Nervous Tissue – Complete Study Notes

Overview of the Nervous System

Neurons have 3 fundamental physiological properties that enable them to communicate with other cells:

• 1. Excitability: all cells are excitable- they respond to stimuli. Neurons exhibit this property to the highest degree

• 2. Conductivity: neurons responds to stimuli by producing electrical signals that are quickly conducted to other cells at distant locations

• 3. when the signal reaches the end of an axon, the neuron secretes a neurotransmitter that crosses the gap and stimulates the next cell

• Two body-wide control systems coordinate and integrate physiology

  • Endocrine system: blood-borne hormones

  • Nervous system: rapid electrical & chemical signaling via neurons

• General three-step information flow

  • 1️⃣ Sensory input: receptors → CNS

  • 2️⃣ Integration: CNS analyzes & decides response

  • 3️⃣ Motor output: CNS → effectors (muscles/glands)

• Anatomical divisions

  • Central Nervous System (CNS): brain + spinal cord performs most of decision making functions

  • Peripheral Nervous System (PNS): nerves + ganglia

    • Nerve = bundle of axons in CT sheath

    • Ganglion = knot-like swelling housing neuron cell bodies of PNS are concentrated somata

• Functional divisions of PNS (divided into sensory and motor divisions each with somatic and visceral subdivisions)

  • Sensory (afferent): collects and sends signals from receptors to the central nervous system

    • Somatic sensory: focuses on skin, muscles, bones, joints

    • Visceral sensory: deals with internal organs like thoracic & abdominal viscera (heart and lungs)

  • Motor (efferent): carries signals from the CNS mainly to gland and muscle cells that carry out body’s response

    • Effector: cells and organs that respond to these signals

  • Somatic motor: skeletal muscle (voluntary & reflex)

    • Visceral motor = Autonomic Nervous System (ANS)carries signals to glands, cardiac and smooth muscle with no voluntary control over these effectors)

      • Sympathetic: alertness, HR, BP (“fight-or-flight”)

      • Parasympathetic: calming, digestion, energy storage (“rest-and-digest”)

      • Enteric plexus: intrinsic GI tract network coordinating motility/secretions

        • has more neurons than spinal cord, for different regions of long intestine to communicate & coordinate their motility & secretion.

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Universal Properties of Neurons

• Excitability (irritability): react to stimuli

• Conductivity: propagate electrical signals along membrane

• Secretion: release neurotransmitter at synapse when signal arrives

Functional Classes of Neurons

• Sensory (afferent): receptor → CNS

• Interneurons (association): entirely within CNS, \approx 90\% of neurons; integrative “decision makers”

• Motor (efferent): CNS → effectors

Structural Anatomy of a Neuron

• Cell body (soma / neurosoma / perikaryon)

  • Nucleus-nucleolus being iste of rRNA synthesis and ribosome assembly, Nissl bodies (segmented RER darkly stained regions), mitochondria, Golgi, lysosomes

  • Cytoplasm: chromatophilic substance-free ribsosomes and rough ER

  • Cytoskeleton: microtubules + neurofibrils; lack centrioles ⇒ no mitosis post-adolescence

  • Inclusions: glycogen granules, lipid droplets, melanin, lipofuscin

• Neurites (processes reaching out to other cells are classified into two types: axons, which transmit signals away from the cell body, and dendrites, which receive signals from other neurons )

  • Dendrites: 1 – thousands; receive input; more dendrites = more information capacity (bare branches of a tree). Primary site for receiving signals

  • Body (soma): mitochondria, nucleus, rough endoplasmic reticulum

  • Axon (nerve fiber): single, long; originates at axon hillock carries impulses away from cell body; sends the output

  • Axoplasm, axolemma: cytoplasm of the axon; axolemma is the plasma membrane surrounding the axon that plays a crucial role in the conduction of nerve impulses. The axon also contains essential organelles and structures such as mitochondria and neurofilaments that support its function and integrity, ensuring efficient signal transmission throughout the nervous system.

  • Neurolemmocytes: form myelin around PNS axon with a neruolemmocyte nucleus forming myelin sheath

    • Myelin sheath: insulating covering around some axons greatly increasing speed of axon signal

  • myelination: a process where axons are wrapped in a myelin sheath, which insulates them and significantly increases the speed of electrical signal conduction. This sheath is formed by glial cells, such as oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system, providing both protective and supportive functions.

  • Nodes of Ranvier: gaps in the myelin sheath that facilitate rapid signal propagation through saltatory conduction, allowing impulses to jump from one node to the next, greatly enhancing conduction speed.

  • Synapse: a specialized junction where axons connect with other neurons or target cells with a synaptic cleft, enabling the transmission of nerve impulses through neurotransmitter release, playing a pivotal role in communication within the nervous system.

