3a and b Physiology OF THE Nervous System PDF

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PHYSIOLOGY OF THE NERVOUS SYSTEMComplex organisms require integrated nervous system (and endocrine system)[integrated through the hypothalamus]Specialization: specific cells perform specific functions1. Sensory or afferent cell (afferent nerves) conduct stimuli from surface tocentral position of org...

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Physiology 3a and b

PHYSIOLOGY OF THE NERVOUS SYSTEM Complex organisms require integrated nervous system (and endocrine system) [integrated through the hypothalamus]

Specialization: specific cells perform specific functions 1. Sensory or afferent cell (afferent nerves) conduct stimuli from surface to central position of organism 2. Contact motor neuron (efferent nerves) relays impulse to effector cells (eg. muscles/glands) 3. Integration is required eg. Central nervous system based on interneurons interposed between afferent and efferent neurons (integration of endocrine system)

Classification of nervous system Classification of the NS is arbitrary according to: 1. Topographical / physiological grouping of nerve 2. Cells or nervous processes

Main cell types in NS: 1. neurons are structural & functional units

2. neuroglia are support tissue

Terminology pertaining to the Nervous system (NS) 1. 2. 3. 4. 5.

A group of nervous cells in the brain and spinal cord is a centre or nucleus A group of nervous cells in the peripheral nervous system is a ganglion A fibre that carries information toward a synapse is a presynaptic fibre A fibre that carries information away from a synapse is a postsynaptic fibres With regard to ganglia (in the PNS) reference is made to pre- and postganglionic fibres. 6. Afferent fibres vs. efferent fibres: a. Afferent fibres or sensory fibres because they are responsible for the perception of sensation. b. Efferent fibres or motor fibres because they control muscle contraction. 7. A group of fibres in the peripheral nervous system that are responsible for similar organs and functions is a nerve and those in the CNS are referred to as a tract. 8. A nerve can have an afferent, an efferent or both components, where the latter is a mixed nerve. a. Afferent fibres = ascending tracts b. Efferent fibres = descending tracts

Physiology 3a and b 9. NS consists of left and right halves that are relatively symmetrical. 10. Peripheral, Autonomic (Sympathetic & parasympathetic) and Enteric nervous systems (in GIT) 11. Many nerve fibres cross the midline in the brain and spinal cord, which ensures functional harmony between halves. 12. NS - connective tissue membranes a. pia mater (inner) b. arachnoid mater (middle) c. dura mater (outer)

Conduction of nerve impulse Nerve conduction is possible due to the following vital aspects e.g. I. II. III. IV. V. VI. VII.

Plasma membrane characteristics Differences in membrane potential Maintenance of membrane potential (maintained actively through ATPase) Action potential Refractory period Transmission of nerve impulse Transmitter substances (regulating factor; specifically at synapses)

Prerequisites making nerve impulses possible: I. Plasma membrane characteristics a. Permeability of the membrane for K+ ([K+] in cell is 20 to 50 fold greater compared to outside cell) (much higher in ICF compared to ECF; electrical gradient maintained) b. Inability of macromolecules (proteins, anions) to diffuse through the membrane (contributes to electrical difference; colloid pressure due to these inside) c. High [Cl] outside cell slowly moves through membrane d. Permeability of membrane to Na+ (1/20th of that of K+ in cell)

Physiology 3a and b II. Differences in membrane potential (creates electrical difference) a. K+ tends to move out of cell based on concentration gradient when membrane becomes more permeable b. Excess anions that remain in cell cause negative charge in cell, which limits further out-flux of K+ c. Cl- moves slowly into cell with concentration gradient and neutralizes electrical effect of Na+

III. Maintenance of membrane potential a. (-70mV) (actively maintained by Na-K ATPase pump; K into cell and Na out of the cell creating an imbalance b. Na+K+ATPase pump actively maintains membrane potential c. ATPase pump actively “pumps” Na+ out and K+ into cell

IV. Action potential a) Includes the following events: I. II. III. IV. V. VI. VII.

Nerve stimulation Impulse > threshold value (then impulse will be conducted) Local depolarisation Membrane permeability increases to Na+ (diffuse in, K diffuses out) Transmembrane potential (Pm) is reduced (inside of membrane becomes relatively less negative); PNa+ > PK+ Permeability to Na+ increases and Na+ moves across membrane into cell Membrane potential (Pm) is restored by out-flux of K+ and inhibition of further Na+ influx

Refractory period

Physiology 3a and b V. Refractory period (recovery period) a. Membrane is in depolarised state (no electrochemical difference across membrane) b. Active Na+K+ATPase pump required to restore initial membrane potential c. Involves active “pumping” of Na+ out and K+ into cell

VI. Transmission of nerve impulse a. b. c. d.

Connections between nerve terminal and next cell = synapse Synaptic cleft = 500A (20 micrometre) Release of transmitter substance Transportation across synaptic cleft

VII. Transmitter substances a. E.g. neuromuscular transmission = Acetylcholine (Ach) (most common in muscular system) b. Ach released from presynaptic membrane c. Ach transported across synaptic cleft d. Ach binds to postsynaptic membrane e. Depolarisation of postsynaptic membrane f. Increased permeability of postsynaptic membrane g. = Typical “Cholinergic synaptic stimulation h. Ach hydrolysed by acetylcholine esterase

Physiology of the Nerve impulse (from Frandson et al textbook) • •

Nerves rapidly transmit information from one body site to another via nerve impulses (i.e. action potential propagated along the axons of neurons within the nerves) The resting membrane potential of neurons depends mainly on nongated potassium channels in the cell membrane and the electrogenic Na-K-ATPase / Na-K pump

Physiology 3a and b •

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Continuous exit of potassium from the cell down its concentration gradient and the continuous activity of the pump maintain a difference in charge across the membrane so that the interior is negative relative to the exterior (i.e. resting membrane potential) Axonal cell membranes of neurons contain voltage gated Na channels These channels are closed at normal resting membrane potentials but rapidly open when the membrane potential is brought to threshold value This results in the inward movement of Na+ (down its concentration gradient) and a large, rapid membrane depolarization At the peak of the action potential (maximal depolarization), the sodium channe;s close and some additional voltage-gated potassium channels are open The closing of the Na+ channels and the exit of additional K+ repolarizes the membrane The exit of additional K+ produces a small afterhyperpolarization until resting conditions can be reestablished When an action potential occurs on the axon of a neuron, the membrane potential of adjacent areas is altered by local movement of charge Normally this causes the Na+ channel adjacent area to reach their threshold voltage and another action potential is elicited By this means, action potentials can be propagated along axons Propagation normally occurs in only one direction, in part because the Na+ channels where the action potential just occurred are refractory to another stimulus This refractory period is a characteristic of normal Na+ channels and the channels rapidly pass through this period so that they are no longer refractory when another impulse arrives

Synapses a. In invertebrates : electrical synapses where membranes are in direct contact → Electrical synapses are essentially gap junctions between the cell membranes of adjacent neurons that permit ionic exchange. b. In vertebrates: chemical synapses where neurotransmitters act as transmitter molecules, although smooth and cardiac muscle are characterised by electrically connected gap junctions → Biological control mechanism → Not in direct contact → Synaptic cleft present

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Synapses are specialized junctions where information is exchanged between neurons or between a neuron and the cell or cells that it innervates

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Information exchange at chemical synapses entails the release of a chemical neurotransmitter from the presynaptic neuron When an action potential arrives at the terminal end of the presynaptic neuron, the change in membrane potential is believed to be responsible for opening voltage-gated calcium channels.

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The calcium concentration within the cytosol is lower than the calcium concentration in the extracellular fluid, so calcium can diffuse through the open channels into the cell down its concentration gradient. The increase in intracellular calcium within the terminal end of the presynaptic neuron is associated with exocytosis of neurotransmitters stored in secretory vesicles within the presynaptic neuron. Typically, an individual neuron contains vesicles with only one primary neurotransmitter, but a wide variety of substances have been found to function as neurotransmitters. The cell membranes of presynaptic and postsynaptic neurons (or other target cells) are not in immediate contact. A small but distinct separation exists, and the space between is the synaptic cleft. Neurotransmitters released by the presynaptic neuron must diffuse across the synaptic cleft to have their effect on postsynaptic neurons, or target cells. However, this diffusion occurs almost instantaneously because of the very small size of the cleft (average 20 nm, or about a millionth of an inch) Neurotransmitters typically bind to cell membrane receptors on postsynaptic neurons or target organs. At synapses between neurons, the binding changes the postsynaptic membrane’s permeability to ions (either directly or indirectly via second messengers), and this in turn produces a change in the membrane potential of the postsynaptic neuron. Synapses and the neurotransmitters that depolarize the postsynaptic neuron are excitatory synapses and excitatory neurotransmitters Synapses and neurotransmitters that hyperpolarize the postsynaptic neuron are inhibitory. The change in postsynaptic membrane potential produced by excitatory neurotransmitters is an excitatory postsynaptic potential (EPSP), while an inhibitory neurotransmitter produces an inhibitory postsynaptic potentials (IPSP). Typically, excitatory neurotransmitters cause membrane depolarization by increasing the membrane’s permeability to sodium While inhibitory neurotransmitters increase the membrane’s permeability to either potassium or chlorine. Hyperpolarization of the cell membrane can be brought about by either an increased rate of potassium exit from a cell or an increased rate of chlorine entry into the cell down their respective concentration gradients. The amount of excitatory neurotransmitter released by a single action potential in a single presynaptic neuron is constant. However, it is also typically insufficient to depolarize the postsynaptic neuron to a threshold voltage at which an action potential can be elicited. Therefore, to reach threshold voltage in a postsynaptic neuron, the change in voltage produced by multiple EPSPs must be summated. Summation of EPSPs is classified as either temporal or spatial. Temporal summation occurs when a single presynaptic neuron releases neurotransmitter repeatedly before the effect of each single release is lost. When effective summation occurs, the additive effects of the multiple releases are enough to produce an action potential in the postsynaptic neuron. Spatial summation occurs when simultaneous or nearly simultaneous neurotransmitter release occurs at more than one synapse on the postsynaptic neuron. Spatial summation is possible because neuron cell bodies typically have multiple junctions with many presynaptic neurons.

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After a neurotransmitter has been released and had its desired effect on the postsynaptic neuron, it must be removed to prevent continuous stimulation of the postsynaptic neuron. The specific mechanisms by which neurotransmitters are removed from neural synapses vary among neurotransmitters. However, in general these can be any one or a combination of the following: 1. enzymes in the area of the synapse degrade the neurotransmitter; 2. cell membrane transport systems absorb the neurotransmitter; or 3. the neurotransmitter diffuses away from the area of the synapse. Typically, as described earlier, a single neuron and its dendrites contain multiple synaptic junctions and receive synaptic input from multiple presynaptic neurons, so a single neuron may receive impulses from several sources. This pattern or organization is described as convergence Divergence is the opposite: each axon branches so that synaptic connections are made with many neurons). These organizational patterns permit information to be widely distributed throughout a neural network (divergence) or permit multiple sources of information to be brought to focus on a single neuron for a focused response (convergence). For example, a single neuron can be simultaneously stimulated by excitatory and inhibitory neurotransmitters from different presynaptic neurons (a converging network). The property of spatial summation permits the neuron receiving these converging inputs to integrate the different stimuli and respond appropriately.

Types of synapses: 1.Neuromuscular synapses (nerve + muscle) 2.Synapses between neurons 3.Excitatory synapses 4.Inhibitory synapses

1. Neuromuscular synapses •

Nerve terminals of a motor neuron form synapse with skeletal muscle

2. Synapses between neurons • • • •

Similar to neuromuscular synapses, but these neurons receive synaptic input from many other neurons, Signal transmission may be either excitatory synapses or inhibitory synapses, Impulse does not necessarily cause impulse in target cell, Many other neurotransmitters are involved.

Physiology 3a and b 3. Excitatory synapses: • • •

Cause excitatory post-synaptic potential (EPSP) Na, K, Cl involved similar to neuromuscular synapse Interior of cell becomes less negative

4. Inhibitory synapses: • •

Cause inhibitory post-synaptic potential (IPSP) Only Cl involved: Outward flow of K+ and inward flow of Cl- so that interior of cell becomes more negative.

Neurotransmitters 1. Small molecule transmitters → → → →

Amino acids Biogenic amines Acetyl choline ATP

Note: All small molecule neurotransmitters are important in the central nervous system, while Ach & norepinephrine dominate in the peripheral nervous system

2. Agonists and antagonists

3. Neuropeptides → Endorphins & encephalin → Multipurpose neuropeptides → Nitric oxide

Small molecule transmitters a) Amino acids i). Glutamate = excitatory neurotransmitter in CNS ii.) GABA = most common inhibiting neurotransmitter (gamma-aminobutyric acid)

b) Biogenic amines i.) Biogenic amines synthesised from the amino acid tyrosine: → Dopamine → Epinephrine (adrenaline) / norepinephrine (noradrenaline) = catecholamine's ii.) Biogenic amine synthesised from tryptophan = serotonin iii.) Biogenic amine synthesised from histidine = histamine (stimulates inflammation)

Physiology 3a and b Agonists and antagonists 1. Agonist binds and activates receptor in similar way as transmitter 2. Antagonist binds receptors so that fewer receptors are available – inhibits response

Neuropeptides (ca. 100 identified and consist of up to 40 amino acid molecules) 1. Endorphins & encephalin Reduce pain sensation (e.g. myocardium) or induce state of euphoria – related to opioids like morphine & heroin

2. “Multi-purpose” neuropeptides = these are released as both neuropeptides from nerve terminals and hormones from endocrine glands e.g.. TRH, CCK, Oxytocin, LHRH, VIP, Vasopressin

3. Nitric oxide (NO): NO is produced by Ca2+−dependant activation with nitric oxide synthase (NOS) NO is highly active and the signal pathways are in all directions – (vasodilation of smooth muscle)

Neurotransmitters (from Frandson et al textbook) • •

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Most neurotransmitters can be classified as amino acids, monamines (modified amino acids) or polypeptides While more than 20 compounds have been proved to function as neurotransmitters (and the list will surely grow), some are especially prevalent throughout the nervous system and should receive individual consideration. Acetylcholine (derived from the amino acid choline) is the neurotransmitter released at the neuromuscular junction on skeletal muscle by some peripheral neurons of the autonomic nervous system (ANS) and found at many synapses throughout the central nervous system (CNS). Neurons releasing acetylcholine are classified as cholinergic, and this term is also applied to synapses for which acetylcholine is the neurotransmitter. Two general classes of acetylcholine (also termed cholinergic) receptors, nicotinic and muscarinic, are found at cholinergic synapses. The enzyme acetylcholinesterase is responsible for rapidly degrading acetylcholine and thus terminating its action at cholinergic synapses.

Norepinephrine is the neurotransmitter used by most peripheral neurons in the sympathetic division of the ANS and at synapses at several sites in the CNS. Presynaptic neurons and synapses using norepinephrine are termed adrenergic, and this term is also applied to cell membrane receptors that bind norepinephrine.

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The term adrenergic has been applied to these receptors because epinephrine, or adrenaline, also binds to these receptors. (Adrenaline is the British term for epinephrine, which is released from the adrenal gland.) Adrenergic receptors may be classified as α1, α2, β1, or β2 according to their relative binding affinities for various adrenergic agonists. Epinephrine and norepinephrine are both classified as catecholamines because of their chemical structure and because they are derived from the amino acid tyrosine. Dopamine is another catecholamine that functions as a neurotransmitter within the central and peripheral nervous systems, and specific dopamine receptors also exist.

γ-Aminobutyric acid (GABA) is the most prevalent inhibitory amino acid neurotransmitter in the CNS. Binding of GABA to its receptor produces neuronal hyperpolarization (inhibition). Several agents that act as sedatives, tranquilizers, and general muscle relaxants have part of their effect via promoting GABA’s effects on the CNS. These include alcohol, barbiturates, and the benzodiazepines (e.g., diazepam and chlordiazepoxide). Some of these agents bind directly to GABA receptors; others seem to facilitate the action of endogenous GABA. The GABA receptors may also be the principal target for some general anaesthetics.

Glutamate is the predominant excitatory neurotransmitter in the CNS, and several subtypes of glutamate receptors have been identified. One subtype of glutamate receptor, the NMDA receptor (named for the agonist Nmethyl-D-aspartate), are found in high concentrations in areas within the brain that are involved with memory and learning. Stimulation of NMDA receptors is believed to bring about long-term potentiation of transmission in neural pathways in these areas.

Physiology 3a and b

SENSORY PERCEPTION 1. Sensory receptors 1. Peripheral nervous system contains 2 functional units: a. afferent and b. efferent divisions 2. Sensory receptors monitor internal and external environment and conduct information via efferent fibres to the central nervous system. 3. Efferent division of the peripheral nervous system conn...