has a larger brain.
- The gyri are found on the surface of the cerebral cortex and are made up of grey matter,
so it includes synapses of the cerebrum. This is why having larger gyri and more gyri
means having more cognition and abilities. The process of development of gyri
(gyrification) starts early in embryonic development (week 10-15), while it develops
before birth (around week 36-38). It is significantly developing the first two years after
birth. During adulthood, gyrification can happen which proves that the neurogenesis can
take place during adulthood and also the abilities can develop.

- The main gyri in the brain are the following:

a) The precentral gyrus:
→ It is a gyrus that comes anteriorly to the central sulcus. It is a part of the motor
cortex (part of the frontal lobe) that controls the voluntary movements. It is
located specifically posteriorly in the frontal lobe. It controls the movement of the
torso, arms, hands, fingers, and head.
b) The postcentral gyrus:
→ It is a gyrus that comes posteriorly to the central sulcus. It is part of the parietal
lobe. It includes a part of the somatosensory cortex which controls the sensation
of pain, touch, and temperature.
c) The superior temporal gyrus:
→ It is found on the top of the temporal lobe under the lateral sulcus. It includes
part of the auditory cortex that controls sound perception and recognizes different
frequencies and amplitudes. This gyrus includes wernicke's area in the left
hemisphere only. This area is responsible for language comprehension. This is
why the left hemisphere is more responsible for verbal activities than the right
hemisphere.

- The main sulci in the brain are the following:

a) The central sulcus:
→ It is a deep sulcus that separates the frontal lobe from the parietal lobe.
 b) The parieto-occipital lobe:
→ It separates the parietal lobe from the occipital lobe.
c) The lateral sulcus:
→ It separates the parietal lobe from the temporal lobe. This lobe is even called
the sylvian fissure.
d) The longitudinal fissure:
→ It is the deep sulcus that separates the two cerebral hemispheres of the
vertebral brain. It creates a sagittal section of the brain if we cut the brain
vertically through it.

- It is evident that the left side of the brain controls the right side of the body in the
movement of the muscles and sensation. The right side of the brain controls the left side
of the body. Beside the movement and sensation, it is evident that the right hemisphere
controls the skills, imagination, creativity, and emotions more than the left hemisphere
and the left hemisphere controls the verbal activities, quantities, numbers, logic, analysis,
and mathematics more than the right hemisphere. At the end, the connection between the
two hemispheres through the corpus callosum is the secret behind the balance in the
activities of the brain.

Parts of the brain:

- The main three parts of the brain are the cerebrum, cerebellum, and brainstem.

The brainstem:

- It is the part of the brain that connects the cerebrum of the brain to the spinal cord and
cerebellum.
- Generally, it is responsible for very vital functions including blood pressure, heart rate,
digestion, breathing, respiration, and sleep.
- 10 of the cranial nerves excluding the olfactory and optic derive from the brainstem.
- The brainstem is located inferiorly to the cerebrum, anteriorly to the cerebellum, and
superiorly to the spinal cord.
- The brainstem is divided into 3 main parts including the midbrain, pons, and medulla
oblongata.

1) The midbrain:
→ It is the first part of the brainstem closer to the cerebrum, It is between the thalamus
and pons, so it connects the pons to the diencephalon. It even connects the cerebrum to
the cerebellum. It includes the substantia nigra, an area that produces dopamine and is
related to parkinson’s disease.
 The midbrain is even named as mesencephalon (mesen means middle) → it derives and
differentiates from the middle part of the neural tube during embryonic development.
The midbrain does many functions related to its position and which cranial nerves derive
from it.

