P489. Cell-Type and Frequency-Specific Circuit for Mismatch Negativity in Mice


      Processing sensory information in line with concurrent context is disrupted in schizophrenia. Mismatch negativity (MMN) is an EEG event related potential that indexes how early sensory cortical responses differ to contextually unexpected events. Importantly, reduced auditory and visual MMN is a biomarker of schizophrenia. Despite this disease relevance, a circuit-level understanding of MMN generation is missing. Our past work in mouse visual cortex (V1) shows that the generation of a rodent analogue of MMN relies on both local interneurons and feedback input from higher areas of cortex. Here we sought to understand how such top-down and local circuitry interacts to process stimuli in context.


      We recorded local field potentials from anterior cingulate area (ACa) and V1 in awake mice during a visual oddball paradigm to quantify ACa-V1 synchrony in different oscillatory frequency bands. We then tested the cell-level mediators of this synchrony using opto- and chemo-genetics to activate or suppress ACa axonal inputs to and different cell populations (VIP, SST, PYR) in V1.


      During the oddball paradigm, ACa and V1 showed strong coherence at the alpha band (6-10Hz, n=7). Two-photon quantification of calcium signals in V1 showed increased VIP activity when ACa inputs were driven at the alpha band, while SST cells were inhibited (n=12). Further, naturally occurring alpha-band coherence and MMN-like signals in the LFP was disrupted by chemicogenetic inhibition of VIP interneurons in V1 (n=7).


      The study elucidates cell- and frequency-specific circuitry which could be key to understand sensory disturbances in schizophrenia and point to more precise treatments.

      Supported By

      NIMH, Whitehall Foundation


      Circuits, Alpha Oscillation, Top-down Control, Mismatch Negativity, Schizophrenia