Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior.
Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior.
复制标题
DOI：
10.1007/s00429-021-02288-7
复制
发表时间：
2021-07
影响因子：
3.1
通讯作者：
Brown RE
中科院分区：
文献类型：
--
作者：
McKenna JT;Yang C;Bellio T;Anderson-Chernishof MB;Gamble MC;Hulverson A;McCoy JG;Winston S;Hodges E;Katsuki F;McNally JM;Basheer R;Brown RE
基底前脑（BF）参与唤醒，注意和奖励处理，但个别BF神经元亚型的作用仍有待发现。谷氨酸能神经元是三种主要BF神经递质表型中最不为人所知的。在这里，我们分析了分布，大小，钙结合蛋白含量和预测的主要群体的BF谷氨酸能神经元表达囊泡谷氨酸转运子亚型2（vGluT 2）和测试的功能激活它们的影响。将在vGluT 2启动子控制下表达Cre重组酶的小鼠与表达红色荧光蛋白tdTomato的报告菌株杂交，以产生vGluT 2-cre-tdTomato小鼠。胆碱乙酰转移酶的免疫组织化学染色和与在GABA能神经元中选择性表达绿色荧光蛋白的小鼠的交叉证实胆碱能、GABA能和vGluT 2+神经元代表不同的BF亚群。BF vGluT 2+神经元的亚群表达钙结合蛋白calbindin或calretinin，表明BF vGluT 2+神经元存在多种亚型。顺行追踪使用腺相关病毒载体表达channelrhodopsin 2增强黄色荧光融合蛋白揭示了主要的预测BF vGluT 2+神经元相邻的BF胆碱能和小白蛋白神经元，以及额外的BF领域参与控制的唤醒或厌恶/奖励行为，如外侧缰和腹侧被盖区。BF vGluT 2神经元的光遗传激活引起了显着的避免给予刺激的区域，而BF小清蛋白或胆碱能神经元的刺激没有。与先前的光遗传学研究结果表明唤醒促进作用一起，我们的研究结果表明BF vGluT 2神经元在促进觉醒和回避行为中起双重作用。
The basal forebrain (BF) is involved in arousal, attention, and reward processing but the role of individual BF neuronal subtypes is still being uncovered. Glutamatergic neurons are the least well-understood of the three main BF neurotransmitter phenotypes. Here we analyzed the distribution, size, calcium-binding protein content and projections of the major group of BF glutamatergic neurons expressing the vesicular glutamate transporter subtype 2 (vGluT2) and tested the functional effect of activating them. Mice expressing Cre recombinase under control of the vGluT2 promoter were crossed with a reporter strain expressing the red fluorescent protein, tdTomato, to generate vGluT2-cre-tdTomato mice. Immunohistochemical staining for choline acetyltransferase and a cross with mice expressing green fluorescent protein selectively in GABAergic neurons confirmed cholinergic, GABAergic and vGluT2+ neurons represent distinct BF subpopulations. Subsets of BF vGluT2+ neurons expressed the calcium binding proteins calbindin or calretinin, suggesting multiple subtypes of BF vGluT2+ neurons exist. Anterograde tracing using adeno-associated viral vectors expressing channelrhodopsin2-enhanced yellow fluorescent fusion proteins revealed major projections of BF vGluT2+ neurons to neighboring BF cholinergic and parvalbumin neurons, as well as to extra-BF areas involved in the control of arousal or aversive/rewarding behavior such as the lateral habenula and ventral tegmental area. Optogenetic activation of BF vGluT2 neurons elicited a striking avoidance of the area where stimulation was given, whereas stimulation of BF parvalbumin or cholinergic neurons did not. Together with previous optogenetic findings suggesting an arousal-promoting role, our findings suggest BF vGluT2 neurons play a dual role in promoting wakefulness and avoidance behavior.
登录
查看更多内容
影响因子：
8.8
作者：
Faget L;Osakada F;Duan J;Ressler R;Johnson AB;Proudfoot JA;Yoo JH;Callaway EM;Hnasko TS
通讯作者：
Hnasko TS
影响因子：
16.6
作者：
Anaclet C;Pedersen NP;Ferrari LL;Venner A;Bass CE;Arrigoni E;Fuller PM
通讯作者：
Fuller PM
影响因子：
2.3
作者：
FORLONI, G;GRZANNA, R;COYLE, JT
通讯作者：
COYLE, JT
影响因子：
25
作者：
Eban-Rothschild A;Rothschild G;Giardino WJ;Jones JR;de Lecea L
通讯作者：
de Lecea L
影响因子：
5.3
作者：
Baker, Phillip M.;Jhou, Thomas;Vicentic, Aleksandra
通讯作者：
Vicentic, Aleksandra