Neurotransmission Flashcards
Otto Loewi’s Key Experiment (what was it and what did results lead to?)
- the vagus nerve was stimulated in a solution
- solution was taken and another heart was placed into it. the hear rate slowed (decreased)
- indicated that electrical transmission was not the only thing. gave hint towards existent of chemical transmission
Neurotransmitter
endogenous (produced within the organism) chemical messenger responsible for neural communication
- chemical synaptic transmission
Where is NT located?
- synthesized in the neuron (present in presynaptic axon terminals)
- receptors exist on post synaptic cell
What does NT do?
- is released in sufficient amounts when AP reaches presynaptic terminal to produce response in target cell
- exogenous (originating outside of organism) administration mimics endogenously produced NT action. By blocking the release of NT, it prevents synaptic activity from affecting postsynaptic cell
- mechanisms for removal of NT from site of activation include autoreceptors, degradation, reuptake
General Effects of NT: excitatory
- excitatory: increase likelihood of firing AP in postsynaptic cell; opens sodium channel (helps depolarize membrane potential bc it is a positively charged ion. gets less negative. could also be another positively charged ion)
- glutamate can open sodium channels
General Effects of NT: inhibitory
decreases likelihood of firing AP in postsynaptic cell
- chloride ion channel is involved (negatively charged)
- GABA
- hyperpolarized instead of depolarization
Example of how the receptor determines IPSP vs EPSP reaction
- ex: acetylcholine (ACh)
ex: acetylcholine (ACh) binds to two different types of postsynaptic receptors
- ACh can be excitatory
*opens positive ion channels (Na+ and K+) - ex: skeletal muscles
- ACh can be inhibitory
*opening negative ion channels like Cl- - ex: heart muscles
General Effects of NT: modulatory
- instead of having direct effect, you can regulate the signal across synapse.
- modulate activity of postsynaptic cell by influencing effects of chemical messengers
- usually have more widespread effect
- NT affecting larger number of diff. neurons
*widespread effect can lead have more complex effects
Classes of Receptors: ionotropic
ionotropic receptors (also called ligand-gated ion channels)
- ion channel is right in the receptor
- there is a direct alteration of the ion channel.
->thus it is fast synaptic transmission
Classes of Receptors: metabotropic
dont contain ion channel
- often are G protein-coupled receptor
- G-protein can act as a signaling molecule or can affect messengers
- indirectly alter ion channels/gene expression
- other alterations can happen in the cell: can be longer lasting and can potentially enhance signal
->generally slower than ionotropic receptors
Acetylcholine (ACh)
- was the first neurotransmitter to be identified
- made from choline and acetyl CoA
Cholinergic neurons
neurons that use ACh
cholinergic neurons projecting through basil forebrain
widespread projections from forebrain to many different regions including the cortex, hippocampus, and amygdala (effect on memory/learning)
- central in PNS
cholinergic neurons projecting through midbrain/pons
projections that are going away from the cortex (down spinal cord) may be signaling to skeletal muscles, internal organs
- central in CNS
two main sources of cholinergic neurons are in
the basil forebrain and midbrain/pons
Functions of ach
- attention, learning
- really important as a signal for onset of sleep, drowsiness, arousal, and sensory processing and intentional focus
Two types of ACh receptors: muscarinic
- G-protein coupled (metabotropic) receptors for ACh
- slower
- can be excitatory or inhibitory
Two types of ACh receptors: nicotinic (nAch)
- most are ionotropic and excitatory
- are the main types of receptors in neuromuscular junction
- are selective for positive ions (K+, Na+, Ca2+)
one of the key components of ach synthesis pathway is
choline acetyltransferase (chAT): is an enzyme that transfers acetate ion from acetyl-CoA to choline (which is gotten from food) and turns it into acetylcholine (ACh)
where is chAT enzyme found
ChAT is found in high concentration in cholinergic neurons
- both in (CNS) and (PNS)
ChAT is produced in the body of the neuron and is transported to the nerve terminal, where its concentration is highest.
ACh metabolism
- acetylcholine (ACh) made from choline and acetyl CoA
- ACh is rapidly broken down in synaptic cleft by acetylcholinesterase
- occurs quickly (breaks down molecule in 80 microseconds) - choline is transported back into the axon terminal and is used to make more ACh
acetylcholinesterase
enzyme that breaks down ACh in synaptic cleft
Myasthenia Gravis
- autoimmune disorder
- attacks receptors for nAch (nicotinic)
ex: neuromuscular junction, esp in the face. some of the symptoms would be drooping in the face, a paralyzed-like facial. first symptom would be the weakness of the eye. muscle activation is inhibited
Alzheimer’s Dementia (AD); Cholinergic Deficit Hypothesis
progressive cognitive decline
proposes that the symptoms of dementia is due to lack of Ach
death of cholinergic neurons in basal forebrain. ex: there are 500k cholinergic neurons in nucleus basilis but goes down to only 100k in advanced AD
increasing Ach levels or inhibiting Ach breakdown may result in improved cognitive function
Alzheimer’s Dementia (AD); inhibiting Ach breakdown
prob a better option because of the blood brain barrier
Popular approach for addressing AD: enhancing cholinergic transmisison
AchE inhibitors (donezepil, Aricept) to help treat AD
inhibiting AChE enzyme -> it increases Ach levels in synaptic cleft. signaling increases
help cognitive symptoms but do not alter disease progression (only 1-3 yr effect)
Where in the neuronal pathway could be intervened to increase cholinergic transmission?
Ach receptor agonists increase Ach levels in synaptic cleft
-> help cognitive symptoms
Drugs that target ChT1 enzyme (by blocking reuptake)
Serotonin 5-HT
most cells are in raphe nuclei
serotonergic fibers project widely
in implicated in sleep states, mood, sexual behavior, and anxiety
Serotonin Synthesis; diet differences
tryptophan (from food) regulates synthesis
large amino acids can compete for transport across BBB
high protein diet increases competition -> less 5-HT
high carb diet reduces competition -> more 5-HT
Serotonin Synthesis: rate limiting step
rate limiting step: availability of tryptophan hydroxylase (TPH) converts tryptophan to 5-HTP ( the chemical precursor/metabolic intermediate in biosynthesis serotonin)
Serotonin Synthesis Metabolism (MAO)
mitochondrial membrane enzyme: monoamine oxidase (MAO)
What might MAO inhibitors do to serotonin level?
MAO enzymes are involved in removing the NTs like serotonin from the brain.
MAOIs prevent removal of serotonin, which makes more of these brain chemicals available to effect changes in both cells and circuits
What do antidepressants, such as Prozac, do?
they can increase 5-HT activity by inhibiting (blocking) reuptake thus increasing serotonin in synaptic cleft which increases activation of serotonin receptors
Gastrointestinal, behavioral, and CNS effects of serotonin
GI: gastric secretion, gastrointestinal motility, intestinal secretions, colonic tone, pancreatic secretion
behavioral: visceral pain (internal organs), emotion, stress response, appetite, addiction, sexuality
CNS: motor control, circadian rhythm, cerebellum regulation, body temp, cns vascular tone
Dopamine (DA) nigrostriatal pathway
- DA found in neurons in nigrostriatal pathway
- substantia nigra origin (is affected in parkinson’s)
- targets striatum which targets motor control
- neuronal loss is a cause of Parkinson’s disease
Dopamine (DA) mesolimbocortical pathway
mesolimbocortical DA pathway
- in the ventrotechmental area (VTA- where DA is made)
- targets nucleus accumbens, hippocampus, and cortex
- is involved in how we learn reward, reinforcement learning
- abnormalities associated with schizophrenia
Dopamine synthesis
tyrosine is a precursor found in our diet -> tyrosine hydroxylase (a rate-limiting enzmye) turns tyrosine into L-DOPA -> L-DOPA is converted into dopamine
Dopamine metabolism
Monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) seen in synaptic cleft that break down DA
Norepinephrine and epinephrine synthesis
also synthesized by tyrosine
any neurons that have tyrosine hydroxylase can produce any catecholamine transmitter
Norepinephrine
released from locus coeruleus in the pons and lateral tegmental system in the midbrain
cells producing it are noradrenergic
NE systems modulate processes including mood, arousal, and sexual behavior
Epinephrine (adrenaline)
regulate sympathetic nervous system
fight or flight response
increase heart rate, blood flow, and faster breathing
