Neurotransmission

Question 1

Otto Loewi’s Key Experiment (what was it and what did results lead to?)

Answer 1

• 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

Question 2

Neurotransmitter

Answer 2

endogenous (produced within the organism) chemical messenger responsible for neural communication

• chemical synaptic transmission

Question 3

Where is NT located?

Answer 3

• synthesized in the neuron (present in presynaptic axon terminals)
• receptors exist on post synaptic cell

Question 4

What does NT do?

Answer 4

• 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

Question 5

General Effects of NT: excitatory

Answer 5

• 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

Question 6

General Effects of NT: inhibitory

Answer 6

decreases likelihood of firing AP in postsynaptic cell

• chloride ion channel is involved (negatively charged)
• GABA
• hyperpolarized instead of depolarization

Question 7

Example of how the receptor determines IPSP vs EPSP reaction

• ex: acetylcholine (ACh)

Answer 7

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

Question 8

General Effects of NT: modulatory

Answer 8

• 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

Question 9

Classes of Receptors: ionotropic

Answer 9

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

Question 10

Classes of Receptors: metabotropic

Answer 10

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

Question 11

Acetylcholine (ACh)

Answer 11

• was the first neurotransmitter to be identified
• made from choline and acetyl CoA

Question 12

Cholinergic neurons

Answer 12

neurons that use ACh

Question 13

cholinergic neurons projecting through basil forebrain

Answer 13

widespread projections from forebrain to many different regions including the cortex, hippocampus, and amygdala (effect on memory/learning)

• central in PNS

Question 14

cholinergic neurons projecting through midbrain/pons

Answer 14

projections that are going away from the cortex (down spinal cord) may be signaling to skeletal muscles, internal organs

• central in CNS

Question 15

two main sources of cholinergic neurons are in

Answer 15

the basil forebrain and midbrain/pons

Question 16

Functions of ach

Answer 16

• attention, learning
• really important as a signal for onset of sleep, drowsiness, arousal, and sensory processing and intentional focus

Question 17

Two types of ACh receptors: muscarinic

Answer 17

• G-protein coupled (metabotropic) receptors for ACh
• slower
• can be excitatory or inhibitory

Question 18

Two types of ACh receptors: nicotinic (nAch)

Answer 18

• most are ionotropic and excitatory
• are the main types of receptors in neuromuscular junction
• are selective for positive ions (K+, Na+, Ca2+)

Question 19

one of the key components of ach synthesis pathway is

Answer 19

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)

Question 20

where is chAT enzyme found

Answer 20

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.

Question 21

ACh metabolism

Answer 21

1. acetylcholine (ACh) made from choline and acetyl CoA
2. ACh is rapidly broken down in synaptic cleft by acetylcholinesterase
   - occurs quickly (breaks down molecule in 80 microseconds)
3. choline is transported back into the axon terminal and is used to make more ACh

Question 22

acetylcholinesterase

Answer 22

enzyme that breaks down ACh in synaptic cleft

Question 23

Myasthenia Gravis

Answer 23

• 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

Question 24

Alzheimer’s Dementia (AD); Cholinergic Deficit Hypothesis

Answer 24

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

Question 25

Alzheimer's Dementia (AD); inhibiting Ach breakdown

Answer 25

prob a better option because of the blood brain barrier

Question 26

Popular approach for addressing AD: enhancing cholinergic transmisison

Answer 26

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)

Question 27

Where in the neuronal pathway could be intervened to increase cholinergic transmission?

Answer 27

Ach receptor agonists increase Ach levels in synaptic cleft -> help cognitive symptoms Drugs that target ChT1 enzyme (by blocking reuptake)

Question 28

Serotonin 5-HT

Answer 28

most cells are in raphe nuclei serotonergic fibers project widely in implicated in sleep states, mood, sexual behavior, and anxiety

Question 29

Serotonin Synthesis; diet differences

Answer 29

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

Question 30

Serotonin Synthesis: rate limiting step

Answer 30

rate limiting step: availability of tryptophan hydroxylase (TPH) converts tryptophan to 5-HTP ( the chemical precursor/metabolic intermediate in biosynthesis serotonin)

Question 31

Serotonin Synthesis Metabolism (MAO)

Answer 31

mitochondrial membrane enzyme: monoamine oxidase (MAO)

Question 32

What might MAO inhibitors do to serotonin level?

Answer 32

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

Question 33

What do antidepressants, such as Prozac, do?

Answer 33

they can increase 5-HT activity by inhibiting (blocking) reuptake thus increasing serotonin in synaptic cleft which increases activation of serotonin receptors

Question 34

Gastrointestinal, behavioral, and CNS effects of serotonin

Answer 34

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

Question 35

Dopamine (DA) nigrostriatal pathway

Answer 35

- 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

Question 36

Dopamine (DA) mesolimbocortical pathway

Answer 36

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

Question 37

Dopamine synthesis

Answer 37

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

Question 38

Dopamine metabolism

Answer 38

Monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) seen in synaptic cleft that break down DA

Question 39

Norepinephrine and epinephrine synthesis

Answer 39

also synthesized by tyrosine any neurons that have tyrosine hydroxylase can produce any catecholamine transmitter

Question 40

Norepinephrine

Answer 40

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

Question 41

Epinephrine (adrenaline)

Answer 41

regulate sympathetic nervous system fight or flight response increase heart rate, blood flow, and faster breathing