Frontoparietal as well as cholinergic inputs are necessary for the activity of the posterior parietal cortex during short-term memory

초록

Working memory (WM), the transient storage and maintenance of information, is a fundamental cognitive process. While previous studies have highlighted the importance of long-range synaptic connections within the prefrontal cortex (PFC) and posterior parietal cortex (PPC), as well as the modulatory role of acetylcholine (ACh), it remains unclear how neuromodulatory signals and interareal connectivity cooperate to sustain neuronal activity during short-term memory (STM). In this study, we investigated the functional significance of frontoparietal synapses—specifically, PFC-driven inputs to the PPC—and examined how ongoing frontoparietal activity contributes to sustained PPC activity during STM. Our findings demonstrate that the PFC provides direct and robust excitatory input to the PPC, such that high-frequency PFC activity evokes membrane depolarization in PPC neurons via strong monosynaptic connections.Strikingly, we also found that cholinergic activation induces autonomous persistent firing in PPC neurons, with activity lasting for several seconds. To assess the behavioral relevance of these inputs, we used optogenetic inhibition of frontoparietal synapses and pharmacological blockade of muscarinic ACh receptors (mAChRs). Both manipulations significantly impaired performance on a delayed Y-maze task, which depends on intact STM. To further investigate the circuit mechanisms, we recorded PPC neural activity during a delayed Y-maze task. In correct trials, PPC neurons exhibited direction-selective firing during the delay period. However, inhibition of either frontal or cholinergic inputs led to a significant reduction in PPC delay activity and a marked decrease in direction-selective neural responses.Together, our findings suggest that inputs from the PFC and cholinergic systems are critical for sustaining direction-selective neural activity in the PPC, and that this frontoparietal–cholinergic interaction plays a vital role in supporting short-term memory.