ST 4.1: Intro to Transmitters + Ach

What is a neurotransmitter?

A chemical substance that transmits a signal from one to another.

What is a neuromodifier?

A chemical that modifies the characteristics of synaptic transmission.

Criteria 1 for establishing a NT

Presence: It must be present in the presynaptic neuron or vesicles.

Criteria 2 for establishing a NT

Identity of Action: When applied to post-synaptic cells, it must produce the same effect as stimulating the presynaptic nerve.

Criteria 3 for establishing a NT

Release: It must be released from the presynaptic nerve upon stimulation

Criteria 4 for establishing a NT

Synthesis: It must be synthesized within the presynaptic nerve upon stimulation.

Criteria 5 for establishing a NT

Termination: There must be a mechanism (enzymatic or reuptake) to end its action.

Criteria 6 for establishing a NT

Its action should be predictably influenced by drugs that affect receptor binding.

What is a Type 1 NT?

Small, charged chemicals uniquely synthesized in nerve terminals.

Examples of Type 1 NT

Ach, Catecholamines, GABA

What is a Type 2 NT?

Small, charged; present in every cell but uniquely packaged into vesicles by neurons.

Examples of Type 2 NT

Glutamate, Glycine, Aspartate

What is a Type 3 NT?

Large molecules; synthesized in cell bodies based on gene expression

Example of Type 3 NT?

LHRH

What is a type 4 NT?

Small molecules that diffuse across membranes; no traditional receptors; activate intracellular proteins.

Example of Type 4 NT?

NO, CO

What is the synthesis of Acetylcholine?

Choline + Acetyl CoA --(ChAT)--> Acetylcholine

What is the source of choline?

Diet

How is choline transported into Ach terminals?

High Affinity Choline Uptake Transporter

What is the rate limiting step in synthesis of Ach?

High Affinity Choline Uptake Transporter

How is Ach synthesis regulated?

Action Potentials cause synaptic vesicles to fuse with the membrane, inserting more choline transporters and increasing synthesis to meet demand.

How is Ach concentrated into vesicles?

By a transporter powered by a proton-dependent ATPase.

How is Ach terminated?

Acetylcholinesterase breaks Ach down into choline and acetate.

How much of the resulting choline is transported back into the terminal for reuse?

50%

What are CNS cholinergic systems primarily linked to?

Learning, Memory, Cognition, Attention, and Arousal

Where is one of the major cholinergic hubs?

Basal Forebrain

What happens to Ach, ChAT, and HACU in the cortex and hippocampus in AD patients?

Dramatic Decrease

What happens to the number of cholinergic cells in the basal forebrain in AD patients?

Decrease

How is mild AD treated?

Achase inhibitors (do not stop disease progression)

Other AD pathology includes

neurofibrillary tangles and amyloid plaques.