Two opposing hippocampus to prefrontal cortex pathways for the control of approach and avoidance behavior

Abstract

The decision to either approach or avoid a potentially threatening environment is thought to rely upon complex connectivity between heterogenous neural populations in the ventral hippocampus and prefrontal cortex (PFC). However, how this circuitry can flexibly promote both approach or avoidance at different times has remained elusive. Here, we show that the projection to PFC is composed of two parallel circuits located in the superficial or deep hippocampal pyramidal layers. These circuits have unique upstream and downstream connectivity, and are differentially active during approach and avoidance behavior. The superficial population is preferentially connected to widespread PFC inhibitory interneurons, and its activation promotes exploration; while the deep circuit is connected to PFC pyramidal neurons and fast spiking interneurons, and its activation promotes avoidance. Together this provides a mechanism for regulation of behavior during approach avoidance conflict: through two specialized, parallel circuits that allow bidirectional hippocampal control of PFC.