The main functions that midbrain deal with are:

1. Coordination of movement
2. Movement of eye dilation and constriction of the eye
3. Cardiovascular control
4. Behavior and defense response
5. Sensation of temperature and pain
6. Neck muscles movement
7. Related to sound localization (recognize the origin and sound )
8. Reward system

2) Pons : middle part in the brainstem between midbrain and medulla oblongata.
Main functions are:
1- sleep wake cycle
2- pain signal
3- works with cerebellum for movement balance
4- works with other parts of the brain for breathing

3) Medulla oblongata:
1- it manages heart rate, respiration, breathing, blood pressure (because the vagus
cranial nerve drives from it .
2-some autonomic responses like coughing, swallowing and vomiting .
3- it directly connects to the spinal cord

Cerebellum:

- Its first sized part of the brain

- Its located posteriorly in the brain under the occipital lobe
- Its divided into two hemispheres
- It has a cortex and center; it includes purkinje fibers that are characterized by having a lot
of branch dendrites which are related to movement coordination and emotions.
- The main functions for the cerebellum is voluntary movement coordination, balance,
posture and equilibrium
 - New studies relate cerebellum to behavior and emotion so could be related to addiction
and autism
- It doesn't initiate muscle contraction but it reviews the contraction and balances it so if
you need to ride a bike for example ,the motor cortex in the cerebrum initiates the
contraction while cerebellum makes sure that muscle contraction is balanced and
coordinated with the activity done.

Any damage in the cerebellum affects the fine and precise measurement balance of the body and
motor memory motor memory means to remember the movement needed to any certain activity
needs muscles.

Cerebrum:

- It is the largest part of the brain. It is responsible for most of the brain functions. It
controls hearing, vision, sensation, thinking, learning, creativity, emotions, personality…
- It is divided into 4 Lobes: Occipital, temporal, frontal and temporal.

1) Frontal Lobe: it is the anterior lobe of the cerebrum. It is responsible for the following
functions:

- Emotions
- Personality
- Working or short-term memory.
- Thinking.
- Language and speech production.
- Logic analysis.
- Voluntary muscle movement.
- Plan and organization.
- Attention and behavior.

Prefrontal cortex is the part of the cerebellum that controls the personality and working memory.

2) Parietal Lobe: Is the lobe found on the wall of the superior part of the cerebrum.

- It is responsible for sensation, pain signals, sense temperature and touch.

- It is also related to the distance judge and estimated size object.
- Make decisions and organize information.
- Sound processing.
 3) Temporal Lobe:

- Lateral lobe above the ear.

- Responsible for hearing perception. It includes the auditory cortex. So it processes
auditory information.
- It controls language comprehension.
- Recognize people and objects.
- Long term memory (semantic memory for facts) / Declarative memory (episodic memory
for events).
- It includes hippocampus and amygdala that both store long-term memory.

4) Occipital Lobe: The posterior lobe. Controls vision perception, color determination, and
recognizes shapes. Object and face recognition.

Reproductive system

Reproductive system is the body system which is responsible for reproduction. Reproduction is
the ability to produce new offsprings. In humans, reproduction is sexual, meaning it needs two
parents. Each parent produces a haploid cell called gamete. Haploid cell is the cell that contains
half of the number of chromosomes in a body cell. So the reproductive system does the
following functions:

1. Produce sex cells (gametes) egg in female and sperm in male

2. Produce sexual hormones needed to produce sex cells and have sexual characteristics
3. This system is also responsible for fertilization and pregnancy

Male Reproductive System

Male reproductive system does the following functions:

1. Produce Sperm Cells: sperm cells are produced in a process called spermatogenesis.
Spermatogenesis includes meiosis to produce haploid cells called spermatids and includes
maturation for these spermatids to become functional sperm cells (spermatozoa) that can
fertilize an egg. Normal adult male produces around 200-300 million sperm cells daily
after puberty.

2. Produce Sex Hormones (mainly testosterone): this hormone is necessary for

spermatogenesis and for all changes in characteristics with puberty like changes in the
voice, muscle mass, bone elongation, pubic hair, and etc.

3. Store and Transport sperm cells: this is why it includes ducts that can transport sperm
cells and includes glands that can form semen (a whitish fluid that is ejaculated out of
mailes’ body carrying sperm cells for fertilization).

