Optogenetic modulation of descending prefrontocortical inputs to the dorsal raphe bidirectionally bias socioaffective choices after social defeat.
Optogenetic modulation of descending prefrontocortical inputs to the dorsal raphe bidirectionally bias socioaffective choices after social defeat.
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DOI：
10.3389/fnbeh.2014.00043
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发表时间：
2014
影响因子：
3
通讯作者：
Berton O
中科院分区：
文献类型：
--
作者：
Challis C;Beck SG;Berton O
已经确定，调节人类和动物的5-羟色胺（5-HT）水平会影响对社会威胁的感知和反应，但在社会互动过程中控制5-HT输出的回路机制还不清楚。更好地了解这些系统可以为更精确和有效的治疗干预提供基础。在这里，我们研究了组织和可塑性的微电路牵连在中缝背核（DRN）的5-HT神经元的自上而下的控制兴奋性输入从腹内侧前额叶皮层（vmPFC）和他们的作用，在社会的接近回避的决定。我们在一个社会失败模型的背景下做了这件事，这个模型诱导了一种长期持续的社会厌恶，这种厌恶可以通过抗抑郁药逆转。我们首先使用病毒追踪和Cre依赖的遗传鉴定的VMPFC神经元突触的DRN，以确定其地形分布的关系，5-HT和GABA能亚区，发现兴奋性VMPFC的预测主要定位于GABA丰富的地区的DRN。然后，我们使用光遗传学结合cFos映射和切片电生理学来建立重复驱动DRN中的vmPFC输入的功能效应。我们提供了第一个直接的证据表明，vmPFC轴突驱动突触活动和立即早期基因表达的基因鉴定DRN GABA神经元通过AMPA受体依赖的机制。相比之下，我们没有检测到vmPFC驱动的突触活动在5-HT神经元和cFos诱导5-HT神经元是有限的。最后，我们表明，光遗传学增加或减少兴奋性vmPFC输入DRN在感觉暴露于侵略者的线索，增强或减少回避偏见，分别。这些结果阐明了vmPFC-DRN通路的功能组织，并确定GABA能神经元作为过滤自上而下的vmPFC对情感调节5-HT输出的影响的关键细胞元件。
It has been well established that modulating serotonin (5-HT) levels in humans and animals affects perception and response to social threats, however the circuit mechanisms that control 5-HT output during social interaction are not well understood. A better understanding of these systems could provide groundwork for more precise and efficient therapeutic interventions. Here we examined the organization and plasticity of microcircuits implicated in top-down control of 5-HT neurons in the dorsal raphe nucleus (DRN) by excitatory inputs from the ventromedial prefrontal cortex (vmPFC) and their role in social approach-avoidance decisions. We did this in the context of a social defeat model that induces a long lasting form of social aversion that is reversible by antidepressants. We first used viral tracing and Cre-dependent genetic identification of vmPFC glutamatergic synapses in the DRN to determine their topographic distribution in relation to 5-HT and GABAergic subregions and found that excitatory vmPFC projections primarily localized to GABA-rich areas of the DRN. We then used optogenetics in combination with cFos mapping and slice electrophysiology to establish the functional effects of repeatedly driving vmPFC inputs in DRN. We provide the first direct evidence that vmPFC axons drive synaptic activity and immediate early gene expression in genetically identified DRN GABA neurons through an AMPA receptor-dependent mechanism. In contrast, we did not detect vmPFC-driven synaptic activity in 5-HT neurons and cFos induction in 5-HT neurons was limited. Finally we show that optogenetically increasing or decreasing excitatory vmPFC input to the DRN during sensory exposure to an aggressor's cues enhances or diminishes avoidance bias, respectively. These results clarify the functional organization of vmPFC-DRN pathways and identify GABAergic neurons as a key cellular element filtering top-down vmPFC influences on affect-regulating 5-HT output.
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影响因子：
2
作者：
Derntl B;Seidel EM;Eickhoff SB;Kellermann T;Gur RC;Schneider F;Habel U
通讯作者：
Habel U
DOI：
10.1073/pnas.1301213110
发表时间：
2013-06-18
影响因子：
11.1
作者：
Chang, Steve W. C.;Brent, Lauren J. N.;Platt, Michael L.
通讯作者：
Platt, Michael L.
影响因子：
4.1
作者：
DEAKIN J F W;GRAEFF F G
通讯作者：
GRAEFF F G
DOI：
10.1111/j.1460-9568.2011.07936.x
发表时间：
2012-01
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Bang SJ;Jensen P;Dymecki SM;Commons KG
通讯作者：
Commons KG
影响因子：
5.3
作者：
Celada, P;Puig, MV;Artigas, F
通讯作者：
Artigas, F