    • Axon of presynaptic neuron

    • synaptic knob

    • synaptic cleft

    • neurotransmitter→ dendrite of postsynaptic neuron.

  • Neurotransmitters: chemical messengers released from synaptic vesicles at the synapse that bind to specific receptors on the post-synaptic membrane, initiating a response in the target cell and influencing neuronal communication and signal propagation.

  • Action Potential: a rapid change in membrane potential that occurs when a neuron sends a signal along its axon, characterized by depolarization followed by repolarization, which is essential for the transmission of signals across neurons.

  • Resting Potential: the electrical potential difference across the neuronal membrane when a neuron is not actively sending a signal, created by the distribution of ions (such as sodium and potassium) and maintaining the readiness of the neuron to fire an action potential.

  • 
    

  • Terminal arborization ending in synaptic boutons forming synapses

• 

  Structural neuron types

  • Multipolar: 1 axon + many dendrites (most CNS neurons)

  • Bipolar: 1 axon + 1 dendrite (retina, olfactory epithelium, inner ear)

  • Unipolar (pseudounipolar): single process that splits into peripheral & central axonal branches (sensory ganglia)

  • Anaxonic: dendrites only; no axon (retina, brain, adrenal medulla)

Multipolar neurons

Bipolar Neurons

Unipolar: involved in the senses of touch and pain

Anaxonic Neuron- Amacrine cell of retina

Axonal Transport

• Bidirectional movement along microtubules via motor proteins

  • Anterograde (soma → axon terminal): kinesin; supplies enzymes, vesicles, organelles. Movement away from cell body, down axon, driven by kinesin

  • Retrograde (terminal → soma): dynein; returns used vesicles, informs soma, can carry pathogens (e.g., rabies). Movement up the axon toward the cell body driven by motor protein dynein

• Speed categories

  • Fast: 200\text{–}400\,\text{mm/day} (both directions)

    • fast anterograde transport of organelles, enzymes, synaptic vesicles, small molecules

    • fast retrograde transport for recycled materials, some pathogens

  • Slow: 0.2\text{–}0.5\,\text{mm/day} anterograde only; “stop-and-go”; governs regeneration rate

    • Transport of enzymes, cytoskeletal components, new axoplasm

    • Damaged nerves regenerate at a speed governed by slow axonal
      transport, which is critical for restoring functionality and repairing the nerve pathways.

Neuroglia (Supporting protecting Cells that help neurons function)

• ~ 86 \text{ billion} neurons in adult brain & a comparable number of glia 1:1 ratio of glial cells to neurons

  • Bind neurons together

  • Form supportive tissue framework

  • In fetus, guide migrating neurons to their destination

  • Cover mature neurons (except at synapses)
    • Prevents neurons from touching each other
    • Gives precision to conduction pathways

• 4 types of CNS glia:

  • Oligodendrocytes: myelin sheaths; can myelinate multiple axons produces myelin

  • Ependymal cells: line ventricles, cavities of the brain and spinal cord; secrete & circulate CSF (ciliated)

  • Microglia: immune surveillance; phagocytize debris & microbes, dead nervous tissue

  • Astrocytes (most abundant)

    • Structural framework, perivascular feet induce \text{BBB} (blood-brain barrier)

    • Regulate blood flow by attaching to capillary bringing oxygen, and diffuse or filter into neuron , & neurotransmitter uptake, release lactate for energy, secrete nerve growth factors, influence synaptic signaling, regulate composition of tissue fluid

    • Repair scarring (astrocytosis / sclerosis)

• 

  Peripheral (PNS) glia cells, found only in peripheral nervous system

  • Schwann cells (neurolemmocytes): form neurilemma around all PNS fibers and myelin envelop axons of PNS, form myelin in PNS; aid regeneration of damaged fibers

  • Satellite cells: surround somata in ganglia; electrical insulation & chemical regulation

• Clinical note: Gliomas—malignant tumors from glia grow rapidly; BBB blocks chemo ⇒ treated with surgery/radiation

• Brain tumors arise from:

  • meninges (protective membranes of CNS)

  • Metastasis from nonneuronal tumors in other organs

  • Glial cells that are mitotically active throughout life

Myelin Sheath

• spiral layers of insulation around an axon

• Formed by Schwann cells in PNS, oligodendrocytes in
  CNS

  • 20 % protein, 80 % lipid (high insulation value)

• Production of sheath is called myelination

  • Begins during fetal development, proceeds rapidly during
    infancy, complete by late adolescence

• PNS myelination (Schwann cell) production of sheath

  • Cell winds repeatedly around one internode; outermost layer = neurilemma (contains nucleus & cytoplasm)

  • External basal lamina + endoneurium CT

• Myelination

  

  CNS myelination (oligodendrocyte)

