GABA_A receptor agonist muscimol can reset the phase of neural activity rhythm in the rat suprachiasmatic nucleus in vitro

We investigated the phase-resetting effect of muscimol, γ-amino butyric acid (GABA)_A receptor agonist, on the circadian neural activity rhythm of the rat suprachiasmatic nucleus (SCN), which contains a circadian pacemaker. Acute application of muscimol inhibited the neural activity of the SCN in a dose-dependent manner. Under the tissue culture condition, the treatment with 10 μM muscimol during the early- to mid-subjective day on the first day (day 1) in vitro produced the largest phase advance in neural activity rhythm of the SCN on day 2. By contrast, the administration of muscimol during the subjective night produced no change. These phase changes were similar to those reported for dark pulses in constant light. These findings indicate that muscimol can directly affect SCN neurons and reset the circadian pacemaker in the SCN. The GABA neural function through the activation of GABA_A receptors may play a role in modulating the phase of the SCN clock, especially during the subjective day.