Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
Central Animal Facility, Leiden University Medical Center, Leiden, The Netherlands.
FASEB J. 2022 Aug;36(8):e22415. doi: 10.1096/fj.202200477R.
In both diurnal and nocturnal mammals, the timing of activity is regulated by the central circadian clock of the suprachiasmatic nucleus (SCN). The SCN is synchronized to the external light cycle via the retinohypothalamic tract (RHT). To investigate potential differences in light processing between nocturnal mice and the diurnal rodent Rhabdomys pumilio, we mimicked retinal input by stimulation of the RHT ex vivo. Using Ca imaging, we observed excitations as well as inhibitions of SCN neurons in response to electrical RHT stimulation. In mice, the vast majority of responses were excitatory (85%), whereas in Rhabdomys, the proportion of excitatory and inhibitory responses was similar (51% excitatory, 49% inhibitory). Glutamate blockers AP5 and CNQX blocked the excitatory responses to RHT stimulation but did not abolish the inhibitory responses in mice or Rhabdomys, indicating that the inhibitions were monosynaptically transmitted via the RHT. Simultaneous application of glutamate blockers with the GABA antagonist gabazine blocked all inhibitory responses in mice, but not in Rhabdomys. Collectively, our results indicate that in Rhabdomys, considerably more inhibitory responses to light are present and that these responses are driven directly by the RHT. We propose that this increased proportion of inhibitory input could reflect a difference in the entrainment mechanism employed by diurnal rodents.
在昼夜活动的哺乳动物中，活动的时间由视交叉上核（SCN）的中枢生物钟调节。SCN 通过视网膜下丘脑束（RHT）与外部光周期同步。为了研究夜间活动的小鼠和昼行性啮齿动物多瘤鼠（Rhabdomys pumilio）之间在光处理方面的潜在差异，我们通过离体刺激 RHT 来模拟视网膜输入。使用钙成像，我们观察到 SCN 神经元对 RHT 电刺激的兴奋和抑制反应。在小鼠中，绝大多数反应为兴奋（85%），而在多瘤鼠中，兴奋和抑制反应的比例相似（兴奋 51%，抑制 49%）。谷氨酸阻断剂 AP5 和 CNQX 阻断了 RHT 刺激的兴奋反应，但没有消除小鼠或多瘤鼠中的抑制反应，表明抑制反应是通过 RHT 单突触传递的。同时应用谷氨酸阻断剂和 GABA 拮抗剂gabazine 阻断了小鼠的所有抑制反应，但在多瘤鼠中没有阻断。总之，我们的结果表明，多瘤鼠中存在更多的对光的抑制反应，这些反应是由 RHT 直接驱动的。我们提出，这种抑制性输入比例的增加可能反映了昼行性啮齿动物采用的不同的驯化机制。