  • Each process wraps part of several axons; no neurilemma or endoneurium; spiral inward

  • During myelination, nucleus cannot migrate around the
    axon like a Schwann cell does

    • Must push newer layers of myelin under the older ones, so
      myelination spirals inward toward axon

    • No neurilemma

• Segmentation terminology for both PNS and CNS, myelin sheath is segmented

  • Many Schwann cells (PNS) or oligodendrocytes (CNS) are
    needed to myelinate one axon

    • Each segment of axon wrapped by different glial cell

  • Myelin sheath gap (node of Ranvier)—gap between
    segments

  • Internode segments: myelinated segment encircled by schwann cells

  • Initial segment—bare section of axon between the axon
    hillock and the first glial cell: Initial segment + axon hillock = trigger zone

  • Node of Ranvier: gap between myelin sheaths (voltage-gated channel hot-spot) where conduction/repolarization is conducted on axon making it faster since it doesn’t have to go through the internode segments

• Demyelinating diseases

  • Multiple Sclerosis: autoimmune oligodendrocyte destruction ⇒ plaques, conduction block, adult onset

  • Tay–Sachs: hereditary GM2 ganglioside accumulation in myelin ⇒ neural dysfunction, fatal by age 4

Unmyelinated Axons & Conduction Speed

• PNS: one Schwann cell envelopes several axons in surface grooves; single wrap = neurilemma

• Many axons in CNS and PNS are unmyelinated
  • In PNS, Schwann cells hold small unmyelinated axons in
  surface grooves
  • Membrane folds once around each axon; does not spiral repeatedly
  around it
  • This wrap serves as the neurolemma
  • Basal lamina surrounds Schwann cell along with its axons

• continuous Conduction velocity factors

  • Diameter: larger ⇒ lower resistance ⇒ faster

  • Myelin: saltatory conduction greatly accelerates

  • Examples

  • Small unmyelinated: 0.5\text{–}2\,\text{m/s}

  • Small lightly myelinated: 3\text{–}15\,\text{m/s}

  • Large myelinated: up to 120\,\text{m/s}

unmyelinated axons

Nerve Regeneration (PNS)

• Possible if soma intact & some neurilemma present

• Requires Endoneurium for nerve fiber regeneration

• Steps

  1. Distal stump degenerates; macrophages clean debris (Wallerian degeneration)

  2. Soma swells; Nissl bodies disperse; nucleus off-center

  3. Axon sprouts multiple growth cones

  4. Schwann cells + basal lamina + endoneurium form regeneration tube → guide growth

  5. Axon reestablishes synapse; soma returns to normal; muscle fibers regrow

• Limitations: ≈ 1\text{–}2\,\text{mm/day}; may miswire; CNS axons lack neurilemma ⇒ poor regeneration

  • Damaged nerve fibers in the CNS cannot regenerate at all but suffers less trauma than the PNS being enclosed in bone

  • Regeneration in the PNS is facilitated by schwann cells, may be slow but not always perfect

Electrophysiology of Neurons

• Neural communication is based on electrical potentials and
  currents

• Electrical potential—difference in concentration of charged particles between one point and another. A form of potential energy that can produce current
  • Type of potential energy; measured in volts
  • Under some conditions, can produce a current

• Current—flow of charged particle from one point to another like ions

• Polarized: refers to a cell membrane across which there is a separation of electrical charge, so that one side is more positive and the other side is more negative

Resting Membrane Potential (RMP)

   Resting membrane potential (RMP)—charge difference across plasma membrane

• Typical neuron RMP: -70\,\text{mV} in an unstimulated, resting neuron (inside negative)

  • Negative value indicates more negatively charged particles on
    inside of membrane compared to outside

• Electrical currents in the body created by flow of ions+ + (Na , K , etc.)
  through gated channels in the membrane

• ions are unequally distributed between extracellular fluid
  (ECF) and intracellular fluid (ICF)

• Ionic contributors

  • [K^+]_{\text{ICF}} high; membrane highly permeable via leak channels ⇒ K+ efflux until equilibrium

  • [Na^+]_{\text{ECF}} high; limited permeability; small Na+ influx slightly offsets negativity

  • \text{Na}^+/\text{K}^+ ATPase: 3 Na+ out / 2 K+ in; maintains gradients & ≈ -3\,\text{mV} of RMP; consumes 70\% of neuronal ATP

  • Potassium (K+ ) has greatest influence on RMP due to the plasma membranes high permeability to K+
    •K+ is more concentrated in ICF compared to ECF
    • Cell membrane more permeable to K+ (through leak channels) than to other ions
    • As K+ leaks out, inside of membrane becomes more negative, creating slight local accumulation of the K+ on the outside of the membrane relative to the inside
    • Resulting electrical attraction brings K+ back in
    • Equilibrium is reached: no net movement of K+ occurs when
    tendency foe K+ to exit (down its concentration gradient) equals
    tendency for K+ to enter (by electrical attraction)

