The role of basal acetylcholine release on neuronal activity in the medial habenula

Session Number

MEDH 51

Advisor(s)

Dr. Christian J Peters, University of Illinois Chicago

Discipline

Medical and Health Sciences

Start Date

17-4-2025 2:45 PM

End Date

17-4-2025 3:00 PM

Abstract

Nicotine is an addictive chemical that leads to tolerance and withdrawal and acts as an agonist for the nicotinic acetylcholine receptors (nAChRs), a family of ligand-gated ion channels. When nicotine binds to nAChRs, the ligand-gated ion channels open and allow ions like calcium to enter the cell. Calcium can activate an assortment of downstream signaling processes, including further ionic currents via a calcium-gated ion channel (CaCC) called TMEM16A. Since this ion channel impacts neuron firing rate, we hypothesized that it may regulate the contribution of acetylcholine on cell firing. To test this, we used patch-clamp electrophysiology in acute slices of mouse brain and examined neuron firing rates in the medial habenula of the mice brains. Using Clampfit analysis, we were able to identify neuronal firing rates in these brain slices including changes elucidated by nAChR blockade. Here, we will present evidence that acetylcholine exhibits basal release into medial habenula neurons, and explain how TMEM16A feedback impacts resultant changes to neuron firing rates in nicotine-exposed animals.


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Apr 17th, 2:45 PM Apr 17th, 3:00 PM

The role of basal acetylcholine release on neuronal activity in the medial habenula

Nicotine is an addictive chemical that leads to tolerance and withdrawal and acts as an agonist for the nicotinic acetylcholine receptors (nAChRs), a family of ligand-gated ion channels. When nicotine binds to nAChRs, the ligand-gated ion channels open and allow ions like calcium to enter the cell. Calcium can activate an assortment of downstream signaling processes, including further ionic currents via a calcium-gated ion channel (CaCC) called TMEM16A. Since this ion channel impacts neuron firing rate, we hypothesized that it may regulate the contribution of acetylcholine on cell firing. To test this, we used patch-clamp electrophysiology in acute slices of mouse brain and examined neuron firing rates in the medial habenula of the mice brains. Using Clampfit analysis, we were able to identify neuronal firing rates in these brain slices including changes elucidated by nAChR blockade. Here, we will present evidence that acetylcholine exhibits basal release into medial habenula neurons, and explain how TMEM16A feedback impacts resultant changes to neuron firing rates in nicotine-exposed animals.