Nervous Tissue and Neurophysiology Study Guide

Three Basic Steps of the Nervous System

The nervous system carries out its tasks in three basic functional steps to maintain homeostasis and respond to external stimuli:

• Step 1: Sensory Input (Sense Organs): Sense organs receive information regarding changes in the body and the external environment. This information is then transmitted as coded messages to the spinal cord and the brain.

• Step 2: Integration (Brain and Spinal Cord): The brain and spinal cord process this incoming information, relate it to past experiences, and determine what response is appropriate to the specific circumstances.

• Step 3: Motor Output (Brain and Spinal Cord): The brain and spinal cord issue commands to muscles and gland cells, which are the effectors that carry out the determined response.

Anatomical Subdivisions of the Nervous System

The nervous system is divided into two major anatomical subdivisions:

• Central Nervous System (CNS): Consists of the brain and the spinal cord.

• Peripheral Nervous System (PNS): Consists of all the nervous system components except the brain and spinal cord. It is composed of nerves and ganglia.

  • Nerve: A bundle of nerve fibers (axons) wrapped in fibrous connective tissue. Examples include spinal nerves and cranial nerves.

  • Ganglion: A knot-like swelling in a nerve where neuron cell bodies (somas) are concentrated.

Functional Divisions of the Peripheral Nervous System (PNS)

The PNS is divided into sensory and motor divisions, each further subdivided into somatic and visceral branches:

• Sensory (Afferent) Division: Carries sensory signals from various receptors to the CNS. This division informs the CNS of stimuli within or around the body.

  • Somatic Sensory Division: Carries signals from receptors located in the skin, muscles, bones, and joints.

  • Visceral Sensory Division: Carries signals from the viscera of the thoracic and abdominal cavities (e.g., heart, lungs, stomach, and bladder).

• Motor (Efferent) Division: Carries signals from the CNS to gland and muscle cells, which act as effectors to carry out the body's response.

  • Somatic Motor Division: Carries signals to skeletal muscles. This output produces muscular contractions as well as somatic reflexes, which are involuntary muscle contractions.

  • Visceral Motor Division (Autonomic Nervous System, ANS): Carries signals to glands, cardiac muscle, and smooth muscle. These responses are involuntary, and the system's receptors participate in visceral reflexes.

    • Sympathetic Division: Tends to arouse the body for action (e.g., accelerating heartbeat).

    • Parasympathetic Division: Tends to have a calming effect (e.g., slowing the heartbeat).

Fundamental Types of Neurons

Neurons are classified into three types based on their functional role:

• Sensory (Afferent) Neurons: Detect changes in the environment (stimuli) and transmit information to the brain or spinal cord.

• Interneurons (Association Neurons): These lie entirely within the CNS between sensory and motor pathways. Approximately $90\%$ of all neurons are interneurons. They process, store, and retrieve information.

• Motor (Efferent) Neurons: Send signals away from the CNS to muscle and gland cells (effectors) to carry out responses.

Fundamental Properties of Neurons

Neurons possess three universal properties that enable communication:

• Excitability (Irritability): They are highly responsive to stimuli.

• Conductivity: They are capable of producing traveling electrical signals.

• Secretion: When an electrical signal reaches the end of a nerve fiber, a chemical neurotransmitter is secreted to cross the gap to the next cell.

Structure of a Neuron

A typical neuron consists of several specialized regions:

• Soma (Cell Body): Contains the nucleus and nucleolus.

• Dendrites: Branch-like structures that receive incoming signals.

• Axon (Nerve Fiber): A long process that carries signals away from the soma. It begins at the axon hillock.

• Initial Segment: The beginning of the axon.

• Trigger Zone: Comprised of the axon hillock and initial segment; this is where the action potential is generated.

• Axon Collateral: Branches of the axon.

• Terminal Arborization: Specialized endings at the distal end of the axon.

• Synaptic Knobs: Enlarged endings of the terminal arborization that contain synaptic vesicles.

• Myelin Sheath: An insulating layer around the axon.

• Nodes of Ranvier: Gaps in the myelin sheath.

• Internodes: Myelin-covered segments between the nodes.

• Schwann Cell: The cell that forms myelin in the PNS.

Variations in Neuronal Structure

Neurons are classified by the number of processes extending from the soma:

• Multipolar Neuron: Possesses one axon and multiple dendrites. This is the most common type and Includes most neurons in the brain and spinal cord.

