Phase resetting light pulses induce Per1 and persistent spike activity in a subpopulation of biological clock neurons.

Kuhlman SJ, Silver R, Le Sauter J, Bult-Ito A, McMahon DG
J Neurosci. 2003 23 (4): 1441-50

PMID: 12598633 · PMCID: PMC3281758

The endogenous circadian clock of the mammalian suprachiasmatic nucleus (SCN) can be reset by light to synchronize the biological clock of the brain with the external environment. This process involves induction of immediate-early genes such as the circadian clock gene Period1 (Per1) and results in a stable shift in the timing of behavioral and physiological rhythms on subsequent days. The mechanisms by which gene activation permanently alters the phase of clock neuron activity are unknown. To study the relationship between acute gene activation and persistent changes in the neurophysiology of SCN neurons, we recorded from SCN neurons marked with a dynamic green fluorescent protein (GFP) reporter of Per1 gene activity. Phase-resetting light pulses resulted in Per1 induction in a distinct subset of SCN neurons that also exhibited a persistent increase in action potential frequency 3-5 hr after a light pulse. By simultaneously quantifying Per1 gene activation and spike frequency in individual neurons, we found that the degree of Per1 induction was highly correlated with neuronal spike frequency on a cell-by-cell basis. Increased neuronal activity was mediated by membrane potential depolarization as a result of a reduction in outward potassium current. Double-label immunocytochemistry revealed that vasoactive intestinal peptide (VIP)-expressing cells, but not arginine vasopressin (AVP)-expressing cells, exhibited significant Per1 induction by light pulses. Rhythmic GFP expression occurred in both VIP and AVP neurons. Our results indicate that the steps that link acute molecular events to permanent changes in clock phase involve persistent suppression of potassium current, downstream of Per1 gene induction, in a specific subset of Per1-expressing neurons enriched for VIP.

MeSH Terms (26)

Action Potentials Animals Arginine Vasopressin Biological Clocks Cell Cycle Proteins Cells, Cultured Circadian Rhythm Electric Conductivity Gene Expression Regulation Green Fluorescent Proteins Kinetics Light Luminescent Proteins Male Membrane Potentials Mice Mice, Transgenic Models, Neurological Neurons Nuclear Proteins Patch-Clamp Techniques Period Circadian Proteins Potassium Channels Suprachiasmatic Nucleus Transcriptional Activation Vasoactive Intestinal Peptide

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