UC San Diego

For years it was thought that a neuron releases only a single neurotransmitter for the entirety of its life. Recent research, however, has provided evidence that neurons can change the neurotransmitters they synthesize based on activity within a circuit. This phenomenon, referred to as "activity-dependent neurotransmitter respecification," is thought to be a homeostatic process that prevents over-excitation or over-inhibition within a circuit. I searched for population-level transmitter respecification in response to sleep/wake cycles. Sprague- Dawley rats were housed in a 12 hr light : 12 hr dark cycle. They were sacrificed after most time spent awake or most time spent asleep to look for differences in the number of neurons expressing specific transmitters between the two time points. In situ hybridization was performed on separate but adjacent sections to label cells that express the mRNA encoding glutamic acid decarboxylase (GAD65 - an enzyme involved in the synthesis of GABA), or cortistatin (CST-14 - a neuropeptide expressed in cortical GABAergic interneurons involved in sleep). Cell populations in the primary motor cortex were compared between end of sleep and end of wake using stereology. No significant differences were observed in the CST-14+ population between sleep and wake. The GAD65+ population was 20-30% larger (p < 0.05) in animals sacrificed at the end of wake than those sacrificed at the end of sleep. My findings are consistent with transmitter switching, but a complementary change in another transmitter population must be observed in order to attribute them to neurotransmitter respecification