Postdoctoral Training Program in Functional Neurogenomics

Neural mechanisms of photoperiodic programming of the dorsal raphe serotonin neurons. Although several studies have determined that day length (photoperiod) can impact neurobehavioral disorders, such as depression, the underlying mechanisms for this effects are not clear. Work from our laboratory has previously shown that seasonal photoperiods have long-lasting effects on the firing rate of mouse serotonergic neurons of the dorsal raphe and affective behaviors. Mice exposed to "long" (16:8 LD cycle) photoperiod exhibit higher firing rate of serotonergic neurons and perform better in behavioral tasks used to measure depression and anxiety. In contrast, mice raised under "short" (8:16 LD cycle) photoperiod present less firing of serotonin neurons and perform poorly in these behavioral tasks. The goal of the current project is to examine how changes in key K+ and Ca++ currents in the dorsal raphe neurons contribute to the observed differences in firing rate between photoperiods. To test the contribution of these currents, we will measure firing rate of raphe neurons using multielectrode array recordings and whole cell patch clamp recordings where we pharmacologically inhibit specific K+ and Ca++ channels. Previous work on TREK-1, a twin-pore K+ channel that is highly expressed in dorsal raphe neurons, showed that knockout mice present an increased 5-HT neuron spike rate and decreased depression-like behaviors, effectively phenocopying our long photoperiod mice. Based on this result, we hypothesize that the photoperiod-induced depolarization of 5-HT neurons may be due in part to changes in the expression or function of TREK-1 and other channels in serotonergic cells. We expect that the completion of this experiments will reveal neuronal and synaptic pathways for photoperiod programming of the 5-HT neurons in the dorsal raphe neurons, which may potentially provide novel targets for the treatment of neurobehavioral disorders.