Interactions Between DPAT ad Optic Chiasm Stimulation in Resetting Circadian Clock Phase

All organisms exhibit daily rhythms in behavior and physiology controlled by endogenous circadian, or near 24 h, clocks. In mammals, the circadian clock is in a brain area called the suprachiasmatic nucleus (SeN). Neuronal activity in the SeN exhibits a 24-h pattern that peaks in the day. The circadian clock, located in the SeN, receives modulatory input from other areas of the brain including serotonergic input from the raphe nucleus and glutametergic input via the retinohypothalamic tract. Interactions between these two inputs and their effect on circadian phase were examined using DPAT, a 5-HT1A/7 agonist, and optic chiasm stimulation.

For these experiments, we prepared brain slices containing the SeN from rats and placed them in a support chamber. Experimental manipulations were applied to the slices for 10-30 min on day 1 in vitro, and neuronal activity recorded on day 2. Under these conditions SeN neuronal activity normally peaks at Zeitgeber time (ZT) 5.81 ±0.1 0 (n=5; where ZT 0 is lights-on and ZT 12 is lights-off in the animal colony). At ZT 19, the optic chiasm was stimulated, which releases glutamate onto the SeN via its natural pathway. This treatment advances the SeN clock (peak time = ZT 2.88±0.43, n=4). DPAT application during DeS appears to partially, but not completely, block the advance (peak time = ZT 3.8±0.5, n=5). These results suggest that 5-HT may modulate phase advances induced by DeS at ZT 19.