Stanley Adrien, Choi Se Joon, Frank Anika, Makowicz Emily, Cataldi Stefano, N Shashaank, Mosharov Eugene V, Lacefield Clay, Miniaci Maria Concetta, Sulzer David
Department of Biological Sciences, Columbia University, New York State Psychiatric Institute, New York, NY 10032.
Departments of Psychiatry, Columbia University: Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032.
bioRxiv. 2025 May 19:2025.04.29.651089. doi: 10.1101/2025.04.29.651089.
The association of a sensory cue with an outcome is a crucial step in learning to identify safe versus threatening situations. Here we assessed how learned sound-safety association alters neuronal activity in tail of the striatum (TS), where auditory cortical and thalamic inputs converge. Prior to training, foot shock elicited responses by TS direct and indirect pathway spiny projection neurons (SPNs), while sound tones produced no response. However, once the sound association was learned, sound tones strongly activated TS SPNs, even when the animal was under anesthesia. This conditioned auditory response occurred concurrently with alterations of direct pathway SPNs in the TS, including increased responses to cortical and auditory thalamic inputs, increased excitatory response with an enhanced ratio of NMDA to AMPA receptors, decreased responses to inhibitory input, and increased dendritic spines. This convergence of postsynaptic changes provides responses to relevant auditory cues during associative learning.
将感觉线索与结果联系起来是学习识别安全与威胁情境的关键一步。在此，我们评估了习得的声音 - 安全关联如何改变纹状体尾部（TS）的神经元活动，听觉皮层和丘脑输入在此汇聚。在训练前，足部电击会引发TS直接和间接通路棘状投射神经元（SPN）的反应，而纯音则无反应。然而，一旦学会声音关联，即使动物处于麻醉状态，纯音也会强烈激活TS SPN。这种条件性听觉反应与TS中直接通路SPN的变化同时发生，包括对皮层和听觉丘脑输入的反应增加、NMDA与AMPA受体比例增加导致兴奋性反应增强、对抑制性输入的反应减少以及树突棘增加。突触后变化的这种汇聚在联想学习过程中提供了对相关听觉线索的反应。
