Neurotransmitters

Monoamines as Neurotransmitters

Monoamine Neurotransmitters Monoamines are regulatory molecules derived from amino acids. CATECHOLAMINES: these are tyrosine derivatives: dopamine, norepinephrine, epinephrine. Bind to adrenergic receptors. Norepinephrine is a neurotransmitter and hormone but epinephrine is primarily a hormone tyrosine tyrosine Other monoamines: 2) SEROTONIN (derived from tryptophan) 3) Histamine (derived from histidine)

Norepinephrine as a neurotransmitter Used in both the CNS and PNS Sympathetic neurons use norepinephrine on smooth muscles, cardiac muscles, and glands. Used by neurons of the CNS in brain regions associated with arousal Amphetamines work by stimulating norepinephrine pathways in the brain.

Monoamine Action and Inactivation KNOW THIS PATHWAY

Monoamines use G-protein Coupled Channels THIS IS A SECOND MESSENGER SYSTEM This is a BETA ADRENERGIC receptor. Sympathetic neurons of the PNS use norepinephrine as their neurotransmitter.

Serotonin as a neurotransmitter Used by neurons in the raphe nuclei (middle region of brainstem) Implicated in mood, behavior, appetite, and cerebral circulation The drug LSD and other hallucinogenic drugs may be agonists. Serotonin specific reuptake inhibitors (SSRIs) are used to treat depression. Prozac, Paxil, Zoloft Over a dozen known receptors allow for diversity of serotonin function. Different drugs that target specific serotonin receptors could be given for anxiety, appetite control, and migraine headaches. serotonin

Dopamine as a neurotransmitter Neurons that use dopamine (dopaminergic neurons) are highly concentrated in the midbrain in two main areas: Nigrostriatal dopamine system: involved in motor control Mesolimbic dopamine system: involved in emotional reward Nigrostriatal – axons coming from substantia nigra --> basal ganglia Mesolimbic – axons coming from vental tegmental area  nucleus accumbens and prefrontal cortex dopamine

Nigrostriatal dopamine system: (motor) Parkinson disease is caused by degeneration of these neurons. Patients are treated with L-dopa and monoaminoxidase inhibitors Activates the substantia nigra brain region. dopamine

Mesolimbic dopamine system involved in emotional reward. Schizophrenia is associated with too much dopamine. Dopamine antagonists are used to treat schizophrenia Activates the limbic system. Associated with addictions to nicotine, alcohol, other drugs dopamine

Abused because it elevates energy/mood Crosses the blood-brain barrier Cocaine Abused because it elevates energy/mood Crosses the blood-brain barrier In mesolimbic reward system, it is a triple-reuptake inhibitor: Blocks reuptake of dopamine Blocks reuptake of serotonin Blocks reuptake of norepinephrine Danger: Blocks Na+ ion channels Raises heart rate/blood pressure Increase risk of stroke, seizure

Other Neurotransmitters

Amino acids as NTs Excitatory NT – glutamate and aspartate Glutamate – major excitatory neurotransmitter Produces EPSPs in 80% of synapses in cortex Constitutes major energy use in the brain Involved in memory Astrocytes take glutamate from the synaptic cleft to maintain homeostasis glutamate

Inhibitory NTs Glycine produces IPSPs Binding of glycine opens Cl− channels, causing an influx of Cl−. Makes it harder to reach threshold Important in the spinal cord for regulating skeletal muscle movement. This allows antagonistic muscle groups to relax while others are contracting (e.g. biceps relax while triceps contract).

GABA , another inhibitory neurotransmitter Gamma-aminobutyric acid most common neurotransmitter in the brain used by 1/3 of the brain’s neurons. inhibitory, opens Cl− channels involved in motor control. Degeneration of GABA-secreting neurons in the cerebellum results in Huntington disease.

GABA receptors contain a chloride channel

Nitric Oxide Nitric oxide (not nitrous oxide laughing gas) A gas produced by some neurons in the CNS and PNS from the amino acid L-arginine Diffuses across the presynaptic axon plasma membrane (no vesicle) Diffuses into the target cell and activates the production of cGMP as a second messenger Causes blood vessel dilation (Viagra works by stimulating the action of nitric oxide) and helps kill bacteria May also act as a retrograde NT

Summation: Spatial Spatial summation occurs due to convergence of signals onto a single postsynaptic neuron. All of the EPSPs and IPSPs are added together at the axon hillock.

Summation: Temporal Temporal summation is due to successive waves of neurotransmitter release that add together at the initial segment of the axon.