1. Academic Validation
  2. A hippocampus dependent neural circuit loop underlying the generation of auditory mismatch negativity

A hippocampus dependent neural circuit loop underlying the generation of auditory mismatch negativity

  • Neuropharmacology. 2022 Mar 15;206:108947. doi: 10.1016/j.neuropharm.2022.108947.
Guo-Liang Yi 1 Min-Zhen Zhu 1 He-Chen Cui 1 Xin-Rui Yuan 1 Peng Liu 1 Jie Tang 1 Yuan-Qing Li 2 Xin-Hong Zhu 3
Affiliations

Affiliations

  • 1 Institute of Mental Health, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 2 Research Center for Brain-Computer Interface, Pazhou Lab, Guangzhou, 510330, China.
  • 3 Institute of Mental Health, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China; Research Center for Brain Health, Pazhou Lab, Guangzhou, 510330, China; School of Psychology, Shenzhen University, Shenzhen, 518060, China. Electronic address: zhuxh527@126.com.
Abstract

Extracting relevant information and transforming it into appropriate behavior, is a fundamental brain function, and requires the coordination between the sensory and cognitive systems, however, the underlying mechanisms of interplay between sensory and cognition systems remain largely unknown. Here, we developed a mouse model for mimicking human auditory mismatch negativity (MMN), a well-characterized translational biomarker for schizophrenia, and an index of early auditory information processing. We found that a subanesthetic dose of ketamine decreased the amplitude of MMN in adult mice. Using pharmacological and chemogenetic approaches, we identified an auditory cortex-entorhinal cortex-hippocampus neural circuit loop that is required for the generation of MMN. In addition, we found that inhibition of dCA1→MEC circuit impaired the auditory related fear discrimination. Moreover, we found that ketamine induced MMN deficiency by inhibition of long-range GABAergic projection from the CA1 region of the dorsal hippocampus to the medial entorhinal cortex. These results provided circuit insights for ketamine effects and early auditory information processing. As the entorhinal cortex is the interface between the neocortex and hippocampus, and the hippocampus is critical for the formation, consolidation, and retrieval of episodic memories and other cognition, our results provide a neural mechanism for the interplay between the sensory and cognition systems.

Keywords

Early auditory information processing (EAP); Hippocampus; Ketamine; Medial entorhinal cortex (MEC); Mismatch negativity (MMN); γ-aminobutyric acid (GABA).

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