Ly Annie, Karnosky Rachel, Prévost Emily D, Hotchkiss Hayden, Pelletier Julianne, Spencer Robert L, Ford Christopher P, Root David H
Department of Psychology and Neuroscience, University of Colorado Boulder, 2860 Wilderness Pl, Boulder, CO 80301.
Deparment of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045.
bioRxiv. 2025 Jan 2:2025.01.01.631003. doi: 10.1101/2025.01.01.631003.
The bed nucleus of the stria terminalis (BNST) is involved in feeding, reward, aversion, and anxiety-like behavior. We identify BNST neurons defined by the expression of vesicular glutamate transporter 3, VGluT3. VGluT3 neurons were localized to anteromedial BNST, were molecularly distinct from accumbal VGluT3 neurons, and co-express vesicular GABA transporter (VGaT). Cell-type specific presynaptic processes were identified in arcuate nucleus (ARC) and the paraventricular nucleus of the hypothalamus (PVN), regions critical for feeding and homeostatic regulation. Whole-cell patch-clamp electrophysiology revealed that, while these neurons co-express VGluT3 and VGaT, they functionally transmit GABA to both ARC and PVN, with rare glutamate co-transmission to ARC. Neuronal recordings of VGluT3 BNST neurons showed greater calcium-dependent signaling in response to sucrose consumption while sated compared with fasted. When fasted, optogenetic stimulation of BNST VGluT3 neurons decreased sucrose consumption using several stimulation conditions but not when stimulation occurred prior to sucrose access, suggesting that BNST VGluT3 activation concurrent with consumption in the fasted state reduces feeding. BNST VGluT3 activation during anxiety-like paradigms (novelty-suppressed feeding, open field, and elevated zero maze) and real-time place conditioning resulted in no changes in anxiety-like or reward/aversion behavior. We interpret these data such that VGluT3 BNST neurons represent a unique cellular population within the BNST that provides inhibitory input to hypothalamic regions to decrease feeding without affecting anxiety-like or reward/aversion behavior.
终纹床核（BNST）参与进食、奖赏、厌恶和焦虑样行为。我们鉴定了由囊泡型谷氨酸转运体3（VGluT3）表达所定义的BNST神经元。VGluT3神经元定位于前内侧BNST，在分子水平上与伏隔核中的VGluT3神经元不同，并且共表达囊泡型GABA转运体（VGaT）。在弓状核（ARC）和下丘脑室旁核（PVN）中鉴定出了细胞类型特异性的突触前过程，这两个区域对进食和稳态调节至关重要。全细胞膜片钳电生理学研究表明，虽然这些神经元共表达VGluT3和VGaT，但它们在功能上向ARC和PVN传递GABA，仅有极少的谷氨酸共同传递至ARC。对VGluT3 BNST神经元的神经元记录显示，与禁食时相比，在饱腹状态下对蔗糖消耗的反应中，其钙依赖性信号更强。禁食时，在几种刺激条件下，对BNST VGluT3神经元进行光遗传学刺激会减少蔗糖消耗，但在蔗糖获取之前进行刺激则不会，这表明在禁食状态下与消耗同时发生的BNST VGluT3激活会减少进食。在焦虑样范式（新奇抑制进食、旷场试验和高架零迷宫试验）和实时位置条件反射过程中激活BNST VGluT3，不会导致焦虑样或奖赏/厌恶行为发生变化。我们对这些数据的解读是，VGluT3 BNST神经元代表BNST内一个独特的细胞群体，该群体向下丘脑区域提供抑制性输入，以减少进食，而不影响焦虑样或奖赏/厌恶行为。
