Histamine Release in the Prefrontal Cortex Excites Fast-Spiking Interneurons while GABA Released from the Same Axons Inhibits Pyramidal Cells.
Histamine Release in the Prefrontal Cortex Excites Fast-Spiking Interneurons while GABA Released from the Same Axons Inhibits Pyramidal Cells.
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DOI：
10.1523/jneurosci.0936-22.2022
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发表时间：
2023-01-11
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我们研究了来自下丘脑结节乳头核（TMN）并投射到前额叶皮层（PFC）的轴突释放组胺和GABA如何影响回路加工。我们从表达组氨酸脱羧酶基因的遗传定义的TMN轴突（TMNHDC轴突）中光刺激组胺/GABA。采用全细胞记录技术，观察了雄性和雌性小鼠前边缘（PL）、前扣带（AC）和边缘下（IL）区2/3层PFC神经元在光刺激组胺/GABA释放前后的兴奋性。我们发现，组胺-GABA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，组胺释放TMNHDC轴突诱导的附加增益的变化，这是阻断组胺H1和H2受体拮抗剂。PFC中其他快速发放的中间神经元的兴奋性没有改变。与此相反，从TMNHDC轴突释放的GABA主要产生分裂的增益变化PyrNs，增加他们的静息输入电导，并降低斜率的输入-输出关系。这种对PyrNs的抑制作用不被组胺受体拮抗剂阻断，但被GABAA受体拮抗剂阻断。在整个成年期（从3个月到18个月），从PFC中的TMNHDC轴突释放的GABA在老年小鼠中显著抑制PyrN兴奋性。对于那些在晚年保持认知能力的个体来说，在衰老过程中TMNHDC对PyrNs的GABA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 histamine and GABA release from axons originating from the hypothalamic tuberomammillary nucleus (TMN) and projecting to the prefrontal cortex (PFC) influences circuit processing. We opto-stimulated histamine/GABA from genetically-defined TMN axons that express the histidine decarboxylase gene (TMNHDC axons). Whole-cell recordings from PFC neurons in layer 2/3 of prelimbic (PL), anterior cingulate (AC) and infralimbic (IL) regions were used to monitor excitability before and after opto-stimulated histamine/GABA release in male and female mice. We found that histamine-GABA release influences the PFC through actions on distinct neuronal types: the histamine stimulates fast-spiking interneurons; and the released GABA enhances tonic (extrasynaptic) inhibition on pyramidal cells (PyrNs). For fast spiking non-accommodating interneurons, histamine released from TMNHDC axons induced additive gain changes, which were blocked by histamine H1 and H2 receptor antagonists. The excitability of other fast-spiking interneurons in the PFC was not altered. In contrast, the GABA released from TMNHDC axons predominantly produced divisive gain changes in PyrNs, increasing their resting input conductance, and decreasing the slope of the input-output relationship. This inhibitory effect on PyrNs was not blocked by histamine receptor antagonists but was blocked by GABAA receptor antagonists. Across the adult lifespan (from 3 months to 18 months of age), the GABA released from TMNHDC axons in the PFC inhibited PyrN excitability significantly more in older mice. For individuals that maintain cognitive performance into later life, the increases in TMNHDC GABA modulation of PyrNs during ageing could enhance information processing and be an adaptive mechanism to buttress cognition.
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