• Bipolar Neuron: Possesses one axon and one dendrite. Found in olfactory cells, the retina, and the inner ear.

• Unipolar Neuron: Features a single process leading away from the soma. These are typically sensory neurons carrying signals from the skin and organs to the spinal cord.

• Anaxonic Neuron: Has many dendrites but no axon. These cells help in visual processing.

Neuroglia (Supportive Cells)

There are approximately $1 \times 10^{12}$ (1 trillion) neurons in the nervous system. Neuroglia (glial cells) outnumber neurons by as much as $50:1$.

• General Functions: Support and protect neurons, bind neurons together, form a framework for nervous tissue, and guide migrating neurons in fetuses.

• Synaptic Isolation: Glial cells cover mature neurons that are not in synaptic contact, preventing neurons from touching and providing precision to conduction pathways.

The Six Types of Neuroglial Cells

In the Central Nervous System (CNS):

1. Oligodendrocytes: Form myelin sheaths in the CNS by wrapping processes around multiple nerve fibers.

2. Astrocytes: The most abundant and diverse glial cells. Protoplasmic astrocytes contribute to the blood-brain barrier, secrete nerve growth factors, and regulate tissue fluid composition. Fibrous astrocytes form the framework of the CNS.

3. Ependymal Cells: Line cavities of the brain and spinal cord; they produce cerebrospinal fluid (CSF).

4. Microglia: Small macrophages formed from monocytes. They concentrate in areas of infection, trauma, or stroke to perform phagocytosis.

In the Peripheral Nervous System (PNS):

5. Schwann Cells: Produce the myelin sheath around nerve fibers in the PNS.

6. Satellite Cells: Surround and insulate the neurosomas in PNS ganglia.

Brain Tumors and Gliomas

Tumors are masses of rapidly dividing cells. Since mature neurons have little to no capacity for mitosis, brain tumors rarely arise from neurons themselves.

• Origins: Most brain tumors arise from the meninges (protective membranes), metastasis from other organs, or glial cells (which are mitotically active throughout life).

• Gliomas: Malignant brain tumors that grow rapidly. They are difficult to treat with chemotherapy because of the blood-brain barrier; treatment usually involves radiation or surgery.

Myelin and Myelination

Myelin is an insulating layer around a nerve fiber composed of the plasma membrane of glial cells ($20\%$ protein and $80\%$ lipid).

• Production: Formed by Schwann cells in the PNS and oligodendrocytes in the CNS.

• Myelination Process: Begins at week 14 of fetal development, proceeds rapidly during infancy, and is completed in late adolescence. Dietary fat is critical for proper CNS development during these stages.

• PNS Structure: Includes the neurilemma (the outermost layer of the Schwann cell, containing its nucleus and cytoplasm), the axolemma (axon membrane), and axoplasm (axon cytoplasm). The endoneurium is the external connective tissue layer.

• Unmyelinated Axons: In the PNS, even unmyelinated fibers are held in grooves on the surface of Schwann cells, but with only one membrane wrapping rather than multiple layers.

Diseases of the Myelin Sheath

• Multiple Sclerosis (MS): Oligodendrocytes and myelin sheaths in the CNS degenerate and are replaced by hardened scar tissue. This disrupts nerve conduction, leading to double vision, blindness, speech defects, tremors, and numbness. Onset usually leads to death within $10$ to $32$ years. The cause is unknown but may be autoimmune.

• Tay-Sachs Disease: A hereditary disorder primarily seen in infants of Eastern European Jewish ancestry. It involves the abnormal accumulation of a glycolipid in the myelin sheath. Symptoms include blindness, loss of coordination, and dementia. It is fatal by age $3$ to $4$.

Speed of Nerve Signals

The speed of signal transmission along a nerve fiber depends on the diameter of the fiber and the presence/absence of myelin.

• Surface Area: Large fibers have more surface area for signal conduction.

• Speed Variations:

  • Small, unmyelinated fibers: Up to $2.0\,m/sec$.

  • Small, myelinated fibers: Up to $15.0\,m/sec$.

  • Large, myelinated fibers: Up to $120\,m/sec$.

• Functional Distribution: Slow signals supply the stomach and dilate the pupil; fast signals supply skeletal muscles and transport sensory information for vision and balance.

Regeneration of Peripheral Nerve Fibers

Peripheral nerve fibers can regenerate if the soma is intact and at least some neurilemma remains.

