Dopamine-Induced Depressing Synapses Facilitate Sustained Neural Activities in Prefrontal Cortex: A Simulation Study Yasunobu Igarashi, Yuichi Sakumura, Shin Ishii Nara Institute of Science and Technology, Japan E-mail: yasu-i@is.naist.jp Neurons in the prefrontal cortex (PFC) of monkeys show directional sustained activities during an oculomotor delayed response task. It is experimentally known that this sustained activity is inhibited by dopamine (DA) antagonists applied to PFC [1], on the contrary, its agonists facilitate the depressing effect in excitatory synapses [2]. These experimental results seem to be opposed to each other because DA sustains neural activities while it depresses synaptic efficacy. In this computational study, we demonstrate how depressing synapses (DS) work to maintain sustained neural activities. The model descriptions are summarized as follows (Fig. 1): (1) excitatory neurons in PFC are excited by postparietal cortical neurons which receive resultant stimuli from the visual cortex. (2) excitatory neurons in PFC have recurrent connections, and interact with inhibitory neurons within PFC. (3) activation of DA neurons in midbrain makes excitatory synapses in PFC depressed. This model shows sustained activities of excitatory neurons in PFC, which have a bell shaped dependence on the recurrent connection probability due to feedback inhibition via inhibitory neurons (Fig. 2.). However, the bell shaped activity shifts such to show higher activity for lager connection probability when a depressing effect by DA exists, because depressing synapses lower the effective connectivity of feedback excitation and inhibition. Our simulation results thus suggest that the synaptic depressing effect could facilitate sustained activities in PFC especially if excitatory synapses have dense self-excitatory connections. Depress (1) E E Postparietal cortex I (3) Prefrontal cortex DA Midbrain firing rate [ Hz ] (2) 250 Non Depress 200 150 DS effect 100 50 0 0.2 0.4 0.6 0.8 1 [ connection probability ] Fig. 1. Schematic network architecture. There Fig. 2. Averaged firing rate (sustained activare four neuron groups. E, I, and DA are ex- ity) of excitatory neurons in PFC against the citatory, inhibitory, and DA neurons, respec- recurrent connection probability. tively. Reference [1] Sawaguchi, T. (2000) Parkinsonism Relat. Disord., 7: 9-19. [2] Gao, W.J., Krimer, L.S., Goldman-Rakic, P.S. (2001) Proc. Natl. Acad. Sci. U S A., 98:295-300.