Lecture 6 Flashcards
Gases - Nitric Oxide (NO)?
-Synthesized from Arginine via NO Synthase (NOS) on demand
-NOT stored in vesicles
-Released via diffusion (not exocytosis)
-NO receptors
Gases - Nitric Oxide (NO) Functions?
1) Retrograde signaling
2) Increase cGMP –> regulates Ca2+ homeostasis
3) Rapid signaling
Gases - Carbon Monoxide (CO)
-Synthesized from heme via heme oxygenase (HO) (heme –> biliverdin)
-NOT stored in vesicles
-Released via diffusion (not exocytosis)
-NO receptors
Gases - Carbon Monoxide (CO) Functions?
1) Retrograde signaling
2) Regulates cGMP –> mediates smooth muscle contraction
3) Rapid signaling
Growth Factors - BDNF and NGF?
-Constitutively synthesized and released from:
1) Soma
2) Dendrites
-Synthesized/released after depolarization at:
1) Soma
2) Dendrites
3) Nerve terminals
-Mediated interactions with low affinity and high affinity receptors
(Growth Factors - BDNF and NGF)
Constitutively synthesized and released from?
1) Soma
2) Dendrites
(Growth Factors - BDNF and NGF) Synthesized/released after depolarization at?
1) Soma
2) Dendrites
3) Nerve terminals
Growth Factors - BDNF?
-Effects:
1) Neurogenesis (making new cells)
2) Excitability
3) Brain connectivity
(Growth Factors - BDNF)
Too much?
Affects plasticity and may affect learning
(Growth Factors - BDNF)
Too little?
Affects plasticity and linked to increased depressive episodes
(Small Molecule Neurotransmitters)
Acetylcholine?
-Synthesized from choline + acetyl CoA by enzyme choline acetyltransferase (ChAT)
-Action terminated: hydrolysis by AChE
(Small Molecule Neurotransmitters)
Acetylcholine Indicated Effects and Rate-Limiting Synthetic Step?
-Indicated Effects: Involved in muscle movement as well as neuronal plasticity and memory
-Rate-Limiting Synthetic Step is high affinity choline uptake (Na+ dependent)
(Small Molecule Neurotransmitters)
Acetylcholine too much and too little?
-Too much: Muscle contractions (ex. black widow venom
-Too little: Paralysis (ex. curare and botulism toxin)
(Small Molecule Neurotransmitters)
Acetylcholine Cholinergic Circuits?
1) Basal forebrain neurons
(Degenerate in Alzheimer’s) (less of neurons)
2) Brainstem neurons (Induces REM) (positive)
ACh Neurons degenerate in Alzheimer’s disease. How would you target this pathway to help maintain its activity?
AChE Inhibitor
(Less AChE at cleft) (Get rid of enzyme that is terminating action)
(Small Molecule Neurotransmitters)
Serotonin (5-HT)?
-Synthesized from tryptophan by enzyme tryptophan hydroxylase
-Action terminated:
1) Reuptake into presynaptic terminal
2) Catabolized by MAO-A
-Rate-Limiting Synthetic Step is Tryptophan Hydroxylase
(Small Molecule Neurotransmitters)
Serotonin (5-HT)
Indicated Effects?
1) Mood control
2) Homeostasis
3) Circadian rhythms
4) Motor behaviors
5) Appetite and digestion (90% of serotonin is found in intestine)
6) State of mental arousal
(Small Molecule Neurotransmitters)
Serotonin (5-HT) too much and too little?
-Too much: Serotonin syndrome (confusion, twitching and trembling, dilated pupils, shivering, goosebumps, headache)
-Too little: Schizophrenia, depression, sleep changes
(Small Molecule Neurotransmitters)
Serotonin (5-HT)
Serotonergic Circuits?
1) Caudal Raphe Nucleus
2) Rostral Raphe Nucleus
Schizophrenia can be caused by?
-Too MUCH Dopamine
-Too LITTLE Serotonin
(Small Molecule Neurotransmitters)
Dopamine (DA)?