1. Injury: The fiber is severed.

2. Degeneration: The segment distal to the injury degenerates (Wallerian degeneration). Macrophages clean up debris.

3. Early Regeneration: The soma swells, the ER breaks up, and the axon stump sprouts growth processes. A regeneration tube is formed by Schwann cells and the neurilemma.

4. Late Regeneration: The regeneration tube guides the growing sprout back to the original target cell.

5. Regenerated Fiber: The fiber is re-established, and the target muscle (which may have atrophied) regrows.

Electrical Potentials and Currents

Neuronal communication is based on electrophysiology. The Neuron Doctrine states that the nerve pathway is a series of separate cells rather than a continuous wire.

• Electrical Potential: A difference in the concentration of charged particles between different parts of the cell.

• Electrical Current: The flow of charged particles (ions) from one point to another.

• Resting Membrane Potential (RMP): Living cells are polarized, with an RMP of $-70\,mV$. More negatively charged particles reside on the inside of the membrane.

Maintaining the Resting Membrane Potential

RMP is maintained by unequal electrolyte distribution between the Extracellular Fluid (ECF) and Intracellular Fluid (ICF):

• Ion Concentration: Na+ is higher in ECF ($145\,mEq/L$) vs ICF ($12\,mEq/L$). K+ is higher in ICF ($150\,mEq/L$) vs ECF ($4\,mEq/L$).

• Permeability: The membrane is very permeable to K+ (it leaks out) but much less permeable to Na+.

• Anions: Large cytoplasmic anions (phosphates, sulfates, proteins) cannot escape the cell, contributing to the negative internal charge.

• $Na^+/K^+$ Pump: Maintains the gradient by pumping out $3\,Na^+$ for every $2\,K^+$ it brings in. This process requires significant ATP, necessitating constant glucose and oxygen supply to nerve tissue.

Local Potentials

Local potentials are short-range changes in voltage that occur when a neuron is stimulated by chemicals, light, heat, or mechanical disturbance.

• Mechanism: Stimulation opens Na+ gates, allowing Na+ to rush into the cell. This neutralizes some internal negative charge, shifting the voltage toward zero (depolarization).

• Properties of Local Potentials:

  • Graded: They vary in magnitude based on stimulus strength.

  • Decremental: They get weaker the farther they spread from the point of stimulation.

  • Reversible: If stimulation ceases, the cell returns to RMP.

  • Excitatory or Inhibitory: Some neurotransmitters (like glycine) hyperpolarize the membrane, making it more negative and less likely to fire.

Action Potentials

Action potentials are more dramatic voltage changes produced by voltage-regulated ion gates in the plasma membrane. They only occur where there is a high density of these gates.

• Gate Density: The soma has only $50$ to $75$ gates per $\mu m^2$ and cannot generate an action potential. The trigger zone has $350$ to $500$ gates per $\mu m^2$.

• The "Spike" Process:

  1. Local potential reaches the trigger zone.

  2. If it reaches the threshold (typically $-55\,mV$), voltage-gated Na+ channels open.

  3. Depolarization: Na+ enters the cell, shifting the voltage to $+35\,mV$.

  4. At peak voltage, Na+ gates close and K+ gates fully open.

  5. Repolarization: K+ leaves the cell, bringing the voltage back toward the negative.

  6. Hyperpolarization: K+ gates stay open slightly longer, making the cell more negative than RMP before returning to $-70\,mV$.

• Characteristics:

  • All-or-None Law: If threshold is reached, the neuron fires at maximum voltage; if not reached, it does not fire at all.

  • Nondecremental: Do not get weaker with distance.

  • Irreversible: Once started, they go to completion.

The Refractory Period

During and immediately after an action potential, a region of the neuron is resistant to further stimulation:

• Absolute Refractory Period: No stimulus of any strength will trigger a new action potential. This lasts from the start of the action potential until the return to RMP.

• Relative Refractory Period: Only an especially strong stimulus will trigger a new action potential, as K+ gates are still open and opposing the effect of incoming Na+.

Impulse Conduction

• Unmyelinated Fibers: Possess voltage-gated channels along their entire length. The signal is a chain reaction of action potentials traveling at $2\,m/sec$. It only travels away from the soma due to the refractory period behind it.

• Myelinated Fibers (Saltatory Conduction): Na+ inflow at a node creates an electrical field that diffuses fast but decrementally under the myelin to the next node. At the next node, the signal is strong enough to open new voltage-gated channels. The signal appears to "jump" from node to node.

Synapses and Neurotransmitters

• Presynaptic Neuron: Releases the neurotransmitter.

