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Chapter 3. Neurophysiology

Highter category: 【Brain Science】 Brain Science Index

1. The characteristics of the brain

2. Neuron

3. Glia

4. Resting membrane potential

5. Graded potential vs Active potential

6. Generation of action potential

7. Conduction of active potential

8. Chemical synapse

9. Histology of cerebrum and cerebellum

10. Learning and memory

1. The characteristics of the brain

⑴ Immersed in cerebrospinal fluid within the skull and protected by three layers of meninges (pia mater, arachnoid mater, dura mater).

⑵ The human brain is composed of approximately 100 to 200 billion neurons.

① Number of neurons by species:

○ C. elegans (302)

○ Fruit fly (~150,000)

○ Zebrafish (~5 million)

○ Mouse (~71 million)

○ Zebra finch (~131 million)

○ Octopus (~500 million)

○ Marmoset (~636 million)

○ Rhesus macaque (~6.4 billion)

○ Human (~86 billion)

○ Elephant (~257 billion)

⑶ Supported by glial cells, which are about 10 times more numerous than neurons.

⑷ Human brain weight: about 2% of body weight (1,200–1,400 g).

⑸ Human brain volume: approximately 1,400 mL; in great apes, around 400 mL.

⑹ Metabolism: consumes about 20% of total oxygen and 20% of total blood flow.

⑺ The brain uses energy at a rate of 10 to 60 watts: approximately 0.1 nanowatts per neuron.

⑻ The brain uses only glucose as an energy source; if glucose is not continuously supplied, the brain’s glucose stores are depleted within 10 minutes

⑼ Staining techniques: Golgi, Nissl, Weigert

Figure 1. Staining techniques of brain sections; Golgi, Nissl, Weigert from left to right

2. Neuron

⑴ Structure of a Neuron

① Length: as short as 2–3 mm, or as long as about 1 m

② Cell body (soma)

○ Contains nucleus, ribosomes, endoplasmic reticulum, Golgi apparatus, mitochondria, etc.

○ The nucleus is located in the center, and within the center of it is a distinct nucleolus.

○ Rich in ribosomes, so it is stained by basic dyes.

○ Nissl body

○ Stained rough endoplasmic reticulum ribosomes and granular endoplasmic reticulum, appearing in a leopard-spot pattern.

○ The dye used for Nissl staining is a basic dye.

Figure 2. A cross-section of the spinal ganglion

The big, red-looking ones are ganglion cells

③ Dendrite: nerve parts branching like tree limbs

○ Not covered with myelin.

○ Receive information from other cells (postsynaptic).

○ Dendritic spines: increase surface area.

○ Excitatory neurons synapse with the spines; inhibitory neurons synapse with the shaft.

Figure 3. The dendrites of pyramid cells

Excitatory synapses are marked red and inhibitory synapses are marked blue

④ Axon (also called nerve fiber)

○ Covered with myelin.

○ Myelinated nerve: nerve covered with myelin.

○ Unmyelinated nerve: nerve without myelin (e.g., squid axon).

○ Length: up to 1–1.5 m.

○ Transmits information to other cells (presynaptic).

○ Axon collateral: a branch of the axon.

⑤ Nerve terminal (also called bouton or synaptic terminal)

⑵ Formation of Neurons

① Approximately 86 billion neurons exist; synapses number around 10¹⁴–10¹⁵.

② Neuronal growth and connection to target cells begin during embryonic development and are strengthened through learning and training.

③ Only some neurons can regenerate after injury: if neuronal debris or the cell body is absent, regeneration is not possible.

⑶ Classification of Neurons

① By function

○ Afferent neuron (sensory neuron): delivers information to the central nervous system through the dorsal region of the spinal cord.

○ Efferent neuron (motor neuron): transmits information from the central nervous system through the ventral region of the spinal cord.

○ Interneuron: connects afferent and efferent neurons.

② By presence of axon

○ Type I: with axon; generates action potential; includes motor and sensory neurons.

○ Type II: without axon; does not generate action potential; includes interneurons.