  • Sodium ( Na^{+} ) also influences the RMP but is much less permeable to Na+ than to K+

    • Na^{+} is 12x more concentrated in ECF compared to ICF, but membrane is much less permeable to Na^{+} than to K^{+}

    • Na^{+} diffuses into the cell, down its concentration gradient and attracted electrically, but it’s a relatively small amount

    • Cancels some of the negative charge, reducing the voltage across the membrane

      • Sodium-potassium(Na /K )+ + pump compensates for the continual leakage of Na+ and K+

      • • Moves Na+ out of the cell and brings K+ into the cell—
        maintains their concentration gradients
        • Contributes about -3 mV to the RMP
        • Works continuously and requires ATP
        • 70% of the energy requirement of the nervous system

ionic basis of resting membrane potential

Local (Graded) Potentials

Sensory neurons can be stimulated by chemicals, light, heat, or
mechanical forces

• Produced at dendrite/soma by stimuli (chemicals, light, heat, stretch)

• Features

• Opens Na+ channels, allows Na+ to enter

  • Entry of positively charged Na+ makes membrane potential less
    negative

  • Graded (proportional), decremental (fade with distance), reversible, excitatory (depolarize) or inhibitory (hyperpolarize)

  • Polarity is reduced, voltage is less negative—called
    depolarization

  • Depolarization: Na+ entry makes membrane less negative

    • spreads from the point of stimulation

    • Temporary, short-range change in voltage is a local potential

• Characteristics of local potentials

  • Graded—vary in magnitude with stimulus strength
    • Stronger stimuli open more Na+ channels, and they stay open longer

  • Decremental—get weaker the farther they spread from
    the point of stimulation

  • Reversible—if stimulation ceases, membrane voltage
    quickly returns to normal resting potential

  • Can be either excitatory or inhibitory

    • Depolarization is excitatory—makes a neuron more likely to fire an action potential)

    • Hyperpolarization (membrane more negative) is inhibitory—makes a neuron less likely to produce an action potential

excitation of a neuron by a chemical stimulus

Action Potentials (AP) rapid up-and-down change in voltage
produced by the coordinated opening and closing of voltage-
gated ion channels

• Only occurs where there is a high enough density of
  voltage-gated ion channels (trigger zone of axon)

• Depolarization: refered to the upward change in membrane potential during an action potential

• If excitatory local potential reaches trigger zone and is still strong enough, it opens enough voltage-gated Na +channels to generate an action potential

• All-or-none spike generated at trigger zone when local potential reaches threshold (≈ -55\,\text{mV})

• They do not decrease with distance (nondecremental), ensure consistent communication across long distances, they are unstoppable with irreversable nature

• Steps of an action potential:

  • Local potential spreads to axon hillock

  • Voltage at axon hillock must reach threshold—the
    minimum voltage to open voltage-gated channels (around
    −55 mV)

  • Voltage-gated Na+ channels open quickly

    • Voltage-gated K+ channels open more slowly

    • Na+ enters and depolarizes membrane further, quickly surpassing 0 mV

    • Na+ channels become inactivated, begin closing

  • Voltage peaks at +35 mV by the time Na+ inflow ceases

    • Membrane polarity has reversed—now more positive on the inside and negative on the outside

  • The voltage-gated K+ are fully open, K+ flows out of cell and
    membrane becomes more negative again— repolarization

  • K+ continues to exit and produces a negative overshoot
    hyperpolarization) 1 to 2 mV more negative than the original RMP

  • Membrane voltage returns to RMP as Na+ leaks into the cell
    

    

    The concentrations o Na+ and K+ on either side of the membrane do not change significantly during an action potential

• Movement of only a few ions can have a large effect on the
  membrane potential

  • Only about one in a million ions crosses the membrane during
    an action potential

  • Only the thin layer of ions close to the membrane is affected

• Even after thousands of action potentials, the cytosol still has a
  higher concentration of K+ and a lower concentration of Na+ than the ECF

• Characteristics of action potentials:

  • All-or-none law—if threshold reached, neuron fires up to
    maximum voltage; if threshold not reached, it does not fireV}

  • Non decremental—do not get weaker with distance

  • Irreversible—once started, an action potential travels all
    the way down the axon cannot be stopped

Refractory Periods

• Refractory period—period of resistance to stimulation; has
  two phases:

• Absolute refractory period: no new AP (caused by inactivation of voltage gated Na+ channels inactivated)

• Relative refractory period: an unusually stronger stimulus needed to trigger a new AP may fire (during hyperpolarization, larger depolarization or local potential is required to reach threshold)