• Postsynaptic Neuron: Responds to the neurotransmitter.

• Synapse Locations: Can be axodendritic, axosomatic, or axoaxonic.

• Synaptic Cleft: A $20$ to $40\,nm$ gap between neurons.

• Discovery: Otto Loewi (1921) demonstrated chemical neurotransmission using frog hearts. He stimulated the vagus nerve of one frog (slowing its heart), transferred the saline to a second frog's heart, and found it also slowed. He called this "vagus substance," later identified as Acetylcholine.

Major Categories of Neurotransmitters

1. Acetylcholine (ACh)

2. Amino Acids: GABA, Glycine, Aspartic acid, Glutamate.

3. Monoamines: Catecholamines (Epinephrine, Norepinephrine, Dopamine), Histamine, Serotonin.

4. Neuropeptides: Chains of amino acids such as Substance P, Enkephalins, and $\beta$-endorphin.

Synaptic Transmission Mechanisms

• Synaptic Delay: The $0.5\,ms$ time required for signal arrival and the beginning of the postsynaptic action potential.

1. Excitatory Cholinergic Synapse

Uses Acetylcholine. Nerve signal opens voltage-gated Ca2+ channels, triggering ACh release. ACh binds to receptors, opening Na+ channels and producing a local potential. If the threshold of $-55\,mV$ is reached, an action potential is triggered.

2. Inhibitory GABA-ergic Synapse

Uses $\gamma$-aminobutyric acid. GABA receptors are chloride channels. Cl- enters the cell, hyperpolarizing it (making it more negative) and making the postsynaptic neuron less likely to fire.

3. Excitatory Adrenergic Synapse

Uses Norepinephrine (NE). Acts through a second-messenger system (cyclic AMP). The receptor is a transmembrane protein associated with a G protein. This system is slower but allows for enzyme amplification, where one NE molecule produce many product molecules.

Cessation of the Signal

• Diffusion: Neurotransmitter moves away into the ECF.

• Reuptake: Synaptic knob reabsorbs amino acids and monoamines (broken down by monoamine oxidase).

• Degradation: Acetylcholinesterase (AChE) breaks down ACh in the cleft; choline is recycled.

Neural Integration

Integration is the ability for neurons to process, store, and recall information based on postsynaptic potentials:

• Excitatory Postsynaptic Potentials (EPSP): Positive voltage changes (usually Na+ inflow). Glutamate and aspartate are excitatory.

• Inhibitory Postsynaptic Potentials (IPSP): Negative voltage changes (usually Cl- inflow or K+ outflow). Glycine and GABA are inhibitory.

• Summation: The process of adding up many EPSPs to reach threshold. Temporal summation occurs when a single synapse receives many EPSPs in rapid succession.

• Neural Coding:

  • Qualitative info: Depends on which neurons fire.

  • Quantitative info: Depends on stimulus strength. Stronger stimuli cause a more rapid firing rate or excite more neurons (recruitment).

Memory and Synaptic Plasticity

The physical basis of memory Is a pathway of cells called a memory trace (engram). Synaptic plasticity refers to the ability of synapses to be modified.

• Immediate Memory: Holds information for a few seconds; provides a sense of the flow of events.

• Short-term Memory: Lasts seconds to hours. Working memory allows us to keep information long enough to take action (e.g., dialing a phone).

  • Tetanic Stimulation: Rapid signals cause Ca2+ accumulation, making the cell more likely to fire.

  • Posttetanic Potentiation: Elevated Ca2+ levels allow for easier memory recovery (jogging the memory).

• Long-term Memory: May last a lifetime.

  • Declarative: Retention of facts as text/words.

  • Procedural: Retention of motor skills (e.g., typing).

  • Long-term Potentiation: Molecular changes including increased neurotransmitter receptors and protein synthesis for remodeling synapses.

Neurological Disorders

• Alzheimer Disease: Chronic memory loss, moody behavior, and loss of basic functions. Autopsy shows atrophy of gyri in the cerebral cortex, neurofibrillary tangles, and senile plaques. It involves a deficiency of ACh and nerve growth factors. It affects $11\%$ of population over 65 and $47\%$ by age 85.

• Parkinson Disease: Progressive loss of motor function (tremors, facial rigidity, slurred speech). Caused by the degeneration of dopamine-releasing neurons in the substantia nigra. Treatment includes dopamine precursors (L-dopa), MAO inhibitors (deprenyl), and surgery.