Inhibitory Interneurons in the Mediodorsal Nucleus of the Thalamus and their Modulation andTermination of Short-Term Memory

초록

Short-term memory (STM), the ability to temporarily retain and manipulate information, relies on coordinated thalamofrontal dynamics. The mediodorsal nucleus (MD) of the thalamus, through its reciprocal connections with the medial prefrontal cortex (mPFC), plays a key role in maintaining delay-period activity during STM tasks. Given the limited capacity of STM, unloading and refreshing the retained information after the need should be equally important. However, the mechanisms underlying the modulation and termination of STM remain unexplored. In this study, we identified a population of parvalbumin-expressing (PV+) inhibitory interneurons within the MD thalamus and characterized their intrinsic electrophysiological properties using whole-cell patch-clamp recordings. MD inhibitory (MDIN) neurons exhibited narrower and higher frequency action potential than MD excitatory (MDEX) neurons and facilitated by high-frequency inputs from mPFC. Further, strong and reliable inhibitory synaptic inputs were found on the MDEX neurons. In line with this, high-frequency activity of the mPFC afferents activated MDIN neurons, which in turn inhibited nearby excitatory neurons. Despite the sparsity of the MDIN neurons, this inhibition was achieved through robust and reliable synaptic connections, effectively suppressing excitatory activity within the MD thalamus. Synaptophysin-mRuby labeling revealed dendro-dendritic synapses among MDIN neurons, indicating local inhibitory interactions within the MD thalamus. These findings suggest that the MDIN neurons regulate STM by responding selectively to sustained cortical input through feedforward dendro-dendritic inhibition, thereby ensuring its timely termination by suppressing MDEX neurons. Importantly, this study provides the first direct evidence of PV+ inhibitory interneurons within the MD thalamus. Our findings suggested MDIN neurons as a novel mechanism for controlling both the maintenance and termination of STM, offering a new perspective on thalamocortical dynamics.