③ By presence of myelin sheath (Schwann cells)

○ Myelinated nerve: motor and sensory neurons in vertebrates.

○ Unmyelinated nerve: neurons in invertebrates, interneurons in vertebrates.

⑷ Types of Neurons

① Unipolar neuron:

○ Has dendrite and axon extending in one direction.

○ Found in invertebrates.

② Pseudo-unipolar neuron:

○ A single axon branches into two, functioning separately as dendrite and axon.

○ Example: sensory ganglion cells of the spinal ganglion.

③ Bipolar neuron:

○ Has one dendrite and one axon extending from the cell body.

○ Example: retinal cells, olfactory cells.

④ Multipolar neuron:

○ Has one axon and multiple dendrites extending from the cell body.

○ Example: most neurons.

Figure 4. Types of neurons

⑸ Patch Clamp Method

① A technique used to study electrophysiology by attaching a patch to the membrane of a living cell.

3. Glia

⑴ There are 1 trillion glia cells in an adult body.

① The etymology of “glia” is “glue”.

② Its full function hasn’t been revealed yet, but it is believed to play a very important role.

⑵ Astrocyte

① It is largest among glias.

② Class : Protoplasmic astrocyte, fibrous astrocyte

③ Location: Extends cytoplasmic processes that make contact on one side with blood vessels, and on the other side with neurons, the pia mater, and nerve fibers.

④ Function

○ Provides physical support.

○ Covers the nodes of Ranvier to prevent axonal exposure.

○ Reabsorbs excess potassium ions around neurons.

○ Absorbs glutamate and converts it into glutamine.

○ Maintains the blood-brain barrier (BBB) by forming tight junctions that block substance movement: The BBB can be understood as being formed by tight junctions in capillaries.

○ Acts as a stem cell, contributing to the formation of new neurons and glial cells.

⑶ Oligodendrocyte 

① Forms the myelin sheath of nerve fibers in the central nervous system.

② A single oligodendrocyte can myelinate multiple neurons.

Figure. 4. An oligodendrocyte in the CNS

⑷ Schwann cell 

① Forms the myelin sheath of nerve fibers in the peripheral nervous system (PNS).

② A single Schwann cell wraps around a single neuron multiple times.

⑸ Microglia

① Belong to the mononuclear phagocytic system and have phagocytic functions.

○ A type of macrophage (note: macrophages are also part of the mononuclear phagocytic system)

② Play a role in immune functions within the nervous system.

⑹ Ependymal cell

① Epithelial cells that line the inner surfaces of the central canal and brain ventricles.

② Possess cilia that contribute to the microcirculation of cerebrospinal fluid (CSF).

③ Tight junctions (part of the blood-brain barrier, BBB) exist between endothelial cells of blood vessels, limiting substance exchange between plasma and brain interstitial fluid.

Figure. 6. Various types of glia

4. Resting membrane potential

⑴ Membrane potential is the inner-membrane electrical potential relative to the outer-membrane electrical potential. (unit : ㎷)

⑵ The equilibrium states of resting membrane potential is -70 ㎷.

① An uneven distribution of ions around the cell membrane.

② The selective transparency of the cell membrane (Na⁺ < K⁺): Some K⁺ channels are open

③ Na⁺/ K⁺ pump : It moves 3 molecules of Na⁺ outside the cell and moves 2 molecules of K⁺ inside the cell.

④ The attractive force by the negative-charged proteins in the cell

⑶ Nernst Equation

① Derivation: G = −RT lnQ = −nFE

② Interpretation

When the concentration of ions is higher inside the cell than outside, an osmotic potential exists that drives ions outward.

Since the system is at equilibrium, there must be a counteracting force that pulls ions inward.

This opposing force is the electrical potential generated when the inside of the membrane is negatively charged (E < 0) and the outside is positively charged (E > 0).

For the same reasons described in section ⑵, this electric potential exists and maintains the asymmetry of the ion’s osmotic potential.

