Meso-py: Dual brain cortical calcium imaging in mice during head-fixed social stimulus presentation

Abstract

We present a cost-effective, compact foot-print, and open source Raspberry Pi-based wide field imaging system. The compact nature allows the system to be used for close-proximity dual-brain cortical mesoscale functional-imaging to simultaneously observe activity in two head-fixed animals in a staged social touch-like interaction. We provide all schematics, code, and protocols for a rail system where head-fixed mice are brought together to a distance where the macrovibrissae of each mouse make contact. Cortical neuronal functional signals (GCaMP6s; genetically encoded Ca²⁺ sensor) were recorded from both mice simultaneously before, during, and after the social contact period. When the mice were together, we observed bouts of mutual whisking and cross-mouse correlated cortical activity across the cortex. Correlations were not observed in trial-shuffled mouse pairs, suggesting that correlated activity was specific to individual interactions. Whisking-related cortical signals were observed during the period where mice were together (closest contact). The effects of social stimulus presentation extend outside of regions associated with mutual touch and have global synchronizing effects on cortical activity.

Significance Statement

We developed a system to provide a staged encounter between two head-fixed mice, allowing for simultaneous imaging of behavior and wide-field dorsal cortical calcium activity in both animals throughout the encounter. In our experiments, neural signals between animals became more highly correlated during interaction periods, where physical touch between whiskers was possible. We also provide instructions and resources for investigators to develop standalone raspberry pi-based, mesoscale cortical calcium imaging systems. We anticipate that this method will provide a reproducible system to probe relationships between brain-to-brain activity during social interactions between mice.