Behavioral Neuroscience, lecture on Aplysia and Acetylcholine (ACh)
Siphon Withdrawal
VII. Acetylcholine (ACh)
A. substrates: choline and acetyl CoA
(diet) (Glycolysis and Kreb's)
1. synthetic enzyme: choline acetyltransferase (CAT)
a. cytosolic (most is synaptic)
i. vesicular transporter = vAChT necessary
(1) package ACh for synaptic release
b. CoA left over
2. degradative enzyme: acetylcholine esterase (AChE)
a. membrane protein
b. catabolites = choline and acetate
i. reuptake of choline
c. turnover = 150ms or 5,000 ACh molecules/s
B. Muscarinic and Nicotinic Receptors (membrane proteins)
1. muscarinic M1 - M5 7tm
a. slow response time (100 - 250 ms)
b. act directly on ion channels
i. open or close K+, Ca++, or Cl- channels
(1) may lead to depolarization
or hyperpolarization
c. and activate 2nd messenger system (via G proteins)
i. M1,3,5 Gp(q)® Ý PLC ® PIP2 ®IP3 & Ca++
®DG® ÝPKC
ii. M2,4 Gi® ß AC ... ß cAMP ... ß PKA
2. Nicotinic
a. four glycosylated peptide chains a, b, g, d in muscle
b. neuronal only a & b
c. ACh binds to the a subunit
i. binding causes conformational change
1) allows cations, not anions, to pass
d. in muscle, ACh-Nicotinic binding opens cation channel, Na+ depolarizes cell membrane
i. depolarization travels down T-tubules to sarcoplasmic reticulum, releasing Ca++
1) Ca++ stimulates muscular contraction of longitudinal,
oblique, circumferential, and dorsoventral musculature
C. Central ACh Distribution in vertebrates: Involved in Learning
1. ACh is produced in the nucleus basalis
a. projections to the cerebral cortex and many parts of the brain
b. these cells degenerate during Alzheimer's disease
2. ACh is in 2 specific populations in the limbic system
a. septum to hippocampus & habenulo-endopeduncular projections
b. short axon striatal cells
D. Autonomic NS
1. all sympathetic and parasympathetic preganglionic neurons
2. parasympathetic postganglionic neurons
E. ACh as a transmitter for motor actions and coordination
1. motor neurons
\ all skeletal neuromuscular junctions
a. Invertebrates
i. Leech L, VE, DE, AE, HE
ii. Aplysia gill and siphon retraction
b. Vertebrates motoneurons of the spinal cord
2. Cells in the caudate-putamen nucleus involved in motor coordination
3. PPT and LPT innervation of substantia nigra