The role of short-term dynamics in the modulation of MD-PFC activity-loop

Abstract

Persistent neural activity in the prefrontal cortex has been broadly inspired as the substrate of short-term memory for perceptual decision making. Recent studies have shown that reciprocal excitation of the mediodorsal nucleus (MD) of the thalamus and frontal cortices supports the persistent activity during the short-term memory. However, little is known how the neurons in the prefrontal cortex maintain the activity. Although MD-driven disynaptic feedforward inhibition in the medial prefrontal cortex (mPFC) has been reported to determine the time window of integration of excitatory synaptic inputs, it has never been examined how feedforward inhibition is modulated during the persistent activity. We examined whether the integration time window is changed by the consecutive thalamic activity by using whole-cell patch clamp recording with optogenetic stimulation of thalamocortical axons. We observed the greater short-term synaptic depression in disynaptic inhibition compared with thalamic excitatory synapses during high-frequency (5-10 Hz) stimulation. Consequently, the strength of the feedforward inhibition becomes weaker as the stimulation continues, which, in turn, enhances the range of firing jitter in the frequency dependent way. These findings suggest that MD-mPFC pathway is dynamically regulated by the excitatory-inhibitory balance in an activity-dependent manner. During low-frequency, excessive excitation is inhibited, and firing is restricted in limited temporal range by the strong feedforward inhibition. Whereas during high-frequency, such as in case of during the short-term memory, the excitation transfer will be enabled to occur in broader temporal range by the decreased feed-forward inhibition.