2. NEUROTRANSMITTERS

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

4. Classification Small molecule transmitters: Small molecule transmitters: Amino acids: Dietary amino acids. GABAMonoamines:Catecholamines.Indoleamines. Acetylcholine. Acetylcholine.

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

6. Monoamines Catecholamines: Catecholamines: Derived from tyrosine. Include:Dopamine.Norepinephrine.Epinephrine.

7. Monoamines Indoleamine: Indoleamine: Derived from tryptophan. Includes:Serotonin.

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

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

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

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

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

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

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

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

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

17. Dopamine Usually inhibitory. Usually inhibitory. Present in neurons of substantia nigra: 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.

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

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

20. Norepinphrine Usually inhibitory. Usually inhibitory. May be released into neuropile from axon varicosities filled with vesicles. 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.

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

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

23. Norepinphrine Found in: 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.

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

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

26. Epinephrine Usually excitatory. Usually excitatory. Found in neurons of: 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.)

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

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

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

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

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

32. Acetylcholine Found in brain: 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.

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

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

35. Nitric Oxide

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

37. Neuroactive Peptides Hormones: Hormones: Vasopressin (ADH). Oxytocin.

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

39. Neuroactive Peptides Vasoactive intestinal peptide (VIP) Vasoactive intestinal peptide (VIP) Cholecystokinin octapeptide Cholecystokinin octapeptide