A&P 1: Nervous System Tissue Physiology

Myelin sheath

Insulating covering around axon consisting of repeating concentric glial cell plasma membrane layers composed of lipids and proteins

Myelination

Neurolemmocyte or oligodendrocyte encircles axon

PNS: plsama membrane wraps in layers with cytoplasm/nucleus squeezed to periphery (neurilemma) in PNS; many neurolemmocytes typically needed (hundreds/thousands)

CNS: cytoplasmic extensions wrap until repeatedly; one oligodendrocyte can wrap several axons

Neurofibril node

Node of Ranvier; gap between neurolemmocytes or adjacent oligodendrocyte wraps

Wallerian degeneration

Macrophages remove debris through phagocytosis to break down severed axon portion and its myelin sheath

Axon regeneration

PNS nerve repair system for axon trauma (cut, crush, etc..); limited in CNS due to lack of nerve growth factor, secretion of growth-inhibitory molecules, crowding, scar formation

Depends on amount of damage and distance between damage site and innervated structure (> = less chance of repair)

Proximal portion seals ob by membrane fusion & swells due to axoplasmic flow

Neurilemma and remaining endoneurium form regeneration tube

Axon regenerated and remyelinated

Innervation restored when contact reestablished

Leak channel

Allows passive diffusion of specific ions

Na+/K+ channels located throughout neuron plasma membrane; role in RMP

Chemically gated channel

Channel that temporarily opens in response to neurotransmitter binding allowing specific ion to diffuse

Voltage-gated channel

Channel that temporarily opens in response to changes in electrical charge (potential) across plasma membrane allowing specific type of ion to diffuse

Typically one gate, but Na+ channels have two

Na+ voltage-gated channel

Triple gate channel allowing passage of Na+ in response to MP change

Resting state: inactivation gate open, activation closed; no entry

Activation state: activation and inactivation gates open in response to voltage change; Na+ moves in

Inactivation state: activation gate open, inactivation briefly closed following Na+ and cannot be reopened, preventing Na+ entry

Resting state reestablished with activation gate closing, inactivation gate opening; triggered by repolarization

Modality-gated channel

Channel on dendritic ending that opens/closes in response to specific sensory stimulus (temp, pressure, light)

Voltage (V)

Measures amount of different in electrical charge between two areas; represents potential energy

V or mV

Current (I)

Movement of charged particles across barrier that separates charge difference; greater movement = greater charge (intensity); electrical energy that can be used for work

Resistance (R)

Opposition to movement of charged particles; barrier between charged areas

Measured in Ohm’s

high R = low V

Ohm’s law

Current = Voltage/Resistance

Difference in charge on either side of membrane (voltage) due to concentration differences

Membrane resists due to phospholipid bilayer

Ion channels change resistance; diffusion generates current

Neuron at rest

Neuron state with cytosol has concentration gradients for K+, Na+, Cl- across entire neuron

More K+ inside than outside in initial and conductive segments, and voltage-gated Ca2+ channels in transmissive segment establishing RMP

Resting membrane potential

Electrical charge difference resulting from K+ and Na+ ion movement (chiefly though leak channels) as well as other ions (phosphate, organic molecules)

Established by K+ diffusing out of cell (chemical gradient) leaving larger more negative molecules inside cell (phosphate, proteins)

K+ movement opposed by electrical gradient; movement reaches equilibrium when gradients forces are equal (-90mV)

Na+ moves into neuron through lead channels down chemical and electrical gradient; limited channels reduce impact (~+23mV)

Na+/K+ pumps contribute ~3mV moving Na+ out more than K+ in; maintain concentration gradient

Graded potentials

Small (<1mV) short-lived changes in RMP

Established in neuron receptive segment when chemically gated channels open (cation, K+, Cl-) in response to neurotransmitter binding

Ions move along membrane in local current (like charges repel) which dies out quickly after closure due to resistance from cytosol

Vary in degree (“graded”) and direction of change (+/-) of RMP based on magnitude of stimulus (degree) and type of channels (cation net + = depolarization, cl/k = hyperpolarization)

Postsynaptic potential

Graded potential in postsynaptic neuron established in receptive segment

Can be excitatory/ESPS (+, depolarized) or inhibitory/ISPS (-, hyperpolarized)

Numerous potentials can occur simultaneously because many neurotransmitters can bind at once; outcome determined by initial segment

1) Neurotransmitter released, binds to receptor

2) channels open (cation > Na+ = EPSP, K+ or Cl- = IPSP)

3) PSP established, temporarily E/I state

4) local current becomes weaker at it moves toward initial segment

Summation

Changes in membrane potential established in receptive segment move to initial segment (axon hillock) and are summed

Spacial and/or temporal

Threshold membrane potential

Minimum voltage change in MP determining whether action potential is initiated;

