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Related Experiment Video

Updated: Jun 6, 2026

Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices

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Published on: April 5, 2016

Striatal Cholinergic Interneurons Signal Aversion and Drive Avoidance.

Yuxin Zhou, Hua-An Tseng, Jiancheng Xie

Biorxiv : the Preprint Server for Biology

|June 5, 2026

Summary

Striatal cholinergic interneurons (ChIs) actively signal aversion. Silencing their excitation impairs avoidance learning, revealing a key cholinergic mechanism for negative outcome learning.

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Area of Science:

Neuroscience
Computational Neuroscience
Behavioral Neuroscience

Background:

Seeking reward and avoiding punishment are crucial for survival.
The neural mechanisms underlying aversive learning and avoidance behavior are not fully understood.
Striatal cholinergic interneurons (ChIs) are implicated in reinforcement learning but their specific role in aversion is unclear.

Purpose of the Study:

To investigate the role of striatal cholinergic interneurons (ChIs) in learning aversive value and generating avoidance behavior.
To determine if ChIs signal negative outcomes and contribute to conditioned avoidance.

Main Methods:

Voltage imaging in mice performing aversive and reward conditioning tasks.
Analysis of subthreshold membrane voltage and suprathreshold spiking of individual ChIs.
Optogenetic silencing of ChI excitation during behavioral tasks.

Main Results:

ChIs showed stronger excitation to cues predicting negative outcomes compared to positive outcomes.
This valence-dependent response augmentation was linked to learning about negative outcomes.
Optogenetic silencing of ChI excitation selectively impaired conditioned avoidance, but not conditioned approach.

Conclusions:

Striatal cholinergic interneurons (ChIs) actively signal evidence for aversion.
ChIs play a critical role in driving conditioned avoidance behavior.
These findings highlight a novel cholinergic mechanism underlying aversive learning.