Rhythmic expression of a cAMP phosphodiesterase switches neuronal excitability states in the mammalian suprachiasmatic nucleus

How the transcriptome of a neuron determines its electrophysiological properties and how this change in different contexts are major questions in neurobiology. The intracellular molecular clocks in the circadian pacemaker neurons in the mammalian suprachiasmatic nucleus (SCN) drive 24hr rhythms in clock gene expression via a transcriptional-translational feedback loop ^1,2 . These molecular clocks also control 24hr rhythms in the firing of SCN neurons ^3–5 – a subset of which enter a silent depolarized state around midday ⁶ . We used single-cell RNA sequencing and identified that the Avp⁺ / Nms⁺ and Vip⁺ / Nms⁺ are the SCN neurons that undergo daytime silencing. We also found high level and rhythmic expression of the Pde10a phosphodiesterase in these Nms⁺ SCN neurons. Acutely inhibiting Pde10a activity or elevating intracellular cAMP – to bypass high Pde10a levels – specifically shifts these Nms+ SCN neurons into a depolarized silent state hours ahead of schedule. A similar mechanism may occur in other neurons that switch to silent depolarized states.