TrkB受体依赖的PV神经元调控小鼠视觉方位辨别能力的机制

TrkB receptor-dependent PV neurons regulate visual orientation discrimination in mice

摘要:

神经营养因子-酪氨酸受体激酶B （tyrosine receptor kinase B，TrkB）信号通路在调控初级视皮层（primary visual cortex，V1）兴奋与抑制平衡上发挥着重要的作用，以往的研究揭示了其通过增加兴奋性传递效率来调控皮层兴奋性水平的机制，却并未阐明TrkB受体如何通过抑制系统来调控兴奋与抑制平衡，进而影响视觉皮层功能。为了探讨TrkB信号通路如何特异性地调控最主要的抑制性神经元——PV神经元进而对小鼠视觉皮层功能产生影响，本研究通过病毒特异性地降低V1区的PV神经元上TrkB受体的表达水平，并通过在体多通道电生理手段记录初级视皮层抑制性与兴奋性神经元功能变化，通过行为学实验测试小鼠的方位辨别能力改变。结果表明，初级视觉皮层中的PV抑制性神经元上的TrkB受体表达减少会显著增加兴奋性神经元的反应强度，减弱抑制性神经元与兴奋性神经元的方位辨别能力，增加二者的信噪比，但是小鼠个体水平的方位辨别能力出现下降。这些结果说明，TrkB信号通路并非单纯通过增加靶向PV神经元的兴奋性传递来调控PV神经元的功能，其对神经元信噪比的影响也并非由于抑制系统的增强所致。

Abstract:

The neurotrophin-tyrosine receptor kinase B (TrkB) signaling pathway plays an important role in regulating the balance of excitation and inhibition in the primary visual cortex (V1). Previous studies have revealed its mechanism of regulating the level of cortical excitability by increasing the efficiency of excitatory transmission, but it has not been elucidated how TrkB receptors regulate the balance of excitation and inhibition through the inhibitory system, which in turn affects visual cortex function. Therefore, the objective of this study was to investigate how the TrkB signaling pathway specifically regulates the most important inhibitory neuron-PV neurons affects the visual cortex function of mice. The expression of TrkB receptor on PV neurons in the V1 region was specifically reduced by the virus, the functional changes of inhibitory and excitatory neurons in the primary visual cortex were recorded by multi-channel electrophysiological in vivo. The orientation discrimination ability of mice was tested by behavioral experiments, and altered orientation discrimination ability of mice was tested by behavioral experiments. The results showed that reduced expression of TrkB receptors on PV inhibitory neurons in primary visual cortex significantly increased the response intensity of excitatory neurons, reduced the orientation discrimination ability of inhibitory and excitatory neurons, and increased the signal-to-noise ratio, but the orientation discrimination ability at the individual level in mice showed a decrease. These results suggest that the TrkB signaling pathway does not modulate the function of PV neurons solely by increasing excitatory transmission targeting PV neurons, and its effect on neuronal signal-to-noise ratio is not due to enhancement of the inhibitory system.