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Functional distinctions in the nervous system

Somatic / autonomic nervous system: Somatic: Concerned with conscious, voluntary activity and perception (Skeletal muscle, sensory receptors and nerves) ...

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Functional distinctions in the nervous system

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  1. Functional distinctions in the nervous system • Central / peripheral nervous system: • Central: Brain and spinal cord • Peripheral: Nerves connecting the CNS with the rest of the body; ganglia (nodes) halfway between CNS and target organs, and plexus (braids) in the internal organs • Somatic / autonomic nervous system: • Somatic: Concerned with conscious, voluntary activity and perception (Skeletal muscle, sensory receptors and nerves). • Autonomic: Involuntary control of internal organs. Examples: Blood pressure, heart rate, sweat glands

  2. Schematic of a nerve cell Dendrites Terminal buttons Synapse Soma Axon Soma = body (greek) Dendron = tree Synapse = junction button = button (engl.)

  3. Neurons are controlled by excitatory and inhibitory afferent synapses

  4. neuromuscular (smooth muscle) Different anatomical types of synapses neuro-neural neuromuscular (skeletal muscle; ‘myoneural junction’)

  5. Muscle fibers and a branching nerve ending

  6. EM of a synapse

  7. Transmitter Nerve fiber (axon) Action potential Ca + + Receptor How a synapse works Voltage-sensitive channel

  8. + Ca++ in neurotransmitter exocytosis Action potential Synapsin CaM Ca++ Synapto- tagmin Kinase II P Synapto-brevin Ca++

  9. Synaptic transmission is an important target of drug action (1) Agonists (‘mimetic’ drugs) can augment or entirely substitute the effect of a neurotransmitter + + +

  10. Synaptic transmission is an important target of drug action (2) Antagonists (‘lytic’ drugs) can inhibit or entirely abrogate the effect of a neurotransmitter - - -

  11. Synaptic transmission is an important target of drug action (3) ‘Indirect mimetic’ drugs can promote the effect of the transmitter by interfering with its inactivation reuptake enzymatic inactivation

  12. Synaptic transmission is an important target of drug action (4) Presynaptic receptors form a feedback loop that can be selectively targeted by agonists and antagonists

  13. synthesis storage breakdown reuptake enzymatic inactivation Indirect agonists and antagonists may modify the availability of transmitter

  14. Types of synapses: Transmitters Acetylcholine Norepinephrine (Noradrenaline)

  15. More transmitters Glutamate Glycine Tyr-Gly-Gly-Phe-Met-Thr- Ser-Glu-Lys-Ser-Gln-Thr- Pro-Leu-Too-Muc-Hse-Xma- Kes-You-Sho-Rts-Igh-Ted- Val-Lys-Asn-Ala-His-Lys- Lys-Gly-Gln -Aminobutyrate (GABA) …and many more… -Endorphin

  16. Neurotransmitter receptors • Ligand – gated channels: • Nicotinic acetylcholine receptor • NMDA-type glutamate receptor • Glycine receptor • GABAA receptor • Serotonin receptor (5-HT3,) • G protein-coupled receptors: • Muscarinic acetylcholine receptor (several types) • ‘Metabolic’ glutamate receptors • Catecholamine receptors • 5-HT receptors other than 5-HT3 • GABAB receptors • Peptide receptors

  17. Parasympathetic Sympathetic Somatic M Medulla oblongata Heart Smooth muscle in gut and blood vessels Ganglia N ,  M N M Glands D1 Kidney arteries Spinal cord N N Adrenal gland Skeletal muscle N

  18. Why target the autonomic nervous system? It controls Hypertension, cardiovascular disease • Heart rate • Blood pressure • Blood flow distribution • Motility of the digestive tract • Bronchial contraction / dilatation and secretion • Body temperature; sweating Surgical patients Surgical patients Asthma / bronchitis Synapses in the autonomic nervous system as drug targets

  19. ‘Mydriasis’ = wide pupils Sympathetic stimulation Parasympathetic stimulation ‘Miosis’ = narrow pupils

  20. ‘Mydriasis’ = wide pupils Sympathetic stimulation (cocaine, ‘speed’) Parasympathetic stimulation • -opiod receptors (heroin) ‘pinpoint pupils’

  21. Somatic NS Autonomic NS Endocrine system Somatic NS Autonomic NS Endocrine system The nervous and the endocrine system are not cleanly separated Noradrenaline Acetylcholine

  22. neuromuscular (smooth muscle) Different anatomical types of synapses neuro-neural neuromuscular (skeletal muscle; ‘myoneural junction’)

  23. Portal vessels may direct hormones to specific tissues CRH, … Neurons in the hypothalamus anterior lobe: ACTH, … Hypophyseal gland posterior lobe: oxytocin, vasopressin

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