Rosen Zev B, Cheung Stephanie, Siegelbaum Steven A
Department of Neuroscience, Columbia University, New York, New York, USA.
Department of Pharmacology, Columbia University, New York, New York, USA.
Nat Neurosci. 2015 Dec;18(12):1763-71. doi: 10.1038/nn.4152. Epub 2015 Nov 2.
Dopamine (DA) is required for hippocampal-dependent memory and long-term potentiation (LTP) at CA1 Schaffer collateral (SC) synapses. It is therefore surprising that exogenously applied DA has little effect on SC synapses, but suppresses CA1 perforant path (PP) inputs. To examine DA actions under more physiological conditions, we used optogenetics to release DA from ventral tegmental area inputs to hippocampus. Unlike exogenous DA application, optogenetic release of DA caused a bidirectional, activity-dependent modulation of SC synapses, with no effect on PP inputs. Low levels of DA release, simulating tonic DA neuron firing, depressed the SC response through a D4 receptor-dependent enhancement of feedforward inhibition mediated by parvalbumin-expressing interneurons. Higher levels of DA release, simulating phasic firing, increased SC responses through a D1 receptor-dependent enhancement of excitatory transmission. Thus, tonic-phasic transitions in DA neuron firing in response to motivational demands may cause a modulatory switch from inhibition to enhancement of hippocampal information flow.
多巴胺（DA）对于海马体依赖的记忆以及CA1区谢弗侧支（SC）突触处的长时程增强（LTP）是必需的。因此，令人惊讶的是，外源性应用的DA对SC突触几乎没有影响，但会抑制CA1区穿通通路（PP）的输入。为了在更生理的条件下研究DA的作用，我们使用光遗传学从腹侧被盖区输入到海马体来释放DA。与外源性应用DA不同，光遗传学释放DA引起了SC突触的双向、活动依赖性调制，对PP输入没有影响。低水平的DA释放，模拟紧张性DA神经元放电，通过表达小白蛋白的中间神经元介导的前馈抑制的D4受体依赖性增强来抑制SC反应。更高水平的DA释放，模拟相位性放电，通过D1受体依赖性增强兴奋性传递来增加SC反应。因此，DA神经元放电中响应动机需求的紧张性-相位性转变可能导致从抑制到增强海马体信息流的调制开关。
