Frontoparietal inputs are necessary for sustained activity in the PPC during short-term memory

초록

Short-term memory (STM), the transient storage and maintenance of information, is a fundamental cognitive process. While previous studies have underscored the role of long-range synaptic connections within the prefrontal cortex (PFC) and the influence of diverse neuromodulators on sustaining neuronal activity and STM, the impact of reciprocal connectivity with the posterior parietal cortex (PPC) on sustained neuronal activity during working memory remains unclear. In this study, we elucidated the dynamic interplay between the PFC and the PPC, shedding light on the mechanisms underlying sustained neuronal firing during short-term memory. Our findings reveal direct and robust synaptic connections from the PFC to the PPC, wherein high-frequency activity of the PFC elicits membrane depolarization in PPC neurons. Notably, we found that cholinergic activation, in conjunction with frontoparietal synaptic activity, induces sustained neuronal firing within the PPC that persists for several seconds. To explore the functional significance of this phenomenon, we employed pharmacological and optogenetic techniques to inhibit frontoparietal synapses or to block muscarinic acetylcholine receptors (mAChRs). Remarkably, the inhibition of frontoparietal synapses or blockage of mAChRs led to a marked decline in performance on a delayed Y-maze task, a behavioral paradigm reliant on STM. Furthermore, We recorded neuronal activity during the behavior task to verify the difference in firing rate during the task and changes of frequency after blockage of acetylcholine release during delay period. These results suggest that the maintenance of sustained activity in the PPC through frontoparietal circuitry, coupled with mAChR activation, represents a critical factor in short-term memory processes. This investigation enhances our understanding of the intricate mechanisms governing STM by elucidating the reciprocal interactions between the PFC and the PPC. Furthermore, it highlights the importance of muscarinic acetylcholine receptor activation in sustaining PPC neuronal firing and its impact on STM performance.