- Male reproductive system includes primary organ which is testicles (testes) and
secondary organs includes ducts (epididymis, vas deferens, and urethra) and accessory
glands (prostate, seminal vesicles, and bulbourethral gland)

- Genitals are the external reproductive organs (penis and scrotum. Scrotum is a sac that
includes testicles, epididymis, and parts of vas deferens)

- Glands are the reproductive organs that can produce gametes (ovary in female and testicle
in male)

Testicles

- Each normal male has 2 testicles. The size of testicles start to develop after age 8 and
could reach a developed size in age 18 or before.

- Each testicle has a structure, size, and includes cells that help it to undergo
spermatogenesis and produce testosterone.

- The testicles are surrounded by a membrane called tunica. This membrane consists of an
external tunica called tunica vaginalis which consists of an outer layer called parietal
layer and inner layer called visceral layer. There is space between them filled by a fluid
for lubrication. The internal tunica is called tunica albuginea. Tunica is made up of
connective tissue and epithelial tissue.
- Inside each testicle, there are areas arranged beside each other. Each area is called lobule.
Inside each lobule there is a tubular structure called seminiferous tubules. It is the
functional unit of testicle where spermatogenesis and productional hormones take place.
There are around 500 seminiferous tubules in each testicle.

- If you take a cross section of seminiferous tubules, you will find it includes two areas,
germinal epithelium where the spermatogenesis takes place. It is where the germ cells
and sertoli cells are found, the other part in seminiferous tubule is the center of it, its
called lumen (where sperm cells are produced to be transported to epididymis for final
maturation)

- In seminiferous tubules, there are three types of cells that play an important role in
testicle. The cells are:

1. Germ Cells: they are the diploid cells which undergo meiosis to produce gamete
which develops into sperm cells. Germ cells undergo mitosis to have continues
reserver for spermatogenesis

2. Sertoli cells: are stored cells that help make sperm cells, they facilitate the
protection of sperm cells for spermatogenesis(PH, amino acid, ions, sugar...) they
act as testicle blood barriers that can connect testicles to blood for supply and
remove waste. Sertoli cells have receptors for a hormone needed to regulate
testicles function. It is FSH(follicle stimulating hormone) secreted by the anterior
pituitary gland. When FSH binds to its receptors on sertoli cells, sertoli cells
secrete androgen binding proteins that can bind to testosterone to concentrate and
accumulate in the germinal epithelium around germ cells to undergo
spermatogenesis.

3. Leydig cells:They are the source of testosterone. They are found in interstitial
tissue between seminiferous tubules. They are receptors to another anterior
pituitary hormone called LH (luteinizing hormone) .when LH binds to its
receptors on Leydig cells they produce and secrete testosterone. Testosterone
regulates spermatogenesis and it is released to the blood to affect other tissues on
the body like adipose tissue , muscles, bones, hair follicles, skin glands, brain, and
volatile cords.

- Hormonal activity in testicle and sperm production is regulated by hypothalamus and

pituitary gland hypothalamus secretes a hormone called GnRh (gonadotropin release
hormone). This hormone affects the anterior pituitary to release FSH and [Link]
 mechanism of how these hormones regulate spermatogenesis is called negative feedback
loop that maintains homeostasis.

- When Sperm count decreases due to ejaculation for example, sertoli cells secrete activin
that stimulate hypothalamus to release ore GnRh to release more FSH and LH from
pituitary [Link] binds to its receptors on sertoli cells to release androgen binding
proteins and LH binds to its receptors on Leydig cells to produce testosterone.

- If the rate of sperm production is high, sperm count increases sertoli cells release inhibin
which inhibits the hypothalamus to release GnRh reducing the activity of pituitary gland
to decrease release of PSH reducing FSH will decrease the rate of spermatogenesis.

- Male body produces estrogen from testosterone 10% in testicke and the rest are in
adispose tissue, skin and brain. Estrogen helps in having Libido( Sexdrive) and helps in
penis erection.

Scrotum:

- It is a pouch of skin that encloses a testicle with the epididymis and a part of the vas
deferens.

- It is made of skin and muscles.

- Testicles move down to the scrotum leaving the abdomen before birth late in embryonic
development. Having testicles inside the scrotum outside the abdomen helps in having
the proper temperature for spermatogenesis and keeping the testicle away from the
pressure of abdominal muscles which may affect the employing of sperm cells from the
testicle and epididymis.

- The scrotum includes the spermatic cord, which is a structure that includes a lot of blood
vessels and nerve endings. It surrounds the part of the vas deferens that is found in the
scrotum.

- The main functions of the scrotum is protection and maintaining temperature. The
temperature needed for spermatogenesis is 2-3 degrees less than the body temperature.

- The scrotum has some structures and mechanisms to maintain the temperature. It lacks
the subcutaneous layer (fat). It has scanty hair. It is rich with blood vessels (for dilation
and constriction0. It is rich with sweat glands. It has two muscles (cremaster muscle and
dartos muscle). If the trsticle’s temperature decreases and becomes cold, these muscles
 contract which moves the testicle close to the abdomen to decrease the scrotal surface
area to reduce heat loss. If the temperature increases, these muscles relax, moving the
testicle away from the body to increase the scrotal surface area to emit more heat.

Penis:

- It is one of the genitals where the urethra goes through for ejaculation.

- The penis needs to be erected for ejaculation to occur.

- The penis structure consists of a root that binds to the body by ligaments, the corpus or
body of the penis that includes spongy tissues, and the glans which is the outermost distal
part that that includes an opening called the meatus from where ejaculation takes place.

- The spongy tissues in the penis body are found in two areas: corpus spongiosum and
corpus cavernosum. These spongy tissues are cavities rich with a lot of blood vessels.

- During arousal, the blood flow increases toward these blood vessels so they will be filled
with a lot of blood. This is the reason for erection. So, the penis is not a muscular organ.

- The male is boring having foreskin that covers the glans of the penis. It is removed early
after birth by the religion to avoid infections in this area.

Ducts in the reproductive system: There are 3 ducts in the male reproductive system.

1) Epididymis: It is a very folded tube that binds directly to testicles. Sperm cells are
transported from testicles towards epididymis through channels between them called rete
testis.

- It is 6-7m long. The thickness of epididymis decreases while going away from testicle.
- Epididymis is divided into head, body and tail.
- The head of the epididymis is attached to the testicles. It is where the cytoplasm is
reduced in the sperm when the sperm cells reach epididymis, Its cytoplasm is diluted.
Epididymis reduces the cytoplasm increasing its concentration.
- The body of the epididymis is where the sperm is mature. The sperm leaves the body
motile, functional, mature and then can fertilize the egg cell.
- The tail of epididymis is where the sperm cells can be stored for around 12-13 days.
- Sperm cells stay in epididymis for around 2-4 weeks.
- So the function of the epididymis is to mature sperm cells and store them.
- The structure of a motile sperm:
 (The tail is made of flagellum)

- Acrosome is a membrane found in front of the sperm head. It includes hydrolytic

enzymes needed to break down the egg cell membrane to penetrate the egg.
- Acrosome undergoes acrosome exocytosis during penetration to release hydrolytic
enzymes.
- Epididymis may have an infection called epididymitis (infection in epididymis). Could
happen because of surgery in scrotum or STD (sexually transmitted diseases).

2) Vas deferens

- It is a fibromuscular duct or tube that transmits the sperm cells from epididymis toward
urethra for ejaculation.
- It is 35-40 cm in length.
- Sperm cells move through vas deferens by the contraction of smooth muscles in the wall
of Vas deferens and a fluid (not semen).
- The last part of vas deferens is called ampulla found posterior to bladder. Once sperm
cells reach ampulla, the seminal vesicle secretes 50-80% of semen. Vas deferens joins to
seminal vesicles and releases the semen in the ejaculatory duct. It is a small duct that
carries semen to urethra. Semen includes around 500 million sperm cells.

3) Urethra

- It is a muscular tube that runs out from the urinary bladder going through the prostate
gland (proximal part of urethra) and penis (distal part of urethra).
- Urthim is a common pathway between the urinary system and the reproductive system.
The male can't urinate and ejaculate at the same time.
- If the male ejaculates, the internal sphincter muscle in the neck of the bladder contracts.
To block the urine bladder.

Male reproductive accessory glands

- These glands are very essential to produce semen they are responsible for quality
semen.
 A) Seminal vesicle: it is part of the gland found posteriorly to the bladder. It contributes
50-80% of the semen. It secretes many substances, the total the main ones are:

1) Alkalines (Bases): Chemicals help to neutralize the acids in the urethra from
remaining urine and the acidity of the vagina in the female system. Sperm cells
carried by semen need a neutral environment PH 7-8.

2) Fructose: It is a source of energy that can provide sperm cells with energy for a
long time since the sperm cells can stay alive in the female reproductive system
for 3-5 days.

3) Prostaglandin: Chemical is secreted from different tissues in a body mainly

injured tissue. It is a hormone-like substance. This chemical is secreted also from
the membrane lining of the uterus to help in contractions during menstruation and
labor. This chemical can help promote the contraction of the vagina, cervix, and
uterus which helps move the sperm cell to fallopian.

4) Clotting Factors: The seminal vesicle secretes different clotting factors,

especially fibrinogen. Fibrinogen should be converted to fibrin to form the in clot.
Semen clots directly after ejaculation to protect the sperm cells in the female
body.

B) Prostate Gland:

- It is an essential gland found under the bladder

- It is essential for male fertility.
- It secretes very important substances like Zn and Ca+2→ Both are important for semen
liquefaction. Liquefaction is when semen becomes watery 15-20 min after ejaculation
inside the female's body to let sperm cells move. Zn and Ca+2 are also important for
acrosome exocytosis.
- Prostate Gland. Secretes very important enzymes needed. The first enzyme is needed for
semen clotting and the second enzyme is called PSAC( prostitute specific antigen) which
helps in liquefaction. It is a protease enzyme that helps break down a lot (fibrin).

C) Bulbourethral glands: It is pea-sized. Part of the gland is found under the prostate gland. It is
the least gland that affects fertility. It secretes some glycoproteins that function as lubricants.
And some alkaline to neutralize the remaining urine in the urethra.
The female reproductive system:-

- The female reproductive system does the following functions:

1) Sexual intercorse
2) Produce mature egg (ovum)
3) Ovulation (release the egg cell from the ovary)
4) Fertilization
5) Menstruation (blood flow out of the uterus if no fertilization occurs)
6) Fertilized egg implantation and development of embryo
7) Produce sex hormones

- The female reproductive system includes genitals (external parts which are called vulva,
like vaginal opening, clitoris, and labia)
- The internal organs of the system include the vagina, cervix, uterus, fallopian tube
(oviduct), and ovary.

1) Vagina:
→ It is a muscular canal that joins the cervix to the outside of the body. It has an
opening called the vaginal opening.
It widens to accommodate the baby during delivery, then it shrinks to go to its
normal width.
It is the pathway of menstruation and sexual intercorse as well.
It is lined with epithelial tissue with mucus membrane to help keep it moist.

- It can help in sexual pleasure since it is rich with nerve endings. When penis penetrates it,
it expands to prevent friction with penis.

- Vagina has its own microbiomes (bacteria lives in it).

- It can have self cleaning. These microbiomes are called vaginal flora. These bacteria
protect the vagina, from unwanted microbes like fungi. Flora undergo lactic acid
fermentation. To produce lactic acid and H2O2. These acids make the mucus in vagina
and cervix acidic for which is not suitable for many microbes to grow.

- Vaginitis is an infection in vagina. It may happen because of chemicals in soap or because

of dryness in the vagina. The dryness may happen if there is imbalance in the hormones.
 2) Cervix

→ It is the lowest part of the uterus. It allows sperm cells to enter the uterus and it
allows menstrual blood to exit. It is a muscular canal. If the uterus contracts, the
cervix expands. This occurs during childbirth, during which the cervix dilates
from 3cm to 10cm. It expands less than 1cm monthly during menstruation.

The main functions cervix does include:

- Menstruation
- Pregnancy
- Fertility, during and after ovulation, the cervix secretes fluid that is less acidic and thinnes
to let sperm cells move easily.
- Delivery:it expands during childbirth
- Protects the uterus from objects and germs to enter

3) Ovary

- Ovary is a small oval shaped gland located on either side of the uterus. It's attached to the
uterus and wall of the pelvis by ligaments.

- The main functions of the ovary is to produce sexhormones (estrogen and

progesterone)and it controls the menstrual cycle and pregnancy.

- The size of a normal ovary depends on the age and it gets smaller by aging.

- If we take a cross section from ovary we will find 3 layers .The outer most layer consist
of epithelial cuboidal, then the middle layer is ovarian cortex which is connective tissue
where ovarian follicles are [Link] innermost layer is the medulla which contains blood
vessels, nerves and lymphatic vessels.

- The female is born having all germ cells she needs in her reproductive years; she is born
having around 2 million germ cells finished interphase or DNA replication; they are
called primary oocytes.

- When the female starts puberty she has only 300,000- 400,000 primary oocytes in her
two ovaries together.

- Each primary oocyte is surrounded by a fluid filled sac called the ovarian follicle.
 - In the beginning of the menstrual cycle during flow phase (the phase when blood flows
which extends to 5 or 6 days)the hormone FSH increases FSH is secreted from anterior
pituitary under the regulation of GnRh of hypothalamus.

- FSH travels with blood targeting the ovary (10 - 12 or more follicles are targeted) .Each
follicle includes one primary oocyte. It starts growing, increasing its size. All targeted
follicles fail to develop completely and they break down except one follicle between
dominant.
- The dominant follicle grows completely and develops the egg inside it by letting it
undergo meiosis I to become a haploid cell called secondary oocyte or ovum. This
development happens because of estrogen which is produced by the follicle itself and
helps to develop the egg. The increase in the level of estrogen is followed by an increase
in the level of LH. Estrogen travels with the blood targeting the hypothalamus to
stimulate the anterior pituitary to release LH. When LH reaches its peak it stimulates the
dominant follicle to release and ovulate the mature [Link] is called ovulation which
happens around day 14 of the menstrual cycle of its 28 days.

- After ovulation the remainder of the follicle becomes a body called corpus luteum.
corpus luteum starts producing both estrogen and progesterone which are needed
especially the progesterone to prepare the uterus to expected pregnancy by increasing the
thickness of the endometrium (inner lining of the uterus)

- After ovulation, the remainder of the Follicle becomes a body called Corpus luteum. Corpus
luteum starts producing both estrogen and progesterone which are needed, especially
progesterone, to prepare the uterus for expected pregnancy by increasing the thickness of the
endometrium (inner lining of the uterus).

- The ovulated egg stays in the Fallopian tube for around 12-24 hours waiting for a sperm to
fertilize it. If the egg is not fertilized it breaks down a few days after ovulation & then the corpus
luteum breaks down. So, both estrogen and progesterone decline significantly. → These changes
stop the further growth of the endometrium and then cause shedding in the endometrium. This
menstruation (blood flow) happens & is considered as the beginning of another cycle. (after 28
days)

4️ Fallopian Tube:

- It is a muscular duct also called oviduct that picks the

egg from the ovary and keeps it in the tube for
 fertilization and transports the fertilized egg to the uterus.

→ So its functions are:

1. Holding place for egg

2. Fertilization
3. Move fertilized eggs into the uterus.

- Fallopian tube is lined up internally by ciliated epithelial tissue that helps move the egg. The
epithelial tissue includes mucous membrane which helps move the egg as well. The duct wall
includes smooth muscle as well.

The oviduct is divided into 4 parts:

1. Infundibulum. The closest part of the tube to the ovary. It includes finger-like structures called
Fimbriae. When the egg is ovulated the dominant follicle ruptures and secretes chemicals to
stimulate these Fimbriae to extend and catch the ovulated egg, then the egg moves inside the
tube.
2. Ampulla → It is where the fertilization could happen.
3. Isthmus.
4. Intramural portion that connects the fallopian tube to the uterus.

5️ Uterus (womb): It is a muscular hollow, pear-shaped organ that is where the fetus develops and grows.

- Uterus connects to the vagina by cervix and it is connected to the fallopian tube through the
Intramural portion of the tube.

- Uterus is divided into 3 parts: Fundus, uterus body (corpus), and cervix.

- Fundus is the part of the uterus which joins to the fallopian tube.

- The corpus is the place where the fertilized egg implantation and embryo development take
place.

- If the ovulated egg was fertilized after ovulation by 12-24 hours, the egg should reach the uterus,
it takes 3 to 5 days to reach the uterus during these days the uterus is prepared by thickening of
its internal lining endometrium → this thickening happens because of estrogen and progesterone
hormones of Corpus. The fertilized egg undergoes slow cell division and movement through the
fallopian tube.
 - After, These 3-5 days, the fertilized egg becomes a hollow structure containing around
200-300 cells called a blastocyst.

- When a blastocyst enters the uterus it takes 2-3 days to attach and burrow itself in the
thick endometrium. This attachment is called implantation. Progesterone and estrogen are
needed to implant the blastocyst in the endometrium.

- Once the blastocyst is implanted, it stimulates the formation of placenta. The placenta is
an organ that grows in the uterus attached to the embryo by the umbilical cord. So, the
Placenta (Source of o2 and nitrations ) Starts to form 10-12 days after fertilization. Both
estrogen and Progesterone are needed to form the placenta. The placenta starts releasing a
hormone called HCG (pregnancy hormone). That helps inhibit the hormones ESH and
LH, especially in the first trimester of pregnancy. All progesterone estrogen and HCG
help increase the size of the uterus during pregnancy and help in embryonic development.

- The Corpus luteum stays releasing estrogen and progesterone until week 12 of pregnancy.
Then the placenta starts producing them and the corpus luteum breaks down.

- Layers of Uterus: THERE ARE 3 LAYERS IN THE WAll OF THE UTERUS

1) Outermost layer: Perimetrium consists of connective tissue and mesothelium (epithelial).

The fibers in the perimetrium help expand the uterus during pregnancy.
2) Myometrium: The middle layers of the uterine wall. It consists of muscular tissue
(smooth muscle helps in expansion during pregnancy). Muscles contract to expand the
cervix during menstruation and childbirth.
3) Endometrium: The innermost layer of the uterine wall thickens to prepare the uterus for
pregnancy. Blood flow increases significantly during this preparation and the cells
undergo mitosis to have more endometrial cells.

→ The main Function Of estrogen:

1) Regulate menstrual cycle.

2) Ovulation by increasing the level of LH
3) Develop egg cells in the follicle
4) In the uterus, it helps thicken the endometrium development of the placenta and
embryonic development
5) Estrogen causes sexual characteristics the female has with puberty like bone
health and growth, enlargement of the breast, and change in the shape of the
pelvis.
‫تم بحمد هللا اخرالمالحظات للبايو‬
Alhamdulillah last bio notes

Yayy (: (sarita)