毒蕈碱信号通过维持丘脑驱动来保持前额叶皮层的延迟期选择性
Muscarinic signaling sustains delay-period selectivity in prefrontal cortex by preserving thalamic drive
短期记忆（STM）需要在前额叶皮层（PFC）中临时维持与任务相关的信息。丘脑背内侧核（MD）与PFC之间的相互交互被认为参与维持这种活动，但在重复性突触传递的生物物理约束下，丘脑-前额叶通讯如何得以维持仍不清楚。在此，我们表明MD--PFC突触表现出显著的频率依赖性短期抑制，导致重复的丘脑输入逐渐丧失驱动PFC神经元的能力。在STM执行过程中，线索呈现后PFC中的乙酰胆碱（ACh）水平迅速升高，并在整个延迟期内保持升高。毒蕈碱型ACh受体（mAChR）激活并未缓解突触抑制，而是增加了PFC神经元的固有兴奋性，从而保持其对减弱的丘脑输入的响应能力。相反，mAChR阻断损害了STM执行，并在单神经元和群体水平上逐步破坏延迟期的方向性表征，同时 largely 保留了初始编码。这些发现将毒蕈碱信号确定为一个突触后增益机制，该机制补偿了下降的丘脑-前额叶效能，并在STM期间维持与任务相关的前额叶表征。
把丘脑输入到前额叶的突触短时程抑制与毒蕈碱增益放在同一回路里解释延迟期表征的维持。
Short-term memory (STM) requires the temporary maintenance of task-relevant information in prefrontal cortex (PFC). Reciprocal interactions between the mediodorsal thalamus (MD) and PFC have been implicated in sustaining this activity, but how thalamofrontal communication is maintained despite the biophysical constraints of repetitive synaptic transmission remains unclear. Here, we show that MD--PFC synapses exhibit profound frequency-dependent short-term depression, causing repetitive thalamic input to progressively lose its ability to drive PFC neurons. During STM performance, acetylcholine (ACh) levels in PFC rose rapidly following cue presentation and remained elevated throughout the delay period. Muscarinic ACh receptor (mAChR) activation did not alleviate synaptic depression, but instead increased the intrinsic excitability of PFC neurons, thereby preserving their responsiveness to weakened thalamic input. Conversely, mAChR blockade impaired STM performance and progressively disrupted delay-period directional representations at both the single-neuron and population levels, while largely sparing initial encoding. These findings identify muscarinic signaling as a postsynaptic gain mechanism that compensates for declining thalamofrontal efficacy and sustains task-relevant prefrontal representations during STM.
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来源：bioRxiv · Neuroscience · biorxiv.org