Copenhaver Ashley E, Vance Sydnee, Snider Sarah A, Befano Kaela, LeGates Tara A
Department of Biological Sciences, University of Maryland, Baltimore County (UMBC).
Department of Physiology and Pharmacology, University of Maryland School of Medicine.
bioRxiv. 2025 Jun 23:2025.06.23.661109. doi: 10.1101/2025.06.23.661109.
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.
在奖励刺激与获得这些奖励的环境之间建立习得性关联对生存至关重要。海马体向伏隔核（NAc）的输入是一个关键连接，参与整合环境信息和奖励处理，以促进目标导向行为。这种连接由源自背侧（dHipp）或腹侧（vHipp）海马体的两条独立通路组成，此前一直被认为在功能和解剖学上是不同的。在这里，我们展示了伏隔核中背侧海马体和腹侧海马体终末场的重叠，这使我们重新审视这一观点，并对背侧海马体和腹侧海马体通路在伏隔核中的潜在相互作用提出了新问题。利用成年雄性和雌性小鼠的光遗传学、电生理学和跨突触标记技术，我们研究了背侧海马体和腹侧海马体在伏隔核中的解剖学和功能汇聚。我们在伏隔核内侧壳中鉴定出一个双神经支配细胞亚群，其中背侧海马体和腹侧海马体输入沿着树突分支彼此靠近。在全细胞膜片钳电生理记录过程中，我们通过双色光遗传学操作独立操纵背侧海马体和腹侧海马体输入，以确认单个神经元的功能双神经支配，并揭示了两条通路之间的异突触相互作用。总之，这些结果表明背侧海马体和腹侧海马体双神经支配伏隔核中的一部分神经元，提示这些输入在单个神经元水平上的整合。探索这种汇聚的生理和行为学意义将为单个神经元如何整合来自不同输入的信息以及这种整合如何塑造学习提供新的见解。
