Department of Psychology, University of Washington, Washington, USA.
Hippocampus. 2011 Feb;21(2):172-84. doi: 10.1002/hipo.20734.
Hippocampus (HPC) receives dopaminergic (DA) projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences HPC dependent behaviors and place fields. We examined how efferent projections from VTA to HPC influence spatial working memory and place fields when the reward context changes. CA1 and CA3 process environmental context changes differently and VTA preferentially innervates CA1. Given these anatomical data and electrophysiological evidence that implicate DA in reward processing, we predicted that CA1 place fields would respond more strongly to both VTA disruption and changes in the reward context than CA3 place fields. Rats (N = 9) were implanted with infusion cannula targeting VTA and recording tetrodes aimed at HPC. Then they were tested on a differential reward, win-shift working memory task. One recording session consisted of 5 baseline and 5 manipulation trials during which place cells in CA1/CA2 (N = 167) and CA3 (N = 94) were recorded. Prior to manipulation trials rats were infused with either baclofen or saline and then subjected to control or reward conditions during which the learned locations of large and small reward quantities were reversed. VTA disruption resulted in an increase in errors, and in CA1/CA2 place field reorganization. There were no changes in any measures of CA3 place field stability during VTA disruption. Reward manipulations did not affect performance or place field stability in CA1/CA2 or CA3; however, changes in the reward locations "rescued" performance and place field stability in CA1/CA2 when VTA activity was compromised, perhaps by trigging compensatory mechanisms. These data support the hypothesis that VTA contributes to spatial working memory performance perhaps by maintaining place field stability selectively in CA1/CA2.
海马体(HPC)接收来自腹侧被盖区(VTA)和黑质的多巴胺能(DA)投射。这些输入似乎提供了一种调制信号,影响依赖 HPC 的行为和位置场。我们研究了当奖励环境发生变化时,来自 VTA 的传出投射如何影响空间工作记忆和位置场。CA1 和 CA3 以不同的方式处理环境上下文变化,而 VTA 优先支配 CA1。鉴于这些解剖学数据和涉及 DA 在奖励处理中的电生理证据,我们预测 CA1 位置场对 VTA 破坏和奖励环境变化的反应会比 CA3 位置场更强。大鼠(N=9)植入了针对 VTA 的输注套管和针对 HPC 的记录四极管。然后,他们在差异奖励、赢移工作记忆任务上进行了测试。一个记录会议由 5 个基线和 5 个操作试验组成,在此期间记录了 CA1/CA2(N=167)和 CA3(N=94)中的位置细胞。在操作试验之前,大鼠被注入巴氯芬或生理盐水,然后在控制或奖励条件下进行试验,在此期间,大、小奖励量的学习位置被颠倒。VTA 破坏导致错误增加和 CA1/CA2 位置场重组。在 VTA 破坏期间,CA3 位置场稳定性的任何测量值都没有变化。奖励操作不影响 CA1/CA2 或 CA3 的表现或位置场稳定性;然而,当 VTA 活动受损时,奖励位置的变化“挽救”了 CA1/CA2 的表现和位置场稳定性,也许是通过触发补偿机制。这些数据支持 VTA 有助于空间工作记忆表现的假设,也许是通过选择性地维持 CA1/CA2 中的位置场稳定性。