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NEUROTRANSMITTERS

NEUROTRANSMITTERS. Classic Characteristics:. Synthesized in the neuron. Become localized in presynaptic terminal. Bind to receptor site on postsynaptic membrane. Removed by a specific mechanism from its specific site of action. Classification. Small molecule transmitters: Amino acids:

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NEUROTRANSMITTERS

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  1. NEUROTRANSMITTERS

  2. Classic Characteristics: • Synthesized in the neuron. • Become localized in presynaptic terminal. • Bind to receptor site on postsynaptic membrane. • Removed by a specific mechanism from its specific site of action.

  3. Classification • Small molecule transmitters: Amino acids: Dietary amino acids. GABA Monoamines: Catecholamines. Indoleamines. • Acetylcholine.

  4. Amino Acids • Dietary: Aspartate. Glycine. • Gamma aminobutyric acid (GABA): From decarboxylation of glutamate.

  5. Monoamines • Catecholamines: Derived from tyrosine. Include: Dopamine. Norepinephrine. Epinephrine.

  6. Monoamines • Indoleamine: Derived from tryptophan. Includes: Serotonin.

  7. Glutamate • Most common excitatory neurotransmitter in the CNS. • Synthesized in mitochondria. • Inactivated by reuptake: Via nerve terminals. Via astrocytes: Convert glutamate back to glutamine. May resupply nerve terminal.

  8. Glutamate • Found in: Cerebral cortex. Striatum. Dentate gyrus (hippocampus). Cerebellum. Spinal cord. • Excitatory influences on basal nuclei.

  9. Aspartate • Found throughout brain and spinal cord. • Effects are usually excitatory.

  10. Glycine • Common inhibitory neurotransmitter. Increases chloride conductance in postsynaptic membrane. Blocked by strychnine. • Converted from serine. • Inactivated by reuptake.

  11. Glycine • Found in: Interneurons of spinal cord: Renshaw cells. Neurons of subthalamic nuclei projecting to globus pallidus.

  12. GABA • Gamma aminobutyric acid: • Most common inhibitory neurotransmitter in CNS. Increases chloride conductance. • Inactivated via reuptake: Into nerve terminals. Into glial cells.

  13. GABA • Site of action of anxiolytic drugs such as Valium and Librium. • Inhibited by penicillin: Causes over-excitation and seizure activity in brain.

  14. GABA • Found in: Granule cells of olfactory bulbs. Amacrine cells of retina. Purkinje cells and basket cells of cerebellum. Hippocampus. Basal ganglia. Numerous interneurons.

  15. GABA • GABAergic neurons of caudate nucleus and putamen project to substantia nigra and globus pallidus. • Reduced concentrations in patients with Huntington’s chorea: May contribute to presence of uncontrolled involuntary movements.

  16. Dopamine • Usually inhibitory. • Present in neurons of substantia nigra: Nigrostriatal dopaminergic pathway projects to putamen and caudate nucleus. Loss of inhibitory influences may be associated with Parkinson’s disease.

  17. Dopamine • Other pathways project to limbic system components: Malfunctioning may be associated with schizophrenia.

  18. Dopamine • Also found in: Neurons from hypothalamus to hypophysis. Retina: Role in lateral inhibition (focusing effect). Olfactory bulb.

  19. Norepinphrine • Usually inhibitory. • May be released into neuropile from axon varicosities filled with vesicles. 90 percent do not form synapses. Accounts for slow-acting and long-lasting effects following release. May enhance neuropile neuronal activity via lateral inhibition.

  20. Norepinphrine • Inactivation: Reuptake into synaptic terminal. Uptake by effector cells (with MAO and COMT). Diffusion away from site.

  21. Norepinphrine • Inactivation: Destruction: MAO: Monoamine oxidase. Intracellular. COMT: Catechol-O-methyltransferase. Extracelluar.

  22. Norepinphrine • Found in: Locus ceruleus and Lateral tegmental nuclei. Neurons to: Midbrain tectum. Thalamus, hypothalamus Cerebral cortex, Cerebellar cortex Medulla and spinal cord Most postsynaptic sympathetic neurons.

  23. Norepinphrine Functions • Modulator– sets brain tone. • Suppresses irrelevant stimuli. • Enhances relevant stimuli. • Modifies behavior, arousal, degree of alertness, ECG activity and sleep. • Role in mood, memory. • Hormone regulation and homeostasis.

  24. Norepinephrine Receptors • Alpha adrenergic receptors • Beta adrenergic receptors: Involve G-proteins and adenyl cyclase activation.

  25. Epinephrine • Usually excitatory. • Found in neurons of: Lower brainstem tegmentum. Locus ceruleus. Axons projecting rostrally to hypothalamus. Axons projecting to intermediolateral cell column of spinal cord (preganglionic sympathetic neurons located here.)

  26. Serotonin • Only present in cell bodies of neurons located primarily in the raphe and reticular formation (limited) of brainstem. • Inactivated by MAO.

  27. Serotonin • Axons project to: Diencephalon. Striatum. Cerebral cortex. Ependyma of ventricles. Cerebellum. Spinal nucleus of CN V

  28. Serotonin Functions (?) • Inducing sleep. • Pain transmission. • Certain psychotic disorders: Depression. • Total amnesia may occur when: Raphe neurons are destroyed. Serotonin stores are depleted by reserpine.

  29. Acetylcholine • Choline is made in liver, not brain. • Synthesized by choline acetyltransferase: Synthesized within neuron cell body. • Degraded by acetylcholinesterase: Synthesized within neuron cell body.

  30. Acetylcholine • Found in neurons: Lower alpha and gamma motor neurons. All ANS preganglionic neurons. All parasympathetic postganglionic neurons. Sympathetic postganglionic neurons innervating sweat glands.

  31. Acetylcholine • Found in brain: Basal nucleus of Meynert: Axons project to cerebral cortex. Alterations in these neurons may be associated with Alzheimer’s. Interneurons within striatum: Loss of these seems to be a main feature of Huntington’s. Associated with limbic system.

  32. Cholinergic Receptors • Nicotinic: Found in spinal cord and superior colliculi. Activate mainly sodium channels (EPSP). Found in neuromyal junctions. Found in autonomic ganglia. Blocked by curare.

  33. Cholinergic Receptors • Muscarinic: Predominant cholinergic receptors in brain. Principal cholinergic receptor on ANS target organs. Coupled to G-proteins. Blocked by atropine.

  34. Nitric Oxide

  35. Neuroactive Peptides • Opioid peptides: Include: Endorphins. Dynorphins. Enkephalins. Present in pain pathways. Present in limbic circuits. Present in reticular formation (enkephalins).

  36. Neuroactive Peptides • Hormones: Vasopressin (ADH). Oxytocin.

  37. Neuroactive Peptides • Somatostatin. • Tachykinins: Substance P: Excitatory transmitter in CNS and intestinal tract. Associated with pain pathways. High concentration in substantia nigra. Decreased in Huntington’s patients.

  38. Neuroactive Peptides • Vasoactive intestinal peptide (VIP) • Cholecystokinin octapeptide

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