NEUROTRANSMITTERSNEUROTRANSMITTERS

Classic Characteristics: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 Bind to receptor site on postsynaptic

membrane.membrane.Removed by a specific mechanism from Removed by a specific mechanism from

its specific site of action.its specific site of action.

ClassificationClassificationSmall molecule transmitters:Small molecule transmitters:

Amino acids:Amino acids:Dietary amino acids.Dietary amino acids.GABAGABA

Monoamines:Monoamines:Catecholamines.Catecholamines.Indoleamines.Indoleamines.

Acetylcholine.Acetylcholine.

Amino AcidsAmino AcidsDietary:Dietary:

Aspartate.Aspartate.Glycine.Glycine.

Gamma aminobutyric acid (GABA):Gamma aminobutyric acid (GABA):From decarboxylation of glutamate.From decarboxylation of glutamate.

MonoaminesMonoaminesCatecholamines:Catecholamines:

Derived from tyrosine.Derived from tyrosine.Include:Include:

Dopamine.Dopamine.Norepinephrine.Norepinephrine.Epinephrine.Epinephrine.

MonoaminesMonoamines Indoleamine:Indoleamine:

Derived from tryptophan.Derived from tryptophan.Includes:Includes:

Serotonin.Serotonin.

GlutamateGlutamateMost common excitatory neurotransmitter Most common excitatory neurotransmitter

in the CNS.in the CNS.Synthesized in mitochondria.Synthesized in mitochondria. Inactivated by reuptake:Inactivated by reuptake:

Via nerve terminals.Via nerve terminals.Via astrocytes:Via astrocytes:

Convert glutamate back to glutamine.Convert glutamate back to glutamine.May resupply nerve terminal.May resupply nerve terminal.

GlutamateGlutamateFound in:Found in:

Cerebral cortex.Cerebral cortex.Striatum.Striatum.Dentate gyrus (hippocampus).Dentate gyrus (hippocampus).Cerebellum.Cerebellum.Spinal cord.Spinal cord.

Excitatory influences on basal nuclei.Excitatory influences on basal nuclei.

AspartateAspartateFound throughout brain and spinal cord.Found throughout brain and spinal cord.Effects are usually excitatory.Effects are usually excitatory.

GlycineGlycineCommon inhibitory neurotransmitter.Common inhibitory neurotransmitter.

Increases chloride conductance in Increases chloride conductance in postsynaptic membrane.postsynaptic membrane.

Blocked by strychnine.Blocked by strychnine.Converted from serine.Converted from serine. Inactivated by reuptake.Inactivated by reuptake.

GlycineGlycineFound in:Found in:

Interneurons of spinal cord:Interneurons of spinal cord:Renshaw cells.Renshaw cells.

Neurons of subthalamic nuclei projecting Neurons of subthalamic nuclei projecting to to globus pallidus.globus pallidus.

GABAGABAGamma aminobutyric acid:Gamma aminobutyric acid:Most common inhibitory neurotransmitter Most common inhibitory neurotransmitter

in CNS.in CNS.Increases chloride conductance.Increases chloride conductance.

Inactivated via reuptake:Inactivated via reuptake:Into nerve terminals.Into nerve terminals.Into glial cells.Into glial cells.

GABAGABASite of action of anxiolytic drugs such as Site of action of anxiolytic drugs such as

Valium and Librium.Valium and Librium. Inhibited by penicillin:Inhibited by penicillin:

Causes over-excitation and seizure activity Causes over-excitation and seizure activity in in brain.brain.

GABAGABAFound in:Found in:

Granule cells of olfactory bulbs.Granule cells of olfactory bulbs.Amacrine cells of retina.Amacrine cells of retina.Purkinje cells and basket cells of Purkinje cells and basket cells of

cerebellum.cerebellum.Hippocampus.Hippocampus.Basal ganglia.Basal ganglia.Numerous interneurons.Numerous interneurons.

GABAGABAGABAergic neurons of caudate nucleus GABAergic neurons of caudate nucleus

and putamen project to substantia nigra and putamen project to substantia nigra and globus pallidus.and globus pallidus.

Reduced concentrations in patients with Reduced concentrations in patients with Huntington’s chorea:Huntington’s chorea:

May contribute to presence of uncontrolled May contribute to presence of uncontrolled involuntary movements.involuntary movements.

DopamineDopamineUsually inhibitory.Usually inhibitory.Present in neurons of substantia nigra:Present in neurons of substantia nigra:

Nigrostriatal dopaminergic pathway Nigrostriatal dopaminergic pathway projects projects to putamen and caudate to putamen and caudate nucleus.nucleus.

Loss of inhibitory influences may be Loss of inhibitory influences may be associated with Parkinson’s disease.associated with Parkinson’s disease.

DopamineDopamineOther pathways project to limbic system Other pathways project to limbic system

components:components:Malfunctioning may be associated with Malfunctioning may be associated with

schizophrenia.schizophrenia.

DopamineDopamineAlso found in:Also found in:

Neurons from hypothalamus to Neurons from hypothalamus to hypophysis.hypophysis.

Retina:Retina:Role in lateral inhibition (focusing effect).Role in lateral inhibition (focusing effect).

Olfactory bulb.Olfactory bulb.

NorepinphrineNorepinphrineUsually inhibitory.Usually inhibitory.May be released into neuropile from axon May be released into neuropile from axon

varicosities filled with vesicles.varicosities filled with vesicles.90 percent do not form synapses.90 percent do not form synapses.Accounts for slow-acting and long-lasting Accounts for slow-acting and long-lasting

effects following release.effects following release.May enhance neuropile neuronal activity May enhance neuropile neuronal activity

via via lateral inhibition.lateral inhibition.

NorepinphrineNorepinphrine Inactivation:Inactivation:

Reuptake into synaptic terminal.Reuptake into synaptic terminal.Uptake by effector cells (with MAO and Uptake by effector cells (with MAO and

COMT).COMT).Diffusion away from site.Diffusion away from site.

NorepinphrineNorepinphrine Inactivation:Inactivation:

Destruction:Destruction:MAO:MAO:

Monoamine oxidase.Monoamine oxidase.

Intracellular.Intracellular.

COMT:COMT:

Catechol-O-methyltransferase.Catechol-O-methyltransferase.Extracelluar.Extracelluar.

NorepinphrineNorepinphrine Found in:Found in:

Locus ceruleus and Lateral tegmental nuclei.Locus ceruleus and Lateral tegmental nuclei.Neurons to:Neurons to:Midbrain tectum.Midbrain tectum.Thalamus, hypothalamusThalamus, hypothalamusCerebral cortex, Cerebellar cortexCerebral cortex, Cerebellar cortexMedulla and spinal cordMedulla and spinal cordMost postsynaptic sympathetic Most postsynaptic sympathetic neurons.neurons.

Norepinphrine FunctionsNorepinphrine FunctionsModulator– sets brain tone.Modulator– sets brain tone.Suppresses irrelevant stimuli.Suppresses irrelevant stimuli.Enhances relevant stimuli.Enhances relevant stimuli.Modifies behavior, arousal, degree of Modifies behavior, arousal, degree of

alertness, ECG activity and sleep.alertness, ECG activity and sleep.Role in mood, memory.Role in mood, memory.Hormone regulation and homeostasis.Hormone regulation and homeostasis.

Norepinephrine ReceptorsNorepinephrine ReceptorsAlpha adrenergic receptorsAlpha adrenergic receptorsBeta adrenergic receptors:Beta adrenergic receptors:

Involve G-proteins and adenyl cyclase Involve G-proteins and adenyl cyclase activation.activation.

EpinephrineEpinephrineUsually excitatory.Usually excitatory.Found in neurons of:Found in neurons of:

Lower brainstem tegmentum.Lower brainstem tegmentum.Locus ceruleus.Locus ceruleus.Axons projecting rostrally to Axons projecting rostrally to

hypothalamus.hypothalamus.Axons projecting to intermediolateral cell Axons projecting to intermediolateral cell

column of spinal cord (preganglionic column of spinal cord (preganglionic sympathetic neurons located here.)sympathetic neurons located here.)

SerotoninSerotoninOnly present in cell bodies of neurons Only present in cell bodies of neurons

located primarily in the raphe and reticular located primarily in the raphe and reticular formation (limited) of brainstem.formation (limited) of brainstem.

Inactivated by MAO.Inactivated by MAO.

SerotoninSerotoninAxons project to:Axons project to:

Diencephalon.Diencephalon.Striatum.Striatum.Cerebral cortex.Cerebral cortex.Ependyma of ventricles.Ependyma of ventricles.Cerebellum.Cerebellum.Spinal nucleus of CN VSpinal nucleus of CN V

Serotonin Functions (?)Serotonin Functions (?) Inducing sleep.Inducing sleep.Pain transmission.Pain transmission.Certain psychotic disorders:Certain psychotic disorders:

Depression.Depression.Total amnesia may occur when:Total amnesia may occur when:

Raphe neurons are destroyed.Raphe neurons are destroyed.Serotonin stores are depleted by Serotonin stores are depleted by

reserpine.reserpine.

AcetylcholineAcetylcholineCholine 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.Synthesized within neuron cell body.Degraded by acetylcholinesterase:Degraded by acetylcholinesterase:

Synthesized within neuron cell body.Synthesized within neuron cell body.

AcetylcholineAcetylcholineFound in neurons:Found in neurons:

Lower alpha and gamma motor neurons.Lower alpha and gamma motor neurons.All ANS preganglionic neurons.All ANS preganglionic neurons.All parasympathetic postganglionic All parasympathetic postganglionic

neurons.neurons.Sympathetic postganglionic neurons Sympathetic postganglionic neurons

innervating sweat glands.innervating sweat glands.

AcetylcholineAcetylcholineFound in brain:Found in brain:

Basal nucleus of Meynert:Basal nucleus of Meynert:Axons project to cerebral cortex.Axons project to cerebral cortex.Alterations in these neurons may be Alterations in these neurons may be associated with Alzheimer’s.associated with Alzheimer’s.

Interneurons within striatum:Interneurons within striatum:Loss of these seems to be a main feature Loss of these seems to be a main feature

of of Huntington’s.Huntington’s.Associated with limbic system.Associated with limbic system.

Cholinergic ReceptorsCholinergic ReceptorsNicotinic:Nicotinic:

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

Cholinergic ReceptorsCholinergic ReceptorsMuscarinic:Muscarinic:

Predominant cholinergic receptors in brain.Predominant cholinergic receptors in brain.Principal cholinergic receptor on ANS Principal cholinergic receptor on ANS

target target organs.organs.Coupled to G-proteins.Coupled to G-proteins.Blocked by atropine.Blocked by atropine.

Nitric OxideNitric Oxide

Neuroactive PeptidesNeuroactive PeptidesOpioid peptides:Opioid peptides:

Include:Include:Endorphins.Endorphins.Dynorphins.Dynorphins.Enkephalins.Enkephalins.

Present in pain pathways.Present in pain pathways.Present in limbic circuits.Present in limbic circuits.Present in reticular formation Present in reticular formation

(enkephalins).(enkephalins).

Neuroactive PeptidesNeuroactive PeptidesHormones:Hormones:

Vasopressin (ADH).Vasopressin (ADH).Oxytocin.Oxytocin.

Neuroactive PeptidesNeuroactive PeptidesSomatostatin.Somatostatin.Tachykinins:Tachykinins:

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

Neuroactive PeptidesNeuroactive PeptidesVasoactive intestinal peptide (VIP)Vasoactive intestinal peptide (VIP)Cholecystokinin octapeptideCholecystokinin octapeptide