Heterosynaptic interactions between dorsal and ventral hippocampus in individual medium spiny neurons of the nucleus accumbens ventromedial shell

Abstract

Establishing learned associations between rewarding stimuli and the context under which those rewards are encountered is critical for survival. Hippocampal input to the nucleus accumbens (NAc) provides important environmental context to reward processing to support goal-directed behaviors. This connection consists of two independent pathways originating from the dorsal (dHipp) or ventral (vHipp) hippocampus, which have previously been considered functionally and anatomically distinct. Here, we show overlap in dHipp and vHipp terminal fields in the NAc, leading us to reconsider this view and raise new questions regarding the potential interactions between dHipp and vHipp pathways in the NAc. Using optogenetics, electrophysiology, and transsynaptic labeling in mice, we investigated anatomical and functional convergence of dHipp and vHipp inputs in the NAc. Transsynaptic labeling revealed a subpopulation of dually innervated cells in the NAc medial shell, confirmed by independent optogenetic manipulation of dHipp and vHipp inputs during whole-cell electrophysiological recordings. Further analysis revealed closely apposed dHipp and vHipp inputs along dendritic branches, and simultaneous stimulation of both inputs elicited heterosynaptic potentiation. Comparison of observed and theoretical success rates suggests interactions between dHipp-NAc and vHipp-NAc synapses may occur presynaptically. Altogether, these results demonstrate that inputs originating from dHipp and vHipp converge onto a subset of NAc neurons with synapses positioned to enable rapid heterosynaptic interactions, indicating integration of these inputs at the single-neuron level. Exploring the physiological and behavioral implications of this convergence will offer new insights into how individual neurons incorporate information from distinct inputs and how this integration may shape learning. SIGNIFICANCE STATEMENTForming associations between rewards and the circumstances under which they are experienced is vital for survival. Hipp input to the NAc is essential for associating rewards with their environmental context to effectively guide motivated behaviors. This connection consists of two separate pathways originating from dHipp and vHipp that have long been considered distinct. Here, we reveal a subpopulation of neurons in the NAc shell innervated by both Hipp subregions as well as heterosynaptic interactions that occur between dHipp and vHipp synapses. These findings suggest that integration of distinct hippocampal information occurs at the single-neuron level, providing a critical mechanism underlying learning and motivated behavior while also opening new avenues for understanding how diverse contextual and reward signals shape decision-making.