  • no stimulus of any strength will trigger new action potential

  • occurs during depolarization and repolarization phases of action potential

  • refers only to a small patch of the membrane; other parts of the neuron can still be stimulated while a small area of it is refractory

Signal Conduction

   Unmyelinated axons and continuous conduction:

•     Unmyelinated axons have voltage-gated channels along
  their entire length

• Action potential at trigger zone causes Na+ to enter axon and diffuse into adjacent regions

• Depolarization opens voltage-gated channels

• Opening of voltage-gated ion channels results in a new action potential which then allows Na+ diffusion to excite membrane immediately distal to that

• Chain-reaction continues down axon:

  • Continuous (unmyelinated): sequential opening of channels along entire axolemma; relatively slow

  • Saltatory (myelinated): APs only at nodes; internodal Na+ diffusion renews spike at next node; fast & energy-efficient

continuous conduction of a nerve signal in an unmyelinated axon

•   Myelinated axons and saltatory conduction:

  • Action potentials can only be generated at the nodes,
    where voltage-gated ion channels are concentrated

  • Electrical signal must spread passively between nodes

    • Signal passes very quickly, but strength decreases (similar to a local potential)

  • When signal reaches the next node it is still strong enough
    to depolarize the membrane to threshold

    • Voltage gated Na+ channels open and a new, full strength action potential occurs

  • Action potential seems to “jump” from node to node

    • Moves faster through “insulated” segments covered with myelin

    • Slows down when it reaches the bare axon of the nodes

Synapses

point where an axon terminal meets the next cell (another neuron, gland cell, muscle cell)

• For neuron-to-neuron synapses:
  • Action potential arrives at end of axon of presynaptic neuron
  • Presynaptic neuron releases neurotransmitter
  • The postsynaptic neuron responds to it

• Electrical synapses: these are direct connections between neurons that allow ions and small molecules to pass through gap junctions, enabling rapid signal transmission without the need for neurotransmitter release.

• For chemical synapses: neurons communicate by neurotransmitters, also site of learning and memory, target of many prescription drugs, and site of action of drugs of addiction among other things

  • • Neurotransmitters diffuse across the synaptic cleft •

  • Bind to specific receptors on the postsynaptic membrane

  • Trigger a response in the postsynaptic neuron, which may be excitatory or inhibitory, influencing whether the action potential will propagate.

Basic Anatomy

• Presynaptic axon terminal: synaptic vesicles docked at active zones

• Synaptic cleft: gap between presynaptic neuron and
  postsynaptic neuron

  • ≈ 20\,\text{nm} gap with CAMs linking cells

  • Each neuron has cell-adhesion molecules (CAMs) reaching
    into the cleft

  • CAMs link the two neurons together

• Axon terminal of presynaptic neuron contains synaptic vesicles
  containing neurotransmitter

  • Many vesicles are docked on release sites on plasma
    membrane ready to release neurotransmitter

• Postsynaptic membrane: receptor & ion channel cluster (postsynaptic density) contains a postsynaptic density of neurotransmitter receptors and ion channels

  • Ligand-gated ion gates open when neurotransmitters bind to
    them

• Axodendritic, axosomatic, axoaxonic variants (last enables presynaptic modulation)

  • axodendritic: synapse where the axon of one neuron forms a connection with the dendrite of another neuron

  • axosomatic: synapse where the axon connects directly to the soma (cell body) of another neuron

  • axoaxonic: synapse where the axon of one neuron connects to the axon of another neuron, often playing a crucial role in presynaptic inhibition or facilitation.

  • These synaptic connections are essential for neural communication and influence overall neuronal activity.

  • dendrodendritic: a synapse where the dendrites of two neurons connect with each other, allowing for local communication and integration of signals between neighboring neurons.

  • axoaxonic: a type of synapse where the axon of one neuron forms a connection with the axon of another neuron, allowing for the modulation of neurotransmitter release and contributing to the regulation of synaptic strength.

• Neurotransmitter binding leads to ion flow, resulting in excitatory or inhibitory postsynaptic potentials, which influence the likelihood of an action potential in the postsynaptic neuron.

Neurotransmitter Categories (>100 known)

• Acetylcholine (ACh)—formed from acetic acid and choline

• Amino acids- triggering various physiological responses: glutamate, aspartate, glycine, \gamma-aminobutyric acid (GABA)

  • Glutamate: a major excitatory neurotransmitter in the central nervous system, playing a crucial role in synaptic plasticity and memory formation.

  • aspartate: spinal cord, effects similar to those of glutamate

  • glycine: inhibitory neurons of the brain, spinal cord, and retina: most common inhibitory neurotransmitter in spinal cord

  • GABA: a primary inhibitory neurotransmitter in the brain that helps regulate neuronal excitability and plays a vital role in reducing anxiety.

