Abstract

Mammalian circadian rhythms are generated and regulated by a pacemaker located in the suprachiasmatic nucleus (SCN) in the hypothalamus. Transmission of photic information to the SCN occurs via a direct projection from the retina, the retinohypothalamic tract, and an indirect projection from the retinorecipient intergeniculate leaflet (IGL), the geniculohypothalamic tract. The retinohypothalamic tract is necessary for synchronization of rhythms to environmental light-dark cycles. In contrast, although the IGL is strategically located to convey light information to the SCN, a role for the IGL in photic entrainment has not been established. IGL-lesioned hamsters have been shown to entrain normally to light-dark cycles; effects of the lesion have been manifested in slower rates of re-entrainment to shifts in the light-dark cycle and small changes in the size of light-induced phase shifts. In the present thesis, the relationship between the IGL and the circadian response to light is explored in two sets of experiments. The first three experiments evaluated activation of IGL neurons by light using immunohistochemical expression of Fos protein as a marker of cellular activation. In rodents, light-induced Fos in SCN neurons is phase dependent and is correlated with the effectiveness of such light to phase shift circadian rhythms. Furthermore, because the IGL has been implicated in the effects of nonphotic stimuli on circadian rhythms, the induction of Fos in the SCN and IGL in response to nonphotic manipulations was assessed. Results demonstrate that, in contrast to light-induced Fos in the SCN, light induces Fos protein in the IGL regardless of circadian time, and continues to do so as long as the animal is exposed to light. Moreover, nonphotic manipulations induce Fos in both SCN and IGL. However, in the IGL, Fos expression in response to such treatments was enhanced during the light phase of the light-dark cycle. Pharmacological manipulations that attenuate both light-induced phase shift and Fos expression in the SCN are without effect on light-induced Fos expression in the IGL. The effects of electrolytic lesions of the IGL on circadian temperature rhythms were examined under different lighting schedules in the final two experiments using a telemetry system. Rhythms in these animals were compared to those of intact controls as well as to rhythms of rats with neurotoxic damage to the visual system resulting from neonatal monosodium. glutamate (MSG) treatment. IGL-lesioned rats entrained normally to light-dark cycles consisting of 12 hours of light followed by 12 hours of darkness, and showed the disruption of rhythmicity after prolonged constant light housing seen in intact animals. However, in contrast to intact and MSG-treated rats, IGL-lesioned animals exhibited free-running temperature rhythms under a skeleton photoperiod consisting of one-hour of light exposure at times corresponding to dusk and dawn. Because nocturnal animals normally experience light only around dusk and dawn, the inability to entrain to this ecologically relevant lighting schedule suggests that the IGL plays a critical role in photic entrainment.