Figure 7.

Proposed regulation of the phase of the circadian clock and Period (Per) gene expression in the SCN by GABA_A receptor activation and inactivation. Left Panel: As described in Figure 6, light results in glutamate release from the retinohypothalamic tract (RHT). In response, there is a sustained release of GABA from, as well as a sustained induction of Per in, non-rhythmic neurons. In response, there is a sustained activation of GABA_A receptors and a sustained induction of Per in rhythmic neurons resulting in a phase delay of the circadian clock. Middle Panel: Acute activation of GABA_A receptors by injection of muscimol prior to a light pulse inhibits light induction of the sustained release of GABA from, as well as an inhibition of Per induction in, non-rhythmic neurons. Acute activation of GABA_A receptors inhibits NMDA-induced phase delays suggesting that activation of GABA_A receptors does not inhibit light-induced phase delays solely by inhibiting light-induced glutamate release (Mintz et al., 2002). Acute activation of GABA_A receptors ultimately blocks light-induced phase delays by preventing Per induction in rhythmic neurons. Right Panel: Sustained inhibition of GABA_A receptors by at least six hourly injections of bicuculline following a light pulse blocks light-induced phase delays by inhibiting Per induction in rhythmic neurons.