Monosynaptic inputs to ventral tegmental area glutamate and GABA co-transmitting neurons.
Monosynaptic inputs to ventral tegmental area glutamate and GABA co-transmitting neurons.
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腹侧被盖区谷氨酸和 GABA 共传递神经元的单突触输入。
DOI：
10.1101/2023.04.06.535959
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Root,Dav
中科院分区：
文献类型：
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作者：
Prévost,EmilyD;Phillips,Alysabeth;Lauridsen,Kristoffer;Enserro,Gunnar;Rubinstein,Bodhi;Alas,Daniel;McGovern,DillonJ;Ly,Annie;Banks,Makaila;McNulty,Connor;Kim,YoonSeok;Fenno,LiefE;Ramakrishnan,Charu;Deisseroth,Karl;Root,Dav
腹侧被盖区（VTA）神经元的独特群体共同传递谷氨酸和GABA。然而，VTA VGluT2+VGaT+神经元的电路输入是未知的，限制了我们对其功能能力的理解。通过将单突触狂犬病追踪与交叉基因靶向结合在雄性和雌性小鼠中，我们发现VTA VGluT2+VGaT+神经元接受不同的全脑输入。对VTA VGluT2+VGaT+神经元的单突触输入最多的是上丘（SC）、外侧下丘脑（LH）、中脑网状核和导水管周围灰质，而相对于脑区体积而言，最密集的输入来自中缝背核、外侧束和VTA。基于这些和先前的数据，我们假设LH和SC输入来自谷氨酸能神经元。无论刺激频率如何，光激活谷氨酸能LH神经元激活VTA VGluT2+VGaT+神经元，导致类似逃跑的移动行为。相比之下，谷氨酸能SC神经元的光学激活在短时间内以高频率激活VTA VGluT2+VGaT+神经元，导致头部旋转和移动行为受阻（冻结）。刺激谷氨酸能LH神经元，而不是谷氨酸能SC神经元，与VTA VGluT2+VGaT+足震诱导的活性相关，抑制LH谷氨酸能神经元会破坏VTA VGluT2+VGaT+尾震诱导的活性。我们对这些结果的解释是，VTA VGluT2+VGaT+神经元的输入可能整合了与动机显著性结果的检测和处理相关的各种信号。
A unique population of ventral tegmental area (VTA) neurons co-transmits glutamate and GABA. However, the circuit inputs to VTA VGluT2+VGaT+ neurons are unknown, limiting our understanding of their functional capabilities. By coupling monosynaptic rabies tracing with intersectional genetic targeting in male and female mice, we found that VTA VGluT2+VGaT+ neurons received diverse brainwide inputs. The largest numbers of monosynaptic inputs to VTA VGluT2+VGaT+ neurons were from superior colliculus (SC), lateral hypothalamus (LH), midbrain reticular nucleus, and periaqueductal gray, whereas the densest inputs relative to brain region volume were from the dorsal raphe nucleus, lateral habenula, and VTA. Based on these and prior data, we hypothesized that LH and SC inputs were from glutamatergic neurons. Optical activation of glutamatergic LH neurons activated VTA VGluT2+VGaT+ neurons regardless of stimulation frequency and resulted in flee-like ambulatory behavior. In contrast, optical activation of glutamatergic SC neurons activated VTA VGluT2+VGaT+ neurons for a brief period of time at high frequency and resulted in head rotation and arrested ambulatory behavior (freezing). Stimulation of glutamatergic LH neurons, but not glutamatergic SC neurons, was associated with VTA VGluT2+VGaT+ footshock-induced activity and inhibition of LH glutamatergic neurons disrupted VTA VGluT2+VGaT+ tailshock-induced activity. We interpret these results such that inputs to VTA VGluT2+VGaT+ neurons may integrate diverse signals related to the detection and processing of motivationally salient outcomes.