Synaptic alterations in pyramidal cells following genetic manipulation of neuronal excitability in monkey prefrontal cortex.

The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in primate cognition, integrating multimodal information to generate top-down signals for cognitive control. During cognitive tasks, the DLPFC displays activity patterns of exceptional complexity and duration not observed in other cortical areas or species. These activity patterns are likely associated with the unique physiological and morphological properties of primate DLPFC pyramidal neurons (PNs). However, little is known about how the distinctive activity of the primate DLPFC regulates the unique properties of its PNs. To test whether manipulating neuronal excitability in area 46 of the rhesus monkey DLPFC affects synaptic inputs onto PNs, we used adeno-associated viral vector (AAV)-mediated overexpression of Kir2.1 channels, a genetic silencing tool previously shown to decrease neuronal excitability and firing activity . At 7 to 12 weeks post-AAV microinjections into DLPFC area 46, we assessed the effects of Kir2.1 overexpression using patch clamp recordings from PNs in acute slices. We found that Kir2.1 overexpression significantly reduced PN excitability via the effects of the AAV-encoded Kir2.1 channels. Moreover, recordings of synaptic currents showed that Kir2.1 overexpression significantly reduced excitatory synaptic strength without affecting inhibitory synapses. Thus, we show for the first time that changing neuronal excitability with recombinant DNA tools delivered via AAVs can efficiently modify synaptic properties in the primate neocortex. Moreover, we report that manipulating neuronal excitability affects synaptic properties in ways that seem to differ between the primate DLPFC network and the rodent cortex.