• Monoamines (biogenic amines)— synthesized from amino acids by removal of the –COOH group but retain the amino group

  • Catecholamines: epinephrine, norepinephrine (NE), dopamine

  • Others: serotonin, histamine

  • Norepinephrine: a neurotransmitter involved in arousal, attention, and the regulation of mood, which plays a key role in the body's fight-or-flight response. excites cardiac muscle, can excite or inhibit smooth muscle and glands depending on location

  • epinephrine: hypothalamus, thalamus, spinal cord, and adrenal medulola, effects similar to those of norepinephrine

  • dopamine: hypothalamus, limbic system, cerebral cortex, and retina, highly concentrated in substantia nigra of midbrain; involved in elevation of mood and control of skeletal muscles

  • serotonin: a neurotransmitter that stabilizes mood, feelings of well-being, and happiness; primarily found in the brain, intestines, and blood platelets, it plays a crucial role in regulating mood, appetite, sleep, and digestion.

  • histamine: a neurotransmitter involved in the regulation of sleep-wake cycles, attention, and arousal; primarily found in the brainstem and hypothalamus, it is also implicated in allergic responses and local immune reactions.

• Purines: ATP, adenosine

• Gases: nitric oxide (NO), carbon monoxide (CO); synthesized as needed rather than stored in vesicles

• Neuropeptides: chains of 2-40 amino acids;
  cholecystokinin (CCK) and endorphins, substance P, cholecystokinin, enkephalins, endorphins (dense-core vesicles)

  • Stored in large secretory granules (dense-core vesicles)

  • Some also function as hormones or neuromodulators

  • substance p: a neuropeptide involved in the transmission of pain and inflammation, often released from sensory neurons and plays a role in the body's pain perception.

  • Enkephalins: various areas of the brain, spinal cord, act as analgesics by inhibiting substance P, secretion increases during labor

  • \beta-endorphin: in digestive tract, spinal cord, and many parts of the brain; secreted as a hormone by the pituitary; suppresses pain; reduces fatigue; may produce "runner's high"

    

    
    

  • Cholecystokinin (CCK): a peptide hormone produced in the small intestine; stimulates gallbladder contraction, promotes satiety, and mediates the digestion of fats and proteins.

  • Nociceptin: a neuropeptide that plays a role in pain modulation and is involved in various physiological processes, including appetite regulation and stress response.

  • Neuromodulator: a type of neurotransmitter that modifies the activity of neurons and synapses, influencing mood, behavior, and cognitive function.

Representative Chemical Synapses

• not all neurotransmitters have an excitatory effect

• Are the site of learning and memory

• Excitatory cholinergic synapse-(ACh) acetylcholine is the
  neurotransmitter

  1. AP opens Ca^{2+} channels from depolarization of axon terminal

  2. Ca^{2+} enters, triggers vesicle exocytosis of ACh

  3. ACh diffuses across cleft, binds to postsynaptic receptors

  4. ACh receptors are ligand-gated Na+ channel open allow Na+ and K+ → EPSP membrane

  5. Entry of Na+ causes depolarizing postsynaptic potential

  

  An Inhibitory GABA-ergic synapse

• synapses that employ GABA as their neurotransmitter are called GABA-ergic synapses, which typically result in hyperpolarization of the postsynaptic membrane, making it less likely for an action potential to occur.

  • GABA opens ion Cl^- channels ⇒ hyperpolarization (IPSP less likely to fire action potential)

• GABA-ergic synapse—γ-aminobutyric acid (GABA) is
  the neurotransmitter

• postsynaptic receptor for the GABA neurotransmitter is a potassium channel

• Excitatory adrenergic (NE) Adrenergic synapse—norepinephrine (NE) is the neurotransmitter

  • G-protein coupled; activates cAMP second messenger → enzyme amplification, slower but powerful

  • Monoamines and neuropeptides bind to G-protein coupled
    receptors on postsynaptic membrane

  • Activate second-messenger systems such as cyclic AMP
    (cAMP)

  • Slower to respond than cholinergic and GABA-ergic synapses

  • Has advantage of enzyme amplification

adrenergic synapse:

• employs the neurotransmitter norepinephrine, facilitating the activation of specific receptors that lead to prolonged responses in target cells.

