Melanopsin: From a small molecule to brain functions.

Melanopsin, a G family coupled receptor, found within the ganglion cell layer in the retina, plays an important role in non-image-forming visual functions, including hormone secretion, entrainment of circadian rhythms, cognitive and affective processes. Diffuse projections of melanopsin-containing cells to many brain areas suggest that different responses may involve different neural projections, thus different melanopsin cells. Considering the complexity of the melanopsin system, its contribution to so many different biological functions is not surprising. In this review, we summarize the current knowledge about melanopsin in terms of its photophysics, photochemistry, mechanisms of activation, cell signaling, morphology, and physiology. In the last part, the role of melanopsin in image and non-image forming processes and cognitive and affective functioning of animals and humans, are discussed. Although in recent years considerable insight has been gained into the melanopsin system, it still remains an open question of how one protein expressed by several thousand cells in the retina, could be responsible for so many diverse functions and what activation mechanism(s) it uses.

Neuronal Responses to Short Wavelength Light Deficiency in the Rat Subcortical Visual System.

The amount and spectral composition of light changes considerably during the day, with dawn and dusk being the most crucial moments when light is within the mesopic range and short wavelength enriched. It was recently shown that animals use both cues to adjust their internal circadian clock, thereby their behavior and physiology, with the solar cycle. The role of blue light in circadian processes and neuronal responses is well established, however, an unanswered question remains: how do changes in the spectral composition of light (short wavelengths blocking) influence neuronal activity? In this study we addressed this question by performing electrophysiological recordings in image (dorsal lateral geniculate nucleus; dLGN) and non-image (the olivary pretectal nucleus; OPN, the suprachiasmatic nucleus; SCN) visual structures to determine neuronal responses to spectrally varied light stimuli. We found that removing short-wavelength from the polychromatic light (cut off at 525 nm) attenuates the most transient ON and sustained cells in the dLGN and OPN, respectively. Moreover, we compared the ability of different types of sustained OPN neurons (either changing or not their response profile to filtered polychromatic light) to irradiance coding, and show that both groups achieve it with equal efficacy. On the other hand, even very dim monochromatic UV light (360 nm; log 9.95 photons/cm2/s) evokes neuronal responses in the dLGN and SCN. To our knowledge, this is the first electrophysiological experiment supporting previous behavioral findings showing visual and circadian functions disruptions under short wavelength blocking environment. The current results confirm that neuronal activity in response to polychromatic light in retinorecipient structures is affected by removing short wavelengths, however, with type and structure - specific action. Moreover, they show that rats are sensitive to even very dim UV light.

Orexin A as a modulator of dorsal lateral geniculate neuronal activity: a comprehensive electrophysiological study on adult rats.

Orexins (OXA, OXB) are hypothalamic peptides playing crucial roles in arousal, feeding, social and reward-related behaviours. A recent study on juvenile rats suggested their involvement in vision modulation due to their direct action on dorsal lateral geniculate (dLGN) neurons. The present study aimed to verify whether a similar action of OXA can be observed in adulthood. Thus, in vivo and in vitro electrophysiological recordings on adult Wistar rats across light-dark and cortical cycles were conducted under urethane anaesthesia. OXA influenced ~28% of dLGN neurons recorded in vivo by either excitation or suppression of neuronal firing. OXA-responsive neurons did not show any spatial distribution nor represent a coherent group of dLGN cells, and responded to OXA similarly across the light-dark cycle. Interestingly, some OXA-responsive neurons worked in a cortical state-dependent manner, especially during the dark phase, and 'preferred' cortical activation over slow-wave activity induced by urethane. The corresponding patch clamp study confirmed these results by showing that < 20% of dLGN neurons were excited by OXA under both light regimes. The results suggest that OXA is involved in the development of the visual system rather than in visual processes and further implicate OXA in the mediation of circadian and arousal-related activity.

Modulation of Spontaneous and Light-Induced Activity in the Rat Dorsal Lateral Geniculate Nucleus by General Brain State Alterations under Urethane Anesthesia.

The thalamic dorsal lateral geniculate nucleus (dLGN) serves as a gating station for the transfer of light information en route to the primary visual cortex (V1). Although the modulatory input arising from the V1 and several brainstem nuclei to the dLGN is well characterised in higher mammals, little is known about its influence on dLGN activity in rodents. Using simultaneous recordings of electrocorticogram (ECoG) and single unit neuronal activity under urethane anesthesia in Long Evans rats, we managed to show that cyclic changes in the general brain state strongly affect spontaneous activity and light encoding properties of dLGN neurons. First, we characterised several groups of dLGN cells: neurons led by ECoG, neurons in which the spike rate preceded ECoG changes and neurons co-occurring or not correlated with ECoG signal. Secondly, we verified that although the general light responsiveness of the dLGN is not influenced by the state of the brain, modulation of types of photoresponses and differences in ability to encode ambient light levels were observed. Cells responding to light in a sustained manner encoded light intensity more accurately during the cortical activation phase of urethane anesthesia. On the other hand, isoflurane anesthesia does not induce such rhythmic changes in ECoG and shuts down the spontaneous neuronal activity in the dLGN. Together, these data suggest a greater modulation of spontaneous activity and dLGN neurons function, than it was previously reported for the rodent dLGN and highlight the role of anesthesia in interpretations of findings from ongoing acute experiments.