Co-release of histamine and GABA in prefrontal cortex excites fast-spiking interneurons and causes divisive gain change in pyramidal cells; an effect that is enhanced in older mice
Co-release of histamine and GABA in prefrontal cortex excites fast-spiking interneurons and causes divisive gain change in pyramidal cells; an effect that is enhanced in older mice
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前额皮质中组胺和 GABA 的共同释放会刺激快速尖峰的中间神经元，并引起锥体细胞的分裂增益变化；
DOI：
10.1101/2022.03.11.483936
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Lucaci D
中科院分区：
文献类型：
--
作者：
Lucaci D
我们研究了共同释放组胺/GABA的轴突起源于下丘脑结节乳头核（TMN）和投射到前额叶皮层（PFC）的影响电路处理。我们光刺激组胺/GABA共同释放从遗传定义的TMN轴突表达组氨酸脱羧酶基因（TMNHDCaxons）。全细胞记录被用来监测视觉识别的PFC神经元的前边缘（PL），前扣带（AC）和边缘下（IL）区域的2/3层的兴奋性之前和之后的光刺激组胺/GABA的释放。我们发现，组胺-GABA共同释放影响PFC通过不同的神经元类型的行动：组胺刺激快速尖峰interneurons;和共同释放的GABA增强强直（突触外）抑制锥体细胞（PyrNs）。对于快速尖峰非调节性中间神经元，光刺激增加兴奋性，组胺H1和H2受体拮抗剂阻断的效果。其他类型的中间神经元在PFC的兴奋性没有改变。相比之下，组胺和GABA共同释放TMNHDCaxons的联合作用产生主要分裂增益变化PyrNs，增加其静息输入电导，并降低输入-输出关系的斜率。TMNHDCaxon激活对PyrNs的直接抑制作用不被组胺受体拮抗剂阻断，但被GABA A受体拮抗剂阻断。在整个成年期（从3个月到2岁以上），刺激PFC中的TMNHDCaxons抑制PyrN兴奋性显着更年长的小鼠。对于那些在以后的生活中保持认知能力的个体，PyrNs的TMNHDC调节的增加可以增强信息处理，并成为支持认知的适应机制。
We studied how co-release of histamine/GABA from axons originating from the hypothalamic tuberomammillary nucleus (TMN) and projecting to the prefrontal cortex (PFC) influences circuit processing. We opto-stimulated histamine/GABA co-release from genetically defined TMN axons that express the histidine decarboxylase gene (TMNHDCaxons). Whole-cell recordings were used to monitor excitability of visually identified PFC neurons in layer 2/3 of prelimbic (PL), anterior cingulate (AC) and infralimbic (IL) regions before and after opto-stimulated histamine/GABA release. We found that histamine-GABA co-release influences the PFC through actions on distinct neuronal types: histamine stimulates fast-spiking interneurons; and co-released GABA enhances tonic (extrasynaptic) inhibition on pyramidal cells (PyrNs). For fast spiking non-accommodating interneurons, opto-stimulation increased excitability, an effect blocked by histamine H1 and H2 receptor antagonists. The excitability of other interneuron types in the PFC was not altered. In contrast, the combined action of histamine and GABA co-release from TMNHDCaxons produced predominantly divisive gain changes in PyrNs, increasing their resting input conductance, and decreasing the slope of the input-output relationship. The direct inhibitory effect of TMNHDCaxon activation on PyrNs was not blocked by histamine receptor antagonists but was blocked by GABAAreceptor antagonists. Across the adult lifespan (from 3 months to over 2 years of age), stimulation of TMNHDCaxons in the PFC inhibited PyrN excitability significantly more in older mice. For individuals that maintain cognitive performance into later life, increases in TMNHDCmodulation of PyrNs could enhance information processing and be an adaptive mechanism to buttress cognition.
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DOI：
10.1523/jneurosci.2931-12.2012
发表时间：
2012-09-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Zecharia AY;Yu X;Götz T;Ye Z;Carr DR;Wulff P;Bettler B;Vyssotski AL;Brickley SG;Franks NP;Wisden W
通讯作者：
Wisden W
大鼠大脑中存在组胺能神经元系统的证据：免疫组织化学分析
影响因子：
2.5
作者：
Takehiko Watanabe;Y. Taguchi;H. Hayashi;J. Tanaka;Sadao Shiosaka;M. Tohyama;H. Kubota;Y. Terano;H. Wada
通讯作者：
H. Wada
影响因子：
3.5
作者：
BAYLISS D A;WANG Y-M;MILLHORN D E
通讯作者：
MILLHORN D E
影响因子：
5.6
作者：
Scammell TE;Jackson AC;Franks NP;Wisden W;Dauvilliers Y
通讯作者：
Dauvilliers Y
影响因子：
4.6
作者：
Naganuma F;Nakamura T;Kuroyanagi H;Tanaka M;Yoshikawa T;Yanai K;Okamura N
通讯作者：
Okamura N