Voltage imaging of CA1 pyramidal cells and SST+ interneurons reveals stability and plasticity mechanisms of spatial firing

Abstract Hippocampal place cells (PCs) are important for spatial coding and episodic memory. PCs’ representations are modulated upon transitioning between environments (global remapping) but also change with repeated exposure to familiar spaces (representational drift). To gain insights into the mechanistic basis for this unique balance between circuit plasticity and stability, we used voltage imaging to longitudinally record the subthreshold and spiking activity of pyramidal neurons (PNs) and somatostatin-positive (SST) interneurons in CA1 during virtual navigation. A fraction of cells from both populations showed spatial representations, but many SSTs were speed-tuned or fired uniformly across space. Intracellular recordings revealed increased theta power and asymmetric ramp-like depolarization in PN place fields, while SSTs exhibited symmetric depolarization with no theta increase. Longitudinal recordings across weeks demonstrated representational drifts in both populations, although SSTs exhibited remarkably stable firing and subthreshold properties. Transition to a novel environment induced remapping in both populations, accompanied by increase in SST activity and reduction in PNs. These results provide new insights into how hippocampal circuits balance representational stability with experience-dependent plasticity.