Biased connectivity of brain-wide inputs to ventral subiculum output neurons

Abstract

The ventral subiculum (vS) of the mouse hippocampus coordinates diverse behaviours through heterogeneous populations of projection neurons. These neurons transmit signals to multiple brain regions by integrating thousands of local and long-range synaptic inputs. However, whether each population is selectively innervated by different afferent input remains unknown. To address this question, we employed projection-specific rabies tracing to study the input-output relationship of vS output neurons. Analysis of brain-wide inputs reveals quantitative input differences that can be explained by the spatial location of postsynaptic neurons along the proximal-distal axis of vS and the identity of the downstream target. Further, the input from nucleus reuniens, an area thought to underlie vS and prefrontal cortex (PFC) reciprocal connectivity, is unexpectedly biased away from PFC-projecting vS neurons. Overall, we reveal prominent heterogeneity in brain-wide inputs to the vS parallel output circuitry, providing a basis for the selective control of individual projections during behaviour.