Heterosynaptic interactions between dorsal and ventral hippocampus in individual medium spiny neurons of the nucleus accumbens ventromedial shell
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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) is a key connection involved in integrating environmental information and reward processing to facilitate 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, which led 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 adult male and female mice, we investigated anatomical and functional convergence of dHipp and vHipp in the NAc. We identified a subpopulation of dually innervated cells in the NAc medial shell where dHipp and vHipp inputs are located near one another along dendritic branches. We independently manipulated dHipp and vHipp inputs via two-color optogenetic manipulation during whole-cell electrophysiology recordings to confirm functional dual innervation of individual neurons and revealed heterosynaptic interactions between the two pathways. Altogether, these results demonstrate that dHipp and vHipp dually innervate a subset of neurons in the NAc, suggesting integration of these inputs at the level of individual neurons. 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 STATEMENT
Forming 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.
