Department of Anatomy and Neurobiology, Program in Neurosciences, University of Maryland School of Medicine, Baltimore, Maryland.
J Neurophysiol. 2020 Mar 1;123(3):1120-1132. doi: 10.1152/jn.00628.2019. Epub 2020 Jan 29.
Short-term plasticity is a fundamental synaptic property thought to underlie memory and neural processing. The glomerular microcircuit comprises complex excitatory and inhibitory interactions and transmits olfactory nerve signals to the excitatory output neurons, mitral/tufted cells (M/TCs). The major glomerular inhibitory interneurons, short axon cells (SACs) and periglomerular cells (PGCs), both provide feedforward and feedback inhibition to M/TCs and have reciprocal inhibitory synapses between each other. Olfactory input is episodically driven by sniffing. We hypothesized that frequency-dependent short-term plasticity within these inhibitory circuits could influence signals sent to higher-order olfactory networks. To assess short-term plasticity in glomerular circuits and MC outputs, we virally delivered channelrhodopsin-2 (ChR2) in glutamic acid decarboxylase-65 promotor (GAD2-cre) or tyrosine hydroxylase promoter (TH-cre) mice and selectively activated one of these two populations while recording from cells of the other population or from MCs. Selective activation of TH-ChR2-expressing SACs inhibited all recorded GAD2-green fluorescent protein(GFP)-expressing presumptive PGC cells, and activation of GAD2-ChR2 cells inhibited TH-GFP-expressing SACs, indicating reciprocal inhibitory connections. SAC synaptic inhibition of GAD2-expressing cells was significantly facilitated at 5-10 Hz activation frequencies. In contrast, GAD2-ChR2 cell inhibition of TH-expressing cells was activation-frequency independent. Both SAC and PGC inhibition of MCs also exhibited short-term plasticity, pronounced in the 5-20 Hz range corresponding to investigative sniffing frequency ranges. In paired SAC and olfactory nerve electrical stimulations, the SAC to MC synapse was able to markedly suppress MC spiking. These data suggest that short-term plasticity across investigative sniffing ranges may differentially regulate intra- and interglomerular inhibitory circuits to dynamically shape glomerular output signals to downstream targets. Short-term plasticity is a fundamental synaptic property that modulates synaptic strength based on preceding activity of the synapse. In rodent olfaction, sensory input arrives episodically driven by sniffing rates ranging from quiescent respiration (1-2 Hz) through to investigative sniffing (5-10 Hz). Here we show that glomerular inhibitory networks are exquisitely sensitive to input frequencies and exhibit plasticity proportional to investigative sniffing frequencies. This indicates that olfactory glomerular circuits are dynamically modulated by episodic sniffing input.
短期可塑性是一种基本的突触特性，被认为是记忆和神经处理的基础。肾小球微电路由复杂的兴奋性和抑制性相互作用组成，将嗅觉神经信号传递到兴奋性输出神经元，即僧帽细胞/丛细胞（M/TCs）。主要的肾小球抑制性中间神经元，短轴细胞（SACs）和旁肾小球细胞（PGCs），都向 M/TCs 提供前馈和反馈抑制，并在彼此之间具有相互抑制性突触。嗅觉输入由嗅探间歇性驱动。我们假设这些抑制性回路中的频率依赖性短期可塑性可以影响发送到高级嗅觉网络的信号。为了评估肾小球回路和 MC 输出中的短期可塑性，我们在谷氨酸脱羧酶-65 启动子（GAD2-cre）或酪氨酸羟化酶启动子（TH-cre）小鼠中病毒传递了通道视紫红质-2（ChR2），并选择性地激活了其中一种群体，同时记录来自另一种群体或 MC 的细胞。选择性激活表达 TH-ChR2 的 SAC 抑制了所有记录的表达 GAD2-绿色荧光蛋白（GFP）的假定 PGC 细胞，而激活 GAD2-ChR2 细胞抑制了表达 TH-GFP 的 SAC，表明存在相互抑制性连接。在 5-10 Hz 的激活频率下，SAC 对 GAD2 表达细胞的突触抑制显著增强。相比之下，GAD2-ChR2 细胞对表达 TH 的细胞的抑制与激活频率无关。SAC 和 PGC 对 MC 的抑制也表现出短期可塑性，在 5-20 Hz 的范围内显著，对应于探查性嗅探频率范围。在配对的 SAC 和嗅觉神经电刺激中，SAC 到 MC 的突触能够显著抑制 MC 的放电。这些数据表明，在探查性嗅探范围内的短期可塑性可能会以不同的方式调节内和外肾小球抑制性回路，以动态塑造下游靶标中的肾小球输出信号。短期可塑性是一种基本的突触特性，根据突触的先前活动来调节突触强度。在啮齿动物嗅觉中，感觉输入间歇性地由嗅探率驱动，从静止呼吸（1-2 Hz）到探查性嗅探（5-10 Hz）。在这里，我们表明，肾小球抑制性网络对输入频率非常敏感，并表现出与探查性嗅探频率成正比的可塑性。这表明嗅觉肾小球回路被间歇性嗅探输入动态调节。
