Inputs and Outputs of the Mammalian Circadian Clock

Simple Summary In mammals, circadian rhythms in nearly all behaviors and physiological processes are controlled by the suprachiasmatic nucleus, a collection of neurons in the hypothalamus that synchronize the brain and body to local time. However, the circuits linking the suprachiasmatic nucleus to both the external world and to downstream targets are poorly understood. This review describes the inputs to and outputs from the suprachiasmatic nucleus. A better understanding of the circadian "connectome" is essential to determine how the disruption of these circuits can negatively impact human health. Circadian rhythms in mammals are coordinated by the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Light and other environmental inputs change the timing of the SCN neural network oscillator, which, in turn, sends output signals that entrain daily behavioral and physiological rhythms. While much is known about the molecular, neuronal, and network properties of the SCN itself, the circuits linking the outside world to the SCN and the SCN to rhythmic outputs are understudied. In this article, we review our current understanding of the synaptic and non-synaptic inputs onto and outputs from the SCN. We propose that a more complete description of SCN connectivity is needed to better explain how rhythms in nearly all behaviors and physiological processes are generated and to determine how, mechanistically, these rhythms are disrupted by disease or lifestyle.