  • NE, other monoamines, and neuropeptides acts through second messengers such as cyclic AMP (cAMP)

  • the receptor is a transmembrane protein associated with G protein on the inner face of the membrane

  • 1. the unstimulated NE receptor is bound to a G protein

  • 2. binding of NE to the receptor causes the G protein to dissociate from it

  • 3. The G protein binds to adenylate cyclase and activates this enzyme, which converts ATP to cAMP

  • 4. cyclic AMP can induce several alternative effects in the cell

  • 5. one effect is to produce an internal chemical that binds to a ligant-gated ion channel from the inside, opening the channel and depolarizing the cell ATP is converted to cyclic AMP by adenylate cyclase

  • 6. Adenylate cyclase is activated, another is to activate preexisting cytoplasmic enzymes, which can lead to diverse metabolic changes (indusing a liver cell to break down glycogen and release glucose into the blood)

  • 7. yet another is for cAMP to induce genetic transcription, so that the cell produces new enzymes leading to diverse metabolic effects

GABA-ergic synapses, adrenergic synapses do have signal amplification

• a single NE molecule binding to a receptor can induce the formation of many cAMP’s. each of those can activate many enzyme molecules or induce the transcription of a gene to generate numerous mRNA molecules

• each can result in production of a vast number of enzyme molecules and metabolic products such as glucose molecules

• synaptic events require 0.5 ms or so with an interval called synaptic delay

  • the time from the arrival of a signal at the axon terminal of a presynaptic cell to the beginning of an action potential in the postsynaptic cell

Signal Termination (cessation of the signal)

• Stop transmitter release & clear cleft via:

  • Enzymatic degradation (e.g., AChE)

  • Reuptake (e.g., NE, amino acids) → MAO degrades in terminal

  • Diffusion away → astrocytes uptake in CNS

• Neurotransmitter degradation—enzyme in synaptic cleft breaks down neurotransmitter

  • Example: acetylcholinesterase (AChE) breaks ACh down into choline and acetate

• Reuptake—neurotransmitter or its breakdown products reabsorbed into axon terminal

  • Amino acids and monoamines also reabsorbed, degraded in axon terminal by enzyme monoamine oxidase (MAO)—target of some antidepressant drugs

• Diffusion—neurotransmitter or its breakdown products simply away from synapse into nearby ECF

  • astrocytes-

Neuromodulation

chemicals secreted by neurons that have long term effects on groups of neurons

• they adjust or modulate activity of neuron groups in various ways, increasing release of neurotransmitters by presynaptic neurons

• May alter the rate of neurotransmitter synthesis, release,
  reuptake, or breakdown
  • May adjust sensitivity of postsynaptic membrane

• Neuromodulators = long-term adjusters (frequency, synthesis, degradation, receptor sensitivity)

  • Nitric oxide (diffusible gas) is a simple neuromodulator

    • Gas that enters postsynaptic cells and activates second messenger pathways (for example, relaxing smooth muscle)

  • Neuropeptides chains of amino acids that can act as
    neuromodulators (endorphins/enkephalins) suppress pain pathways

    • Enkephalins and endorphins are neuropeptides that inhibit pain signals in the CNS

Neural Integration—the ability to process, store, and recall
information and use it to make decisions

• Chemical synapses allow for decision-making

• Brain cells are incredibly well connected, allowing for complex integration

  • Pyramidal cells of cerebral cortex have about 40,000 contacts with other neurons

• Trade off: chemical transmission involves a synaptic delay that makes information travel slower than it would if there was no synapse

Postsynaptic Potentials

Two types of postsynaptic potentials produced by
neurotransmitters:

• EPSP (excitatory postsynaptic potential): Depolarizing voltage
  change from the RMP toward threshold. ; usually results from Na+ flowing into cell

• IPSP inhibitory postsynaptic potential: hyperpolarizing;
  voltage becomes more negative than it is at rest

  • IPSP can result from K+ exit from cell or sodium Cl^{-} entry

  • Neurotransmitter effect depends on receptor subtype (e.g., ACh excitatory on skeletal muscle, inhibitory on cardiac muscle)

• Different neurotransmitters cause different types of postsynaptic potentials

  • Glutamate and aspartate produce EPSPs in brain cells

  • Glycine and GABA produce IPSPs

• A neurotransmitter might excite some cells and inhibit others,
  depending on the type of receptors in the postsynaptic membrane

  • Acetylcholine (ACh) and norepinephrine work this way

  • ACh excites skeletal muscle but inhibits cardiac muscle
    due to the expression of different types of ACh receptors
    on the different types of muscle cells

Summation & Modulation

Summation—the process of adding up postsynaptic
potentials and responding to their net effect

• Occurs in the trigger zone

• Some incoming nerve fibers may produce EPSPs while
  others produce IPSPs

• A neuron’s response depends on whether the net input is
  excitatory or inhibitory

• The balance between EPSPs and IPSPs enables the
  nervous system to make decisions

Two ways EPSPs can be added to reach threshold:

• Temporal summation: rapid EPSP succession at one synapse.

  a single synapse generates EPSPs so quickly that each is generated before the previous one fades

  

  Spatial summation: simultaneous EPSPs at multiple synapses add up to threshold at an axon hillock

  

  presynaptic Facilitation: one neuron (F) enhances another (S) via serotonin prolonging Ca^{2+} influx ⇒ ↑ NT release

• Presynaptic inhibition: is the opposite of facilitation neuron (I) releases GABA onto synaptic terminal ⇒ ↓ Ca^{2+} entry ⇒ ↓ NT release

• occurs when one presynaptic neuron suppresses another one

Neural Coding

• Qualitative info: “labeled-line” identity of active nerve (optic = light, etc.)