-Synthesized from tyrosine by enzyme tyrosine hydroxylase
-Action terminated:
1) Reuptake into pre/post-synaptic terminal
-Rate-Limiting Synthetic Step is tyrosine hydroxylase
(Small Molecule Neurotransmitters)
Dopamine (DA) too much and too little?
-Too much: Schizophrenia
-Too little: Parkinson’s disease
(Small Molecule Neurotransmitters)
Dopamine (DA) Dopaminergic Circuits?
1) Ventral Tegmental Area (VTA)
-Important for goal-oriented/reward behaviors
-Activated by drugs of abuse
2) Substantia Nigra
-Degenerate in Parkinson’s disease
-Control posture and movement
(Motivation: Wanting vs. Liking) Serotonin?
-Key factor in liking
-Mood stabilizer, wellbeing, happiness
(Motivation: Wanting vs. Liking) Dopamine?
-Key factor in wanting
-Motivational role in Brain’s reward system
(Small Molecule Neurotransmitters) Norepinephrine (NE)?
-Dopamine synthesized from tyrosine by enzyme tyrosine hydroxylase
-Dopamine transported into vesicle by VMAT2
-Dopamine beta-hydroxylation (DbetaH) to NE
-Action Terminated:
1) Reuptake into pre-synaptic terminal
2) Catabolized by MAG-A and COMT
-Rate-Limiting Synthetic Step is tyrosine hydroxylase
NE stems from another neurotransmitter?
Dopamine
(Small Molecule Neurotransmitters) Norepinephrine (NE)
Indicated Effects?
1) Influences sleep and wakefulness
2) Alertness/attention (“fight or flight”)
3) Arousal
4) Readiness for action
(Small Molecule Neurotransmitters) Norepinephrine (NE) too much and too little?
-Too much: Increased BP, anxiety, sweating, headaches
-Too little: lethargy, lack of focus, depression
(Small Molecule Neurotransmitters) Norepinephrine (NE)
Noradrenergic Circuits?
1) Locus Coeruleus
(Small Molecule Neurotransmitters) Glutamate (Glu)?
-Dopamine synthesized from glutamine by enzyme glutaminase
-Transported into vesicle by VGLUT
-Action terminated:
1) Sodium-dependent uptake into neurons and astrocytes (Excitatory amino acid transporter (EAAT))
-Rate-Limiting Synthetic Step is Glutaminase
(Small Molecule Neurotransmitters) Glutamate (Glu)
Glutaminergic Circuits?
Widespread
(Small Molecule Neurotransmitters) Glutamate (Glu)
Indicated Effects?
1) Main excitatory neurotransmitter
2) Role in synaptic plasticity, learning and memory
3) Important role in seizures
(Small Molecule Neurotransmitters) Glutamate (Glu) too much and too little?
-Too much: excitotoxicity and seizures
-Too little: psychosis, coma and death
(Small Molecule Neurotransmitters)
GABA?
-GABA synthesized from glutamate by enzyme glutamic acid decarboxylase (GAD)
-Action terminated:
1) Sodium-depends uptake into neurons and astrocytes (GABA transporter (GAT))
2) Catabolized by GABA transaminase
-Rate-Limiting Step is Glutamic Acid Decarboxylase (GAD)
(Small Molecule Neurotransmitters) GABA Indicated Effects?
1) Main inhibitory neurotransmitter
2) Motor control and vision
3) Anxiolytic, Anticonvulsant
4) Pain
(Small Molecule Neurotransmitters) GABA Circuits?
Widespread
(Small Molecule Neurotransmitters) GABA too much and too little?
-Too much: over-sedation, over-relaxing of muscles including heart and respiration
-Too little: Anxiety, seizures
GABA is opposite of?
Glutamate
Clinical Applications?
-Baclofen (Lioresal) (Agonist of GABAb receptors) (relax muscles, improves movement and relieves pain)
-Ketamine (Antagonist of NMDA (Glutamate) receptor) (numbing of pain and sedation, feeling of distance from body)
