Disinhibition-assisted long-term potentiation in the prefrontal-amygdala pathway via suppression of somatostatin-expressing interneurons.

Disinhibition-assisted long-term potentiation in the prefrontal-amygdala pathway via suppression of somatostatin-expressing interneurons.
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DOI:
10.1117/1.nph.7.1.015007
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发表时间:
2020-01-01
期刊:
影响因子:
5.3
通讯作者:
Morozov, Alexei
Morozov, Alexei
中科院分区:
医学2区
文献类型:
--
作者:
Ito, Wataru;Fusco, Brendon;Morozov, Alexei

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意义:自然的大脑适应通常涉及突触强度的变化。人工操作可以帮助研究突触强度在特定脑回路中的作用,不仅可以研究突触强度在相关神经元放电和振荡等各种生理现象中的作用,还可以研究突触强度在行为中的作用。突触前部位的高频和低频刺激已被广泛用于诱导长期增强(LTP)和抑郁。这种方法在许多脑区有效,但在基底外侧杏仁核(BLA)无效,因为BLA内强大的局部gaba能张力限制了突触的可塑性。目的:我们的目的是确定gaba能神经元的亚类,在从背内侧前额叶皮层(dmPFC)的BLA传入事件中调控LTP。方法:结合BLA传入神经的高频刺激,对BLA中特定gaba能神经元进行化学或光遗传抑制,作为LTP诱导的方法。结果:化学发生抑制生长抑素阳性中间神经元(Sst-INs)通过高频刺激传入神经使离体LTP发生,而抑制细小蛋白阳性中间神经元(PV-INs)则没有作用。此外,Arch光遗传学抑制Sst-INs也能使dmPFC-BLA突触在体内和体外发生LTP。结论:这些发现揭示了Sst-INs而非PV-INs在dmPFC-BLA通路中调控LTP,为BLA的人工突触促进提供了一种方法。
Significance: Natural brain adaptations often involve changes in synaptic strength. The artificial manipulations can help investigate the role of synaptic strength in a specific brain circuit not only in various physiological phenomena like correlated neuronal firing and oscillations but also in behaviors. High- and low-frequency stimulation at presynaptic sites has been used widely to induce long-term potentiation (LTP) and depression. This approach is effective in many brain areas but not in the basolateral amygdala (BLA) because the robust local GABAergic tone inside BLA restricts synaptic plasticity. Aim: We aimed at identifying the subclass of GABAergic neurons that gate LTP in the BLA afferents from the dorsomedial prefrontal cortex (dmPFC). Approach: Chemogenetic or optogenetic suppression of specific GABAergic neurons in BLA was combined with high-frequency stimulation of the BLA afferents as a method for LTP induction. Results: Chemogenetic suppression of somatostatin-positive interneurons (Sst-INs) enabled the ex vivo LTP by high-frequency stimulation of the afferent but the suppression of parvalbumin-positive interneurons (PV-INs) did not. Moreover, optogenetic suppression of Sst-INs with Arch also enabled LTP of the dmPFC-BLA synapses, both ex vivo and in vivo. Conclusions: These findings reveal that Sst-INs but not PV-INs gate LTP in the dmPFC-BLA pathway and provide a method for artificial synaptic facilitation in BLA.