RMP +15mV (~ -55mV) triggers voltage-gated channels; all-or-none rule applies (same intensity AP regardless of amount past threshold, no AP for subthreshold)

Requires multiple ESPS, can be inhibited by too many ISPS

Spatial summation

Multiple presynaptic neurons release neurotransmitters at various locations onto receptive segment

Generates ESPS, ISPS, or both

Temporal summation

Single presynaptic neuron repeatedly releases neurotransmitter producing multiple ESPS or ISPS at same location in very short duration; ESPS or ISPS

Depolarization

Gain in positive charge within neuron changing RMP from negative to positive

Reversal in polarity due to voltage-gated channels moving Na+ in

1) Threshold of -55mV reached when Na+ flows within cytosol region from adjacent areas triggering Na+ channels

2) Depolarization to +30mV when Na+ rapidly enters changing RMP; inactivation gates close, temporarily preventing reopening

1-2 repeat in adjacent areas downstream propagating AP away from cell body toward synaptic knob

Repolarization

Return to negative RMP from positive due to voltage-gated channels moving K+ out

3) Repolarization to -70mV after threshold triggers K+ channels at -55mV (slower than Na+, fully open after depolarization ends); gates remain open until sufficient K+ exit to change RMP to baseline

4) Hyperpolarization to -80mV when K+ channels remain open longer than needed

5) -70mV RMP reestablished by leak channels and Na+/K+ pumps after voltage-gated channels close

3-5 repeat in adjacent downstream regions propagating repolarization along axon to synaptic knob

Nerve impulse

Nerve signal; propagation of action potential (Na+ channel then K+ channel)

Refactory period

Brief period after AP initiation of axon downtime

Absolute: ~1ms before onset no amount of stimulus can initiate second potential thereby allowing unidirectional AP movement; depolarization and most of repolarization when VG Na+ channels change to inactivated state ensuring

Relative: hyperpolarization following ARP; another AP can be initiated by requires more stimulus

Local anesthetic

Lidocaine or other numbing agents block nerve signal; even ice can slow AP propagation

Continuous conduction

Process in unmyelinated axons involving sequential opening of VG Na+ & K+ channels along entire length of axon

Saltatory conduction

Process in myelinated axons where APs occur only in neurofibril nodes; “jump” from node to node

AP occurs at node

Na+ diffusion (no AP) myelinated region through axoplasm (fast, slowing with resistance as distance increases)

New AP occurs at next node when current arrives in axoplasm opening VG channels

Repeats down axon until synaptic knob reached

Faster than continuous conduction (120 m/s vs 2 m/s)because AP occurs only at nodes and not entire length; also requiries less energy by Na+k+ pumps to maintain RMP

Transmission

Occurs when neurotransmitters are released from synaptic knob

1) Nerve impulse reaches synaptic knob

2) VG Ca2+ channels open with depolarization moving Ca2+ into SK

3) Neurotransmitter released when Ca2+ binds to vesicle proteins triggering exocytosis (~300/signal); prior to AP Ca2+ pumps establish and maintain concentration gradient

4) Neurotransmitter attaches to ligand receptors of effector (muscle, gland) or other neuron after diffusing through cleft

Neurons can contain multiple neurotransmitters but vesicles contain only one type each

Neurotoxicity

Damage to nervous tissue from toxic substances produced in body (e.g. beta amyloid, oxygen free radicals), from microbes (e.g. botulinum toxin, tetanus toxin), synthetic substances (e.g. pesticides, industrial solvents, ethanol, chemical medications (chemotherapy, radiotherapy, organ transplant)

Causes AP propagation interference, alteration of synapse event, structure change harming or killing cell

Velocity

Speed of AP; dependent on axon diameter (larger = faster) and myelination (myelinated = faster)

Nerve fibers grouped based on velocity

A: 150 m/s;

B: 15 m/s

C: 1 m/s

Most somatic sensory neurons, somatic motor neurons are A. B & C for visceral sensory, autonomic motor neurons and small somatic sensory neurons in skin

Frequency

Rate of voltage (amplitude) remains the same # of APs in period can vary. Intense stimulus generates more signals, which brain interprets as more intense

Higher rate can also influence type of neurotransmitter released

Neurotransmitter

small, organic molecule synthesized by neurons, store in SK vesicle, released by exocytosis following Ca2+ entry and binding to target cell receptor to trigger response

~100 known molecules; some do not meet all criteria

Can be excitatory (induce ESPS) or inhibitory (induce ISPS), sometimes both depeding on specific response caused in target

Can be direct (recptor opens channel) or indirect (second messenger triggers effects)

May be removed from SK by digestion (e.g. acyetylcholinesterase), reuptake & digestion (e.g. MAO), diffusion & uptake by glial cells which may be influenced by medication (SSRI)

Acetycholine (ACh)

