UCSF

The prefrontal cortex (PFC) functions to integrate information from the internal and external world in order to flexibly guide behavior. As the most recently evolved brain region, the PFC is implicated in a range of psychiatric disorders such as depression, anxiety, and schizophrenia. The circuitry within the PFC consists of a diversity of excitatory and inhibitory neurons and each neuronal subtype represents a unique locus for action by neuromodulators, such as dopamine and serotonin. The serotonergic system is heavily implicated in mood and emotion and is the target of many modern psychiatric drugs. Despite this, we have a limited understanding of the actions of serotonin on the diverse cell types in the PFC. In this dissertation, I describe the actions of serotonin (5HT) on interneurons and excitatory inputs arriving from discrete brain regions and suggest how this may relate to behavior and disease. I find that 5HT increases the excitability of fast-spiking interneurons but not somatostatin-expressing interneurons by reducing conductance through potassium channels, leading to enhanced summation of gamma frequency inputs. Furthermore, this causes an increase in gamma-frequency inhibitory events in downstream pyramidal cells, a finding which may contribute to my observation that serotonergic signaling reduces low frequency oscillatory power without changing in gamma power in vivo. I also describe how serotonin may act at multiple loci within the prefrontal circuit to reduce anxiety behavior. By both presynaptically suppressing ventral hippocampal inputs and increasing inhibition, 5HT may reduce theta oscillations and attenuate anxiety behavior. These findings may have wide implications for our understanding of psychiatric disorders.