Optogenetic Study of Anterior BNST and Basomedial Amygdala Projections to the Ventromedial Hypothalamus.
Optogenetic Study of Anterior BNST and Basomedial Amygdala Projections to the Ventromedial Hypothalamus.
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DOI：
10.1523/eneuro.0204-18.2018
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发表时间：
2018-05
期刊：
影响因子：
3.4
通讯作者：
Pare D
中科院分区：
文献类型：
--
作者：
Yamamoto R;Ahmed N;Ito T;Gungor NZ;Pare D
杏仁基底内侧核(BM)通过谷氨酸能直接投射和通过终纹床核前部(BNSTa)间接影响下丘脑腹内侧核(VMH)。然而，在VMH中，BM和BNSTa轴突以分离的方式结束。BM投射到VMH的核心，VMH的投射细胞位于VMH的核心，而BNSTa投射到VMH的外壳，那里集中了抑制核心神经元的GABA能细胞。然而，BM和BNSTa对VMH的这种双重监管的后果尚不清楚。为了研究这个问题，我们在转基因小鼠中记录了VMH的外壳和核心神经元对BM或BNSTa输入的光遗传激活的反应，转基因小鼠选择性地在谷氨酸或GABA能神经元中表达Cre重组酶。谷氨酸BM能激发大多数核心神经元，但不能引起GABA能壳层神经元的反应。在Vgat-res-Cre-Ai6小鼠骨髓内注入AAv-EF1α-DIo-hChR2-mCherry后，在VMH内未观察到顺行标记，提示GABA能的BM神经元不投射到VMH。相比之下，BNSTa主要发送GABA能投射，既抑制外壳神经元，也抑制核心神经元。然而，BNSTa诱发的IPSP在壳层神经元中具有更高的幅度。由于我们还发现GABA能壳神经元的激活会导致核心神经元的抑制，这些结果表明，根据壳神经元的放电频率，BNSTa的输入可以引起核心神经元的净抑制或去抑制。因此，BM和BNSTa对VMH的双重监管为这种防御和社会行为的监管提供了灵活性。
The basomedial amygdala (BM) influences the ventromedial nucleus of the hypothalamus (VMH) through direct glutamatergic projections as well as indirectly, through the anterior part of the bed nucleus of the stria terminalis (BNSTa). However, BM and BNSTa axons end in a segregated fashion in VMH. BM projects to the core of VMH, where VMH’s projection cells are located, whereas BNSTa projects to the shell of VMH, where GABAergic cells that inhibit core neurons are concentrated. However, the consequences of this dual regulation of VMH by BM and BNSTa are unknown. To study this question, we recorded the responses of VMH’s shell and core neurons to the optogenetic activation of BM or BNSTa inputs in transgenic mice that selectively express Cre-recombinase in glutamatergic or GABAergic neurons. Glutamatergic BM inputs fired most core neurons but elicited no response in GABAergic shell neurons. Following BM infusions of AAV-EF1α-DIO-hChR2-mCherry in Vgat-ires-Cre-Ai6 mice, no anterograde labeling was observed in the VMH, suggesting that GABAergic BM neurons do not project to the VMH. In contrast, BNSTa sent mostly GABAergic projections that inhibited both shell and core neurons. However, BNSTa-evoked IPSPs had a higher amplitude in shell neurons. Since we also found that activation of GABAergic shell neurons causes an inhibition of core neurons, these results suggest that depending on the firing rate of shell neurons, BNSTa inputs could elicit a net inhibition or disinhibition of core neurons. Thus, the dual regulation of VMH by BM and BNSTa imparts flexibility to this regulator of defensive and social behaviors.