PSY 241 Lecture 5 and 6

• Synthesized in the neuron
• Present in the presynaptic terminal
• Released when action potential reaches terminals
• Recognized by specific receptors and causes a change in posynaptic cell
• Inactivated

Acetylcholine (first discovered)

• Amino acids (most numerous)
• -Glutamate (excitatory)
• -gamma-amino butyric acid (GABA) (inhibitory)

• Monoamines (derived from an amino acid)
• -catecholamines
• epinephrine (adrenaline)
• norepinephrine (noradrenaline)
• dopamine
• -indoleamines
• serotonin
• melatonin

• Soluble gases
• nitric oxide
• carbon monoxide

• Occurs in presynaptic terminal from choline, which comes mainly from fat in our diet
• Acetyl CoA and Choline converted to Acetylcholine by the enzyme Choline Aceytltransferase (ChAT)
• Choline is rate limiting step - determines overall rate of synthesis

In the nuclei within the basal forebrain

• Synapses are called cholinergic
• Acetylcholine is a neurotransmitter released to affect activity of other neurons in the brain, internal organs (e.x. heart, lungs, stomach), or muscles.

• Nicotonic (ionotropic) and muscarinic (metabotropic)
• Nicotinic receptors all the passage of sodium (Na+)
• Binding of nicotinic receptors by acetylcholine causes depolarization.

Acetylcholine is terminated by acetylcholinesterase (AChE) in the synaptic cleft which converts acetylcholine into choline and acetate (both of which are transported back into the cell)

• At neuromuscular junction, acetylcholine causes muscle contractions
• At internal organs, acetylcholine decreases activity
• In CNS, involved in learning and memory, Alzheimer's, and sleep

• Decreasing acetylcholine at the neuromuscular junction will cause paralysis
• Dermatologists use botulinum toxin (Botox) for cosmetic purposes
• Botox blocks acetylcholine release from incoming motor nerve fibers

• Occurs in presynaptic terminal
• Glutamine is converted into Glutamate by Glutaminase

• Synapses are called glutamatergic
• Glutamate is released to excite (stimulate) other neurons

• Glutamate binds to both ionotropic (NMDA, AMPA, and Kainate) and metabotropic (mGluR1 -mGluR8) receptors
• NMDA, AMPA, and Kainate allow the passage of sodium (Na+) and as a result ________ occurs when glutamate binds to there receptors
• NMDA also allows the passage of Calcium (Ca++), which activated second messengers within the cell

• Glutamate is terminated by reuptake, primarily by Astrocytes, which take up the glutamate and convert glutamate back to glutamine by glutamine synthetase
• High levels of glutamate in the extracellular fluid are dangerous, producing excessive neuronal excitation and even cell death

• Main excitatory neurotransmitter in the central nervous system (EPSPs)
• Learning and memory is also dependent on glutamatergic activity at the NMDA receptor
• Block the NMDA receptor and animals do not perform well on a test of memory

• Occurs in presynaptic terminal
• Glutamate is converted into GABA by Glutamate decarboxylase

• Synapses are called GABAergic
• GABA is released to affect activity of other neurons

• GABA binds to 2 main receptors: GABA_A (ionotropic) and GABA_B (metabotropic)
• GABA_A allows the passage of Chloride (Cl-) and as a result hyperpolarization occurs when GABA binds to the receptor
• There are multiple binding sites on the GABA_A receptor (not just the one for GABA)

GABA terminated by reuptake by neurons and astrocytes, which take up the GABA and convert it eventually to succinate and glutamate (which can be used to make more GABA) by GABA aminotransferase (GABA-T).

• Main inhibitory neurotransmitter in the CNS (IPSPs)
• Enhancing activity of GABA has several effects:
• Anxiolytic (reduce anxiety)
• Sedative-hypnotic (sedation and sleep inducing)
• Anticonvulsant (reduce convulsions)

• When benzodiazepine (BDZ) drugs (e.g., Xanax) bind to the GABAA receptor, it potentiated the effect of GABA
• BDZ drugs produce anxyolytic effects

Less benzodiazepine sites

• Occurs in presynaptic terminal from Tyrosine (amino acid)
• Tyrosine hydroxylase is the rate limiting step

• Dopaminergic cell bodies are not widely distributed in the brain
• 2 main clusters of cell bodies that release dopmine: ventral tegmental area and substantia nigris
• Norepinephrine cell bodies are found in the locus coeruleus

• Synapses are called Dopaminergic or Adrenergic
• Dopamine release to affect activity of other neurons
• Norepinephrine is a neurotransmitter released to affect other neurons, but it is also released to affect activity of internal organs (e.g., heat, lungs, stomach)

• All receptors are metabotropic 
• Dopamine receptors (D1-D5)
• Norepinephrine receptors (alpha and beta)

• Inactivation of Dopamine and Norepinephrine is by reuptake into the presynaptic terminal and destruction by Monoamine Oxidase (MAO) in the cytoplasm
• Dopamine and Norepinephrine may also be destroyed by Catechol-O-methyl transferase (COMT) in the synaptic cleft. However reuptake and destruction by _______.

• Dopamine in the brain is involved in voluntary movement, motivation, and reward and disruptions in dopamine are associated with Schizophrenia and Parkinson's Disease
• In CNS, norepinephrine is involved in arousal, alertness, eating and mood
• In PNS, norepinephrine increases activity of internal organs (e.g., increase heart rate)

• Rhythmic tremor
• Learning forward
• Muscle rigidity
• Difficulty rising

• Degeneration of dopaminergic neurons from the sunstantia nigria is associated with Parkinson's Disease
• Loss of cells results in a decreased amount of dopamine sent to the basal ganglia (caudate, putamen, globus pallidus) which control voluntary movement

• Occurs in presynaptic terminal from Trytophan (amino acid)
• Tryptophan hydroxylase is the rate limiting sstep

Cells bodies are found in the raphe nuclei

• Synapses and called Serotonergic
• Serotonin is released to affect activity of other neurons

• Large family of receptors (at least 15)
• Most are metabotropic receptors, but there are ionotropic receptors

Inactivation of Serotonin is by reuptake into the presynaptic terminal and destruction by only Monoamine Oxidase (MAO) in the cytoplasm

• Activity of Serotonin has been implicated in:
• Depression and Anxiety
• Obesity
• Addiction
• Impulsivity

• Function as neurotransmitters
• Synthesis occurs in soma (require transcription and translation)
• Function as neuromodulators (chemical that regulated release of other neurotransmitters)

• Endorphins
• Primary peptide is β-endorphin---released in response to stress and mediates pain relief and eurphoria

• Enkephalins
• Widely distributed throughout CNS and interneurons especially those mediating pain pathways

• Dynorphins
• Widely distributed in the CNS and especially associated with spinal cord mediated pain pathways

• Neurotransmitters travel short distances before reaching their target
• Cellular communication: releases hormones into blood stream
• Hormone: chemical produced by endocrine glands
• Endocrine system: glands that release hormones into blood stream

Release of hormone acts to promote its further release

Oxytocin - Uterine contractions

Release of hormone acts to inhibit its subsequent release

Cortisol - stress response