③ Applications

○ When K⁺ is added to the extracellular fluid, the K⁺ pump pumps K⁺ into the cell, resulting in an increase in resting membrane potential.

○ Note: If only K⁺ is present, adding more K⁺ does not affect the resting membrane potential.

○ The higher the concentration of external ions (e.g., Na⁺), the lower the membrane potential, leading to a decrease in action potential frequency.

○ The higher the concentration of internal ions (e.g., K⁺, as in hyperkalemia), the higher the threshold becomes, making action potentials easier to trigger.

○ Conversely, the lower the internal ion concentration (e.g., K⁺, as in hypokalemia), the lower the threshold becomes, leading to reduced action potential frequency.

⑷ Goldman-Hodgkin-Katz Equation

① The Nernst equation calculates the equilibrium potential when only one ion is involved.

② In reality, the actual membrane potential is influenced by the permeability (P) and distribution of multiple ions, each contributing differently depending on the cell membrane’s permeability to each ion.

③ Examples of Equilibrium Potentials:

○ E_K⁺ = −88 mV

○ E_Na⁺ = +53 mV

○ E_Ca²⁺ = +145 mV

○ E_Cl⁻ = −58 mV

④ The resting membrane potential tends to be close to the equilibrium potential of the ion with the highest electrical conductance.

5. Graded Potential vs Action Potential

⑴ Graded Potential (Stepwise Potential): The membrane potential changes in proportion to the influx of ions.

⑵ Action Potential: Always induces a membrane potential change of constant magnitude.

⑶ Magnitude: The farther it propagates, the smaller the magnitude becomes vs. the magnitude is always constant.

⑷ Channels: Ligand-gated channels vs. Voltage-gated channels.

① The total number of channels is greater at sites that generate action potentials.

⑸ Related Ions: Na⁺ (excitatory), K⁺, Cl^- (inhibitory) vs. Na⁺, K⁺.

⑹ Location: Dendrites, cell body of the neuron vs. axon.

① In the axon hillock, both graded potentials and action potentials are involved.

6. Generation of action potential

⑴ Law of All-or-None: Action potentials follow the all-or-none principle.

⑵ Channels

① Na⁺ channel: Has both activation gate and inactivation gate.

② K⁺ channel

③ Channel opening duration: Na⁺ channel < K⁺ channel

④ Channel opening speed: Na⁺ channel > K⁺ channel

⑶ 1^st. Resting State (Equilibrium State)

① Na⁺ channel: activation gate closed, inactivation gate open.

② K⁺ channel: closed.

⑷ 2^nd. Graded Potential

① When Na⁺ enters from a neighboring axon, a small number of voltage-gated Na⁺ channels open.

② Opened voltage-gated Na⁺ channels induce the opening of other closed voltage-gated Na⁺ channels.

⑸ 3^rd. Depolarization

① Threshold potential: -40 to -50 mV. Depolarization beyond this threshold is required for an action potential to occur.

② Na⁺ channel: activation gate open, inactivation gate closed.

③ K⁺ channel: closed.

⑹ 4^th. Falling Phase

① Na⁺ channel: activation gate open, inactivation gate closed (immediately after reaching +30 mV).

② K⁺ channel: just before reaching +30 mV, K⁺ efflux causes membrane potential to fall.

③ Astrocytes regulate the rate of K⁺ efflux.

⑺ 5^th. Repolarization

① Na⁺ channel: activation gate closed, inactivation gate closed.

② K⁺ channel: open.

③ Absolute refractory period present.

⑻ 6^th. Hyperpolarization

① Na⁺ channel: activation gate closed, inactivation gate open.

② K⁺ channel: in the process of closing

③ Slowly returns to -70 mV through mechanisms restoring the resting membrane potential

④ Relative refractory period present

⑼ Refractory Period

① Time during which K⁺ ions exit the axon and the membrane potential returns to -70 mV.

② Absolute refractory period: From the moment the membrane potential exceeds threshold until repolarization occurs

○ No action potential can be generated regardless of stimulus intensity

○ h-gate (inactivation gate) is closed

③ Relative refractory period: Beginning with hyperpolarization

○ h-gate (inactivation gate) is open, m-gate (activation gate) is closed.

