Decoding auditory cognition: Unraveling the corticostriatal-SNr circuit's role in frequency discrimination accuracy

  • iScience. 2025 Nov 22;28(12):114184. doi: 10.1016/j.isci.2025.114184.
Zhao-Qun Wang  1 ,  Peng-Hui Chen  1 ,  Hui-Zhong Wen  1 ,  Tian-Tian Luo  1 ,  Yun-Xiao Lou  1 ,  Yan-Dong Zhao  1 ,  Tong Zhu  2 ,  Guang-Yan Wu  2 ,  Ying Xiong  1
Affiliations
  • 1. Department of Neurobiology, College of Basic Medicine, Army Medical University, Chongqing 400038, China.
  • 2. Breast and Thyroid Surgery, The First Affiliated Hospital of Army Medical University, Chongqing 400038, China.
PMID: 41438078 DOI: 10.1016/j.isci.2025.114184
Abstract

The anterior auditory field (AAF) is critical for auditory discrimination, though underlying neural pathways remain unclear. Using viral tracing, optogenetics/pharmacogenetics, and behavior, we investigated the corticostriatal-substantia nigra pars reticulata (SNr) circuit's role in frequency discrimination. AAF excitatory neurons, synapsing on caudate putamen (CPu) GABAergic neurons, were highly active during tasks. Pharmacogenetic suppression of AAF→CPuGABA projections impaired discrimination performance. We further identified an AAF→CPu D1-medium spiny neuron (MSN) pathway regulating discrimination; its pharmacogenetic/optogenetic inhibition caused deficits. Histology confirmed CPuD1→SNr projections. Critically, suppressing/ablating AAF→CPu→SNr circuit neurons severely disrupted accuracy. Fiber photometry revealed SNrGABA neuron activation during tasks. Together, AAF→CPuD1 projections and the AAF→CPu→SNr circuit are pivotal for frequency discrimination, advancing mechanistic insights into auditory processing circuits.

Keywords
Cognitive neuroscience; Sensory neuroscience.
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