Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition

Experimental evidence suggests that the maintenance of an item in working m emory is achieved through persistent activity in selective neural assemblie s of the cortex. To understand the. mechanisms underlying this phenomenon, it is essential to investigate how persistent activity is affected by exter nal inputs or neuromodulation. We have addressed these questions using a re current network model of object working memory. Recurrence is dominated by inhibition, although persistent activity is generated through recurrent exc itation in small subsets of excitatory neurons. Our main findings are as follows. (1) Because of the strong feedback inhibi tion, persistent activity shows an inverted U shape as a function of increa sed external drive to the network. (2) A transient external excitation can switch off a network from a selective persistent state to its spontaneous s tate. (3) The maintenance of the sample stimulus in working memory is not a ffected by intervening stimuli (distractors) during the delay period, provi ded the stimulation intensity is not large. On the other hand, if stimulati on intensity is large enough, distractors disrupt sample-related persistent activity, and the network is able to maintain a memory only of the last sh own stimulus. (4) A concerted modulation of GABAA and NMDA conductances lea ds to a decrease of spontaneous activity but an increase of persistent acti vity; the enhanced signal-to-noise ratio is shown to increase the resistanc e of the network to distractors. (5) Two mechanisms are identified that pro duce an inverted U shaped dependence of persistent activity on modulation. The present study therefore points to several mechanisms that enhance the s ignal-to-noise ratio in working memory states. These mechanisms could be im plemented in the prefrontal cortex by dopaminergic projections from the mid brain.