Differs structurally from other neurotransmitters

Primary neurotransmitter at neuromuscular junction and used by autonomic nervous system

Synthesized from acetate and choline and digested by acetylcholinesterase enzyme in cleft for choline reabsorption in knob

Effect depends on target cell with direct effect on nicotinic/ionitropic receptor (ESPS) and indirect in muscarinic/metabolic receptors (G protein pathway > ESPS or ISPS depending on receptor type)

Biogenic amines

Monoamines; derived from amino acids by removal of carboxyl (-COOH) and addition of other functional group by enzymes in cytosol with retention of single amine group

Catecholamine

Biogenic amine synthesized from tyrosine; contain catechol group

Dopamine, norepinepherine, epinepherine

Indolamine

Biogenic amine containing indole group

Synthesized from histidine (histamine) or tryptophan (serotonin)

Amino acids

Protein monomers; glutamate, aspartate, serine, glycine, gamma aminobutyric acid (GABA, modified amino acid)

Neuropeptides

Chains of 2-40 amino acids such as opiates (e.g. enkephalins, beta-endorphins), substance P

Neuromodulators

Substances that locally regulate or alter response of neurons to neurotransmitters by facilitating (more release, slower breakdown, slower reuptake, or more receptors) or inhibiting (less release, faster breakdown, faster reuptake, less receptors)

Nitric oxide

Short-lived small, nonpolar gas synthesized from arginine that is produced and released by postganglionic neurons on as needed basis

Involved in learning and memory; relaxation of muscle in the digestive tract; relaxation of smooth muscle in blood vessels

Classified as neurotransmitter or neuromodulator as it is not stored in vesicle and enters cells in all directors, providing retrograde meas of communication

Endocannabinoids

Small, nonpolar molecules produced and released on demand from postsynapic neurons

Binding in presynaptic neuron decreases neurotransmitter release, altering learning memory, appetite, and suppressing nausea

Most prevalent receptors in the brain

Dopamine

Produces inhibitory activity in the brain; important roles in cognition (learning, memory), motivation, behavior, and mood; decreased levels in Parkinson disease; amphetamines increase release; cocaine decreases removal from synaptic cleft; ecstasy increases release

Type of catecholamine

Norepinephrine

Noradrenaline; neurotransmitter of sympathetic PNS and various regions of the CNS; amphetamines increase release; cocaine decreases removal from synaptic cleft; ecstasy increases release

Type of catecholamine

Epinephrine

Adrenaline; neurotransmitter with various effects in thalamus, hypothalamus, and spinal cord

Type of catecholamine

Histamine

CNS neurotransmitter with role in sleep and memory

Type of indolamine

Serotonin

Involved in sleep, appetite, cognition (learning, memory), and mood; fluoxetine (Prozac) decreases reuptake; ecstasy increases the release; LSD binds to most receptors

Type of indolamine

Glutamate

Excites NS to promote cognitive function (learning and memory); most common neurotransmitter in the brain; stroke causes excessive release, resulting in neuron death

Aspartate

Amino acid which primarily excites in descending motor pathways of spinal cord to skeletal muscle

Serine

Amino acid which activates diverse areas in the brain

GABBA

Modified amino acid synthesized from glutamate

Primary inhibitory neurotransmitter in the brain; also influences muscle tone; alcohol, diazepam (Valium), and barbiturates increase inhibitory effects

Enkaphalin

Natural opioid; helps regulate noxious/painful stimuli response

Beta-endorphin

Prevents release of pain signals from neurons and fosters a feeling of well-being; morphine mimics endorphins; heroin is converted to morphine in the body

Neuropeptide Y

Involved in memory regulation and energy balance (increased food intake and decreased physical activity)

Somatosin

Inhibits activities of neurons in specific brain areas

Substance P

Assists with pain information transmission into the brain

Cholecystokinin

Helps mediate satiation (fullness) and repress hunger by stimulating neurons in brain

Neurotensin

Helps control and moderate the effects of dopamine

Adenosine

Part of a nucleotide with inhibitory effect on neurons in brain/spinal cord

Neuronal pools

Neuronal circuits/pathways; complex patterns of neuronal activity

Converging circuit

Inputs come together at single postsynaptic neuron

E.g. sensory neurons synapse in salivary nucleus of brainstem (see food/cues, smell food, hear food prep)

Diverging circuit

Info spreads from one presynaptic neuron to several postsynaptic neurons

E.g. cerebellum motor cortex engaging thousands of muscle fibers

Reverberating circuit

Feedback produces repeated cyclical stimulation (reverberation); may continue until inhibitory stimuli or synaptic fatigue breaks cycle

E.g. breathing during sleep

Parallel-after-discharge-circuit

Simultaneous input transmission along several neuron pathways to common postsynaptic cell

Can vary in number of neurons in pathway (more > longer transmission time) and input arrives at varying times

Involved in higher order thinking (math)