Department of Psychiatry, University of California, San Francisco, San Francisco, United States; Department of Neurology, University of California, San Francisco, San Francisco, United States; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States
Roy Ben-Shalom
Department of Neurology, University of California, San Francisco, San Francisco, United States; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Caroline M Keeshen
Department of Neurology, University of California, San Francisco, San Francisco, United States; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Department of Psychiatry, University of California, San Francisco, San Francisco, United States; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Department of Neurology, University of California, San Francisco, San Francisco, United States; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
The medial prefrontal cortex plays a key role in higher order cognitive functions like decision making and social cognition. These complex behaviors emerge from the coordinated firing of prefrontal neurons. Fast-spiking interneurons (FSIs) control the timing of excitatory neuron firing via somatic inhibition and generate gamma (30–100 Hz) oscillations. Therefore, factors that regulate how FSIs respond to gamma-frequency input could affect both prefrontal circuit activity and behavior. Here, we show that serotonin (5HT), which is known to regulate gamma power, acts via 5HT2A receptors to suppress an inward-rectifying potassium conductance in FSIs. This leads to depolarization, increased input resistance, enhanced spiking, and slowed decay of excitatory post-synaptic potentials (EPSPs). Notably, we found that slowed EPSP decay preferentially enhanced temporal summation and firing elicited by gamma frequency inputs. These findings show how changes in passive membrane properties can affect not only neuronal excitability but also the temporal filtering of synaptic inputs.
