Aberrations in basic sensory cortical processing are present in several neuropsychiatric disorders. Electrophysiological biomarkers of sensory processing dysfunction can be reliably measured in both human patients and animal models, providing a translational strategy for linking molecular, circuit, and cognitive aspects of the disease. We recently developed a mouse model with a mutation in the Kalrn gene observed in a cohort of individuals with schizophrenia. These Kalrn-PT mice recapitulate structural changes in patients with schizophrenia, including adolescent-onset dendritic changes in the neocortex. Here we sought to understand how these structural changes may affect neural synchrony in local and interregional cortical circuits, focusing on a sensory processing paradigm with established disease relevance.
We recorded dual local field potentials (LFPs) from primary visual cortex (V1) and anterior cingulate area (ACA) in awake mice during a visual oddball sequence, a clinically-relevant sensory stimulation paradigm used to quantify “mismatch negativity.” Adult male and female mice (P84-140) were used; we recorded from homozygous Kalrn-PT mutants (n=7) and their wildtype littermate controls (WT; n=7).
In V1, the Kalrn-PT mice exhibited diminished stimulus-induced broadband gamma power (Glass’s Δ = 0.621) and altered context-dependent gamma power responses (Glass’s Δ = 0.634), suggesting a disrupted “mismatch negativity” producing circuitry. Further, interregional phase synchrony between ACa and V1 was decreased in Kalrn-PT mice during the oddball paradigm, particularly in the theta-alpha band.
These results suggest that Kalrn-PT mutations likely affect inter-regional circuitry which underlies contextual processing of sensory information, potentially by impacting dendrite-targeted long-range inputs and inhibition via SST+ interneurons.
NIMH (R00MH115082); Whitehall Foundation; GSU Center for Neuroinflammation and Cardiometabolic Diseases
Schizophrenia, Mismatch Negativity, Mouse Model, Local Field Potentials, Visual Processing
© 2022 Published by Elsevier Inc.