• Quantitative info (intensity):

  • Recruitment: more neurons (incl. high threshold) fire

  • Firing frequency: stronger stimulus ⇒ higher Hz

Neural Pools & Circuits

• Discharge vs facilitated zones (input neuron influence gradient)

• Circuit motifs

  • Diverging, converging, reverberating (oscillatory), parallel after-discharge (after-effect)

  • diverging: a circuit motif where one input neuron branches to activate multiple output neurons, allowing for widespread signal distribution.

  • converging: funnel where inputs are channeled into fewer outputs. A circuit motif in which multiple input neurons send signals to a single output neuron, enhancing the strength of the signal and allowing for integration of information from various sources.

  • reverberating: a circuit motif that involves feedback connections where the output signal re-excites the input neurons, creating a loop that can result in sustained activity and oscillatory patterns in neural signaling. Neurons stimulated each other in a linear sequence from an input to output neurons with some late in the path sending axon branches to neurons earlier in the path

  • parallel: a circuit motif that allows for simultaneous processing as multiple input neurons connect to multiple output neurons, facilitating an efficient and rapid response to stimuli by distributing signals across various pathways.

  • serial: a circuit motif where input signals are processed in a sequential manner, with each output neuron passing its signal to the next in line, often resulting in a more linear and straightforward pathway for signal transmission.

• Processing styles

  • Serial: one stream at a time (e.g., reading vs watching TV)

  • Parallel: simultaneous diverse pathways (e.g., driving integrates visual, auditory, proprioceptive cues)

Memory & Synaptic Plasticity

• Engram: anatomical memory trace; basis = plasticity of synapses

• Immediate memory: few s; reverberating circuits; enables “present moment” & sentence comprehension

• Short-term (working) memory: s → h; tetanic stimulation ⇒ Ca^{2+} buildup ⇒ synaptic facilitation; post-tetanic potentiation retrieves recent memories with minimal cue

• Long-term memory

  • Explicit (declarative): facts, events; conscious recall

  • Implicit (procedural & emotional): unconscious skills, habits, conditioned responses

  • Mechanisms: new dendritic spines, larger synapses, long-term potentiation (LTP) via NMDA receptors & Ca^{2+}-dependent signaling

• Forgetting: long-term depression (LTD); low frequency → low Ca^{2+} → phosphatases & proteasomes dismantle unused synapses

Degenerative & Demyelinating Disorders

• Multiple Sclerosis: CNS demyelination; autoimmune; onset 20–40 yr; neurological deficits ⇒ fatal 25–30 yr post-dx

• Tay–Sachs: GM2 ganglioside accumulation; Eastern-European Jewish infants; blindness, dementia; fatal < 4 yr

• Gliomas / Brain tumors: arise from mitotic glia; BBB limits chemo ⇒ surgery/radiation

• Alzheimer Disease

  • \beta-amyloid plaques, neurofibrillary tangles; cortex atrophy

  • ACh & NGF deficits; 11 % >65 affected; research seeks plaque clearance

• Parkinson Disease

  • Dopaminergic neuron degeneration (substantia nigra) ⇒ basal nuclei overactivity

  • Resting tremor, bradykinesia, pill-rolling; treated with L-dopa, MAO-B inhibitors, surgery

Conduction Velocity Examples (Numeric Recap)

• Small unmyelinated: 0.5\text{–}2.0\;\text{m/s}

• Small myelinated: 3\text{–}15\;\text{m/s}

• Large myelinated: \le 120\;\text{m/s}

Key Equations & Numeric Facts

• Resting membrane potential: V_{\text{rest}} \approx -70\,\text{mV}

• Threshold voltage: V_{\text{th}} \approx -55\,\text{mV}

• AP peak: +35\,\text{mV}

• Na\textsuperscript{+}/K\textsuperscript{+} pump: 3\,\text{Na}^+ \rightarrow \text{ECF},\; 2\,\text{K}^+ \leftarrow \text{ICF} + ATP hydrolysis

• Fast axonal transport: 200\text{–}400\,\text{mm/day}; Slow: 0.2\text{–}0.5\,\text{mm/day}

• Schwann cell myelin layers: up to \sim 100$$ wraps

End of comprehensive bullet-point notes for Chapter 12: Nervous Tissue.