Electrophysiological signatures of visual recognition memory across all layers of mouse V1

Abstract

In mouse primary visual cortex (V1), familiar stimuli evoke significantly altered responses when compared to novel stimuli. This stimulus-selective response plasticity (SRP) was described originally as an increase in the magnitude of visual evoked potentials (VEPs) elicited in layer 4 (L4) by familiar phase-reversing grating stimuli. SRP is dependent on NMDA receptors (NMDAR) and has been hypothesized to reflect potentiation of thalamocortical synapses in L4. However, recent evidence indicates that the synaptic modifications that manifest as SRP do not occur on L4 principal cells. To shed light on where and how SRP is induced and expressed in male and female mice, the present study had three related aims: (1) to confirm that NMDAR are required specifically in glutamatergic principal neurons of V1, (2) to investigate the consequences of deleting NMDAR specifically in L6, and (3) to use translaminar electrophysiological recordings to characterize SRP expression in different layers of V1. We find that knockout of NMDAR in L6 principal neurons disrupts SRP. Current-source density analysis of the VEP depth profile shows augmentation of short latency current sinks in layers 3, 4 and 6 in response to phase reversals of familiar stimuli. Multiunit recordings demonstrate that increased peak firing occurs in response to phase reversals of familiar stimuli across all layers, but that activity between phase reversals is suppressed. Together, these data reveal important aspects of the underlying phenomenology of SRP and generate new hypotheses for the expression of experience-dependent plasticity in V1.

Significance Statement

Repeated exposure to stimuli that portend neither reward nor punishment leads to behavioral habituation, enabling organisms to dedicate attention to novel or otherwise significant features of the environment. The neural basis of this process, which is so often dysregulated in neurological and psychiatric disorders, remains poorly understood. Learning and memory of stimulus familiarity can be studied in mouse visual cortex by measuring electrophysiological responses to simple phase-reversing grating stimuli. The current study advances knowledge of this process by documenting changes in visual evoked potentials, neuronal spiking activity, and oscillations in the local field potentials across all layers of mouse visual cortex. In addition, we identify a key contribution of a specific population of neurons in layer 6 of visual cortex.