Experience-Independent Development of the Hamster Circadian Visual System

Experience-dependent functional plasticity is a hