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: Dietary amino acids.

GABA Monoamines: Catecholamines.

Indoleamines.

 Acetylcholine.

Amino Acids

 Dietary: Aspartate.

Glycine.

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

Monoamines

 Catecholamines: Derived from tyrosine.

Include: Dopamine.

Norepinephrine.

Epinephrine.

Monoamines

 Indoleamine: Derived from tryptophan.

Includes: Serotonin.

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.

Glutamate

 Found in: Cerebral cortex.

Striatum.

Dentate gyrus (hippocampus).

Cerebellum.

Spinal cord.

 Excitatory influences on basal nuclei.

Aspartate

 Found throughout brain and spinal cord.

 Effects are usually excitatory.

Glycine

 Common inhibitory neurotransmitter.

Increases chloride conductance in postsynaptic membrane.

Blocked by strychnine.

 Converted from serine.

 Inactivated by reuptake.

Glycine

 Found in: Interneurons of spinal cord: Renshaw cells.

Neurons of subthalamic nuclei projecting to globus pallidus.

GABA

 Gamma aminobutyric acid:  Most common inhibitory neurotransmitter in CNS.

Increases chloride conductance.

 Inactivated via reuptake: Into nerve terminals.

Into glial cells.

GABA

 Site of action of anxiolytic drugs such as Valium and Librium.

 Inhibited by penicillin: Causes over-excitation and seizure activity in brain.

GABA

 Found in: Granule cells of olfactory bulbs.

Amacrine cells of retina.

Purkinje cells and basket cells of cerebellum.

Hippocampus.

Basal ganglia.

Numerous interneurons.

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.

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.

Dopamine

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

Dopamine

 Also found in: Neurons from hypothalamus to hypophysis.

Retina: Role in lateral inhibition (focusing effect).

Olfactory bulb.

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.

Norepinphrine

 Inactivation: Reuptake into synaptic terminal.

Uptake by effector cells (with MAO and COMT).

Diffusion away from site.

Norepinphrine

 Inactivation: Destruction: MAO: COMT: Monoamine oxidase.

Intracellular.

Catechol-O-methyltransferase.

Extracelluar.

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.

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.

Norepinephrine Receptors

 Alpha adrenergic receptors  Beta adrenergic receptors: Involve G-proteins and adenyl cyclase activation.

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.)

Serotonin

 Only present in cell bodies of neurons located primarily in the raphe and reticular formation (limited) of brainstem.

 Inactivated by MAO.

Serotonin

 Axons project to: Diencephalon.

Striatum.

Cerebral cortex.

Ependyma of ventricles.

Cerebellum.

Spinal nucleus of CN V

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.

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.

Acetylcholine

 Found in neurons: Lower alpha and gamma motor neurons.

All ANS preganglionic neurons.

All parasympathetic postganglionic neurons.

Sympathetic postganglionic neurons innervating sweat glands.

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.

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.

Cholinergic Receptors

 Muscarinic: Predominant cholinergic receptors in brain.

Principal cholinergic receptor on ANS target organs.

Coupled to G-proteins.

Blocked by atropine.

Nitric Oxide

Neuroactive Peptides

 Opioid peptides: Include: Endorphins.

Dynorphins.

Enkephalins.

Present in pain pathways.

Present in limbic circuits.

Present in reticular formation (enkephalins).

Neuroactive Peptides

 Hormones: Vasopressin (ADH).

Oxytocin.

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.

Neuroactive Peptides

 Vasoactive intestinal peptide (VIP)  Cholecystokinin octapeptide