Heterosynaptic GABAB Receptor Function within Feedforward Microcircuits Gates Glutamatergic Transmission in the Nucleus Accumbens Core
Heterosynaptic GABAB Receptor Function within Feedforward Microcircuits Gates Glutamatergic Transmission in the Nucleus Accumbens Core
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DOI：
10.1523/jneurosci.1395-19.2019
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发表时间：
2019-11-20
影响因子：
5.3
通讯作者：
Grueter, Brad A.
中科院分区：
文献类型：
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作者：
Manz, Kevin M.;Baxley, Andrew G.;Grueter, Brad A.
丘脑核（NAc）内复杂的回路相互作用促进目标导向行为。中型多刺神经元（MSN）介导NAc输出投射到功能不同的大脑区域，赋予的属性，部分，由D1和D2多巴胺受体表达MSN的差异投射模式。NAc的谷氨酸能传入通过募集由表达小白蛋白（PV）的中间神经元（IN）组成的前馈抑制微回路来指导MSN输出。此外，GABA（B）异源受体（GABA（B）R），一种G（i/o）-偶联的G-蛋白偶联受体，在整个中脑边缘网络的突触能突触处表达，但其在NAc内的生理背景和突触机制仍然未知。在这里，我们探讨了GABA（B）R的功能，在多巴胺能突触内PV-IN嵌入的微电路在NAC核心的雄性小鼠。我们发现，GABA（B）R在突触前表达，并募集非经典信号传导机制，以降低D1（+）和D1（-）（推定的D2）MSN亚型的多巴胺能突触效能。此外，PV-IN是NAc中神经元GABA的强大来源，异突触靶向GABA（B）R以选择性地调节D1（+）MSN上的多巴胺能传递。这些发现阐明了前馈抑制的一种新机制，并完善了GABA（B）异源受体调节中脑边缘回路功能的机制。
Complex circuit interactions within the nucleus accumbens (NAc) facilitate goal-directed behavior. Medium spiny neurons (MSNs) mediate NAc output by projecting to functionally divergent brain regions, a property conferred, in part, by the differential projection patterns of D1- and D2 dopamine receptor-expressing MSNs. Glutamatergic afferents to the NAc direct MSN output by recruiting feedforward inhibitory microcircuits comprised of parvalbumin (PV)-expressing interneurons (INs). Furthermore, the GABA(B) heteroreceptor (GABA(B)R), a G(i/o) -coupled G-protein-coupled receptor, is expressed at glutamatergic synapses throughout the mesolimbic network, yet its physiological context and synaptic mechanism within the NAc remains unknown. Here, we explored GABA(B)R function at glutamatergic synapses within PV-IN-embedded microcircuits in the NAc core of male mice. We found that GABA(B)R is expressed presynaptically and recruits a noncanonical signaling mechanism to reduce glutamatergic synaptic efficacy at D1 (+) and D1 (-) (putative D2) MSN subtypes. Furthermore, PV-INs, a robust source of neuronal GABA in the NAc, heterosynaptically target GABA(B)R to selectively modulate glutamatergic transmission onto D1 (+) MSNs. These fmdings elucidate a new mechanism of feedforward inhibition and refine mechanisms by which GABA(B) heteroreceptors modulate mesolimbic circuit function.