Thalamic recruitment of feedforward inhibition is known to enhance the fidelity of the receptive field by limiting the temporal window during which cortical neurons integrate excitatory inputs. Feedforward inhibition driven by the mediodorsal nucleus of the thalamus (MD) has been previously observed, but its physiological function and regulation remain unknown. Accumulating evidence suggests that elevated neuronal activity in the prefrontal cortex is required for the short-term storage of information. Furthermore, the elevated neuronal activity is supported by the reciprocal connectivity between the MD and the medial prefrontal cortex (mPFC). Therefore, detailed knowledge about the synaptic connections during high-frequency activity is critical for understanding the mechanism of short-term memory. In this study, we examined how feedforward inhibition of thalamofrontal connectivity is modulated by activity frequency. We observed greater short-term synaptic depression during disynaptic inhibition than in thalamic excitatory synapses during high-frequency activities. The strength of feedforward inhibition became weaker as the stimulation continued, which, in turn, enhanced the range of firing jitter in a frequency-dependent manner. We postulated that this phenomenon was primarily due to the increased failure rate of evoking action potentials in parvalbumin-expressing inhibitory neurons. These findings suggest that the MD-mPFC pathway is dynamically regulated by an excitatory-inhibitory balance in an activity-dependent manner. During low-frequency activities, excessive excitations are inhibited, and firing is restricted to a limited temporal range by the strong feedforward inhibition. However, during high-frequency activities, such as during short-term memory, the activity can be transferred in a broader temporal range due to the decreased feedforward inhibition.

中文翻译：

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频率依赖性门控丘脑额叶突触的前馈抑制。

已知丘脑募集前馈抑制通过限制皮质神经元整合兴奋性输入的时间窗来增强感受野的保真度。先前已经观察到由丘脑的中嗅核（MD）驱动的前馈抑制，但是其生理功能和调节仍然未知。越来越多的证据表明，短期存储信息需要前额叶皮层神经元活动的增强。此外，MD和内侧前额叶皮层（mPFC）之间的相互连接支持了神经元活动的增强。因此，有关高频活动过程中的突触连接的详细知识对于理解短期记忆的机制至关重要。在这个研究中，我们研究了如何通过活动频率调节前馈抑制丘脑额叶连接性。我们观察到在高频活动期间，在突触抑制期间短期丘脑突触抑制比丘脑兴奋性突触更大。随着刺激的继续，前馈抑制的强度变得更弱，从而以频率相关的方式增加了发射抖动的范围。我们推测，这种现象主要是由于表达小白蛋白的抑制性神经元中诱发动作电位的失败率增加。这些发现表明，MD-mPFC途径是由兴奋性抑制平衡以活动依赖性方式动态调节的。在低频活动中，过度的激励被抑制，强烈的前馈抑制将射击限制在有限的时间范围内。但是，在高频活动中，例如在短期记忆中，由于前馈抑制的降低，可以在更宽的时间范围内转移活动。