Scaling of Ventral Hippocampal Activity during Anxiety.

Abstract

The hippocampus supports a multiplicity of functions, with the dorsal region contributing to spatial representations and memory and the ventral hippocampus (vH) being primarily involved in emotional processing. While spatial encoding has been extensively investigated, how the vH activity is tuned to emotional states, e.g., to different anxiety levels, is not well understood. We developed an adjustable linear track maze for male mice with which we could induce a scaling of behavioral anxiety levels within the same spatial environment. Using in vivo single-unit recordings, optogenetic manipulations, and population-level analysis, we examined the changes and causal effects of vH activity at different anxiety levels. We found that anxiogenic experiences activated the vH and that this activity scaled with increasing anxiety levels. We identified two processes that contributed to this scaling of anxiety-related activity: increased tuning and successive remapping of neurons to the anxiogenic compartment. Moreover, optogenetic inhibition of the vH reduced anxiety across different levels, while anxiety-related activity scaling could be decoded using a linear classifier. Collectively, our findings position the vH as a critical limbic region that functions as an "anxiometer" by scaling its activity based on perceived anxiety levels. Our discoveries go beyond the traditional theory of cognitive maps in the hippocampus underlying spatial navigation and memory, by identifying hippocampal mechanisms selectively regulating anxiety.