○ A very strong stimulus can depolarize the membrane beyond threshold, opening the activation gate and generating an action potential

⑽ Action Potential Patterns Depending on Extracellular Na⁺ Concentration

⑾ Inhibitors

① Tetrodotoxin (TTX): Irreversibly inhibits voltage-gated Na⁺ channels.

○ Found mainly in the ovaries and liver of pufferfish.

○ Pufferfish themselves are resistant due to a mutation in their Na⁺ channel protein (just a single amino acid difference).

② Tetraethylammonium (TEA): Blocks voltage-gated K⁺ channels.

③ Botox: Inhibits voltage-gated Ca²⁺ channels at the neuromuscular junction → prevents acetylcholine release → causes muscle paralysis

④ CPZ: Reduces or inhibits neurotransmitter release.

7. Conduction of active potential

⑴ Local Current Mechanism: Depolarizes neighboring regions and forms a threshold potential, leading to regenerative conduction.

⑵ Unidirectional Conduction: The region where an action potential has occurred is in the refractory period, so conduction proceeds only in one direction.

⑶ Saltatory Conduction

① Myelination

○ Myelin is gradually formed until about one year after birth.

○ Oligodendrocytes: Extend processes that wrap around nearby nerve fibers to form myelin.

○ Schwann cells: The entire cell wraps itself around the nerve fiber to form myelin.

○ Myelin is formed as the axon is tightly wrapped in layers. This wrapping occurs when opposing cell membranes come into near contact, creating a double-membrane structure. The principal component of myelin is lipid, which is also the main constituent of cell membranes.

○ Because myelin is formed in this manner, gaps remain, known as the nodes of Ranvier.

② Myelin as an Insulator → Action potentials form only at unmyelinated regions → Conduction speed increases.

○ The time required for action potential generation equals the time for localized diffusion of sodium and potassium ions.

○ Axons are wrapped with insulating myelin to prevent action potentials from being generated at every segment.

③ Saltatory Conduction: The phenomenon in which action potentials “jump” from one node of Ranvier to the next.

○ At the nodes of Ranvier: Voltage-gated ion channels are present → active propagation.

○ Between the nodes of Ranvier: No voltage-gated ion channels → passive propagation.

○ Saltatory conduction occurs when the potential at the nodes of Ranvier reaches and maintains above threshold, generating an action potential.

⑷ Conduction Velocity

① 135 m/s

② The larger the nerve diameter, the faster the conduction speed.

③ In humans, a microcurrent of about 39 mA flows through the nerves.

8. Chemical synapse

⑴ Synapse

① Type 1: Electrical Synapse

○ Features: Bidirectional, gap junctions (connexons), very fast, narrow synaptic cleft

○ Examples: Cardiac muscle, central nervous system

② Type 2: Chemical Synapse

○ Features: Unidirectional, wide synaptic cleft, transmission through neurotransmitters.

○ Presence of voltage-gated Ca²⁺ channels (required for neurotransmitter release).

○ Neurotransmitters are removed by reuptake into presynaptic neurons.

○ Nicotinic receptor: Fast response, related to ion channel opening in postsynaptic neurons.

○ Muscarinic receptor: Slow response, related to second messenger signaling in postsynaptic neurons.

⑵ Mechanism of Chemical Synapse

① Neurotransmitters

Figure 10. Components of chemical synapse

⑶ Synthesis and Storage of Neurotransmitters: Stored in synaptic vesicles.

Figure 11. Synthesis and Storage of Neurotransmitters

⑷ Release of Neurotransmitters

① Ca²⁺ ions promote the binding of synaptic vesicles to the presynaptic neuron’s membrane.

② Neurotransmitters are released into the synaptic cleft.

③ Synaptic ribbon: Found in regions where Ca²⁺ influx is concentrated; facilitates neurotransmitter release by transporting vesicles.

