Multiple hypothalamic cell populations encoding distinct visual information

Non-technical summary A retinal projection to a brain 'clock' in the suprachiasmatic nuclei (SCN) and various other hypothalamic regions allows light to regulate many aspects of physiology and behaviour. The exact nature of light-evoked responses in these hypothalamic regions and the degree to which they rely upon the various classes of retinal photoreceptor is incompletely understood. Multielectrode recordings in the mouse hypothalamus reveal four classes of visually responsive neuron whose activity is altered by changes in illumination (contrast) and/or according to steady-state light levels (irradiance). These cells appear in different locations and vary in their daily profile of electrical activity. The properties of one class suggest a direct association with regulating the SCN clock, while the others appear suited to provide more direct modulations in physiology and behaviour. Together, these findings establish a framework for understanding how light regulates such a diverse array of body systems.Environmental illumination profoundly influences mammalian physiology and behaviour through actions on a master circadian oscillator in the suprachiasmatic nuclei (SCN) and other hypothalamic nuclei. The retinal and central mechanisms that shape daily patterns of light-evoked and spontaneous activity in this network of hypothalamic cells are still largely unclear. Similarly, the exact nature of the sensory information conveyed by such cells is unresolved. Here we set out to address these issues, through multielectrode recordings from the hypothalamus of red cone knockin mice (Opn1mwR). With this powerful mouse model, the photoreceptive origins of any response can be readily identified on the basis of their relative sensitivity to short and long wavelength light. Our experiments revealed that the firing pattern of many hypothalamic cells was influenced by changes in light levels and/or according to the steady state level of illumination. These 'contrast' and 'irradiance' responses were driven primarily by cone and melanopsin photoreceptors respectively, with rods exhibiting a much more subtle influence. Individual hypothalamic neurons differentially sampled from these information streams, giving rise to four distinct response types. The most common response phenotype in the SCN itself was sustained activation. Cells with this behaviour responded to all three photoreceptor classes in a manner consistent with their distinct contributions to circadian photoentrainment. These 'sustained' cells were also unique in our sample in expressing circadian firing patterns with highest activity during the mid projected day. Surprisingly, we also found a minority of SCN neurons that lacked the melanopsin-derived irradiance signal and responded only to light transitions, allowing for the possibility that rod-cone contrast signals may be routed to SCN output targets without influencing neighbouring circadian oscillators. Finally, an array of cells extending throughout the periventricular hypothalamus and ventral thalamus were excited or inhibited solely according to the activity of melanopsin. These cells appeared to convey a filtered version of the visual signal, suitable for modulating physiology/behaviour purely according to environmental irradiance. In summary, these findings reveal unexpectedly widespread hypothalamic cell populations encoding distinct qualities of visual information.