Scaling of ventral hippocampal activity during anxiety

Abstract

BackgroundThe hippocampus supports a multiplicity of functions, with the dorsal region contributing to memory-related spatial representations, while the ventral hippocampus (vH) is 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.MethodsWe developed an adjustable linear track maze (aLTM) for mice to induce different anxiety levels within the same spatial environment. Throughin vivosingle-unit recordings, optogenetic manipulations, and the application of a convolutional classifier, we examined the changes and causal effects of vH activity at different anxiety levels.ResultsWe found that anxiogenic experiences activated the vH and that this activity scaled with increasing anxiety levels within the same spatial environment. We identified two processes that contributed to this scaling of anxiety-related activity: rate remapping and the successive recruitment of neurons. Moreover, optogenetic inhibition of the vH reduced anxiety across different levels, while anxiety-related activity scaling could be decoded using a convolutional classifier.ConclusionsOur 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.