Figure 12. Release of neurotransmitters through exocytosis

⑸ Postsynaptic Potentials

① Excitatory Postsynaptic Potential (EPSP): Na⁺ influx → depolarization

Figure 13. Excitatory Postsynaptic Potential (EPSP)

② Inhibitory Postsynaptic Potential (IPSP): K⁺ efflux or Cl^- influx → hyperpolarization

Figure 14. Inhibitory Postsynaptic Potential (IPSP)

③ Reversal Potential: A membrane potential at which no postsynaptic current (EPC) occurs.

⑹ Synaptic Integration

① Spatial summation and temporal summation

Figure 15. EPSP synapse summation

② Shunting inhibition

Figure 16. Shunting inhibition

⑺ Types of Neurotransmitters

① Acetylcholine (ACh): Choline + acetyl-CoA

○ Motor neurons (muscle): Excitatory

○ Autonomic nervous system: Excitatory; suppresses metabolism.

○ Parasympathetic nervous system: Excitatory or inhibitory; regulation of parasympathetic activity

○ Central nervous system: Excitatory

○ Invertebrates: Excitatory or inhibitory

○ Secretion process of ACh

Figure 17. Secretion process of ACh

○ Nicotinic ACh receptor (nAChR): Excitatory; observed in autonomic ganglia and neuromuscular junctions.

Figure 18. Nicotinic acetylcholine receptor

○ Muscarinic ACh receptor (mAChR): Excitatory or inhibitory; observed at parasympathetic nerve terminals.

Figure 19. Muscarinic acetylcholine receptor

○ Inhibitors/Toxins:

○ Botulinum toxin: Found in spoiled meat; blocks fusion of synaptic vesicles with the membrane.

○ Tetanus toxin: Found in Clostridium tetani; blocks vesicle fusion.

○ Muscarine: Found in poisonous mushrooms; interferes with ACh-receptor binding.

○ Najatoxin: Found in cobras; interferes with ACh-receptor binding.

○ Curare (d-tubocurarine): Blocks ACh-receptor binding.

○ Atropine: Blocks ACh-receptor binding.

○ ACh breakdown inhibitors: Sarin nerve gas, insecticides

② Epinephrine, Norepinephrine (Catecholamines):

○ Postganglionic sympathetic nerves: Excitatory or inhibitory; stimulate metabolism, increase heart rate.

○ Central nervous system: Excitatory or inhibitory; regulate sympathetic activity and immune responses.

③ Serotonin (Catecholamine):

○ CNS: Inhibitory; regulates appetite, cardiovascular function, sleep, concentration, and emotion

④ Dopamine (Catecholamine):

○ CNS or peripheral nervous system: Excitatory or inhibitory; regulates emotion and motor control

○ Deficiency: Schizophrenia (depending on the area, there is also an excess of dopamine), Parkinson’s disease (impaired motor integration)

⑤ Glycine (Amino acid):

○ Spinal cord: Inhibitory; suppresses excitation of motor neurons.

○ Example: African native poison darts inhibit glycine receptors → excessive spinal excitation → paralysis

⑥ Glutamate (Amino acid):

○ CNS: Excitatory; stimulates motor neurons, involved in learning and memory (LTP).

⑦ GABA (γ-aminobutyric acid, Amino acid):

○ CNS: Inhibitory; involved in cell signaling.

○ Deficiency: Loss of self-control, alcohol sensitivity, delusions

⑧ Endorphins (Peptides):

○ CNS: Excitatory or inhibitory; produce pleasure and suppress pain.

⑨ Enkephalins (Peptides):

○ CNS: Produce pleasure and suppress pain.

⑩ Histamine:

○ Certain regions of CNS: Arousal

⑪ Substance P

⑫ Nitric Oxide (NO)

⑬ Prostaglandins

9. Histology of cerebrum and cerebellum

⑴ In the servous system, neuronal cell bodies generally cluster together according to similar function:

① Basal ganglion

② Thalamus

③ Various types of nuclei

④ Gray matter of the spinal cord

⑤ Ganglion

⑵ Histological Structure of the Cerebrum

① General organization: Gray matter is located on the surface, white matter inside, and the cortex is subdivided into six layers.

○ Molecular layer:

○ Outermost layer of the cerebral cortex

○ Contains very few neurons.

○ Contains nerve fibers running parallel to the brain surface.

○ External granular layer:

○ Contains granule cells and glial cells.

○ This layer primarily receives signals from outside.

○ External pyramidal layer:

○ Contains pyramidal-shaped pyramidal cells.

○ This layer mainly sends signals outward.

○ Internal granular layer:

○ Densely packed small granule cells

○ Internal pyramidal layer:

○ Contains the largest pyramidal cells.

○ Multiform layer:

○ Contains cells of various shapes.

② Column Theory

○ Proposed by Hubel.

○ Granular layers receive input signals, pyramidal layers send output signals.

○ Continuous communication between adjacent layers allows for complex information processing.

○ Thus, the cells within each column are considered functionally integrated.

Figure 20. The cross section representing the 6 layers of cerebral cortex

⑶ Histological Structure of the Cerebellum

① Cerebellar physiology

○ The cerebellum contains the largest number of neurons in the brain.

○ Rich in inhibitory neurons, allowing for fine motor control.

② Gray matter on the surface, white matter inside, subdivided into three layers.

③ Molecular layer

○ Outermost layer of the cerebellar cortex

○ Cells are loosely arranged.

④ Purkinje cell layer: very large Purkinje cells arranged in rows between the molecular and granular layers.

⑤ Granular layer: densely packed with neurons.

Figure 21. The picture representing 3 layers of cerebellar cortex

Figure. 22. The tissue picture with special dying representing purkinje cells in cerebellar cortex

It shows dendrites well and the arrow represents an axon.

10. Learning and memory

⑴ History

① Eric R. Kandel received the Nobel Prize.

② Used the sea slug (Aplysia) as a model → neurons are large, allowing morphological study.

⑵ Long-Term Potentiation (LTP): Occurs in the hippocampus, related to Hebb’s law.

① Molecular Mechanism

Figure 23. Molecular Mechanism of LTP

○ 1^st. The stimulated presynaptic neuron releases glutamate.

○ 2^nd. Glutamate binds to AMPA receptors on the postsynaptic membrane.

○ 3^rd. AMPA receptors open, Na⁺ enters, and depolarization occurs; depolarization in the postsynaptic neuron is proportional to the stimulus.

○ 4^th. When strong depolarization occurs in the postsynaptic neuron, Mg²⁺ blocking the NMDA receptor channel is removed (in the presence of glutamate).

○ 5^th. NMDA receptors open, leading to Ca²⁺ influx, increasing intracellular Ca²⁺ concentration in the postsynaptic neuron.

○ 6^th. Ca²⁺ acts as a second messenger, increasing NO synthase activity and generating nitric oxide (NO).

○ 7^th. NO increases the number of AMPA receptors in the postsynaptic membrane.

○ 8^th. NO additionally acts as a retrograde messenger, diffusing back to the presynaptic neuron.

○ 9^th. The presynaptic neuron releases more glutamate.

② Synaptic Changes: Positive feedback mechanism.

③ Functional Changes: Strengthened synaptic transmission.

Figure 24. Functional Changes of Postsynaptic Neurons according to LTP

⑶ LTD(long-term depression): It takes place at the cerebellum.

① Molecular mechanism

Figure 25. A mechanism of LTP/LTD

② Synaptic Changes

Figure 26. AMPA receptor phosphorelation by PKC and subsequent LTD

③ The learning and memory in the cerebellum

○ The cerebellum is one-tenth of the cerebrum in size but is equal in the number of neurons.

○ Input: PF(parallel fiber), CF(climbing fiber); It represents address.

○ Output: PC(purkinje cell); There is the change of synaptic strength.

Figure 27. Circuit diagram of cerebellum neurons

Figure 28. Circuit diagram of cerebellum neurons

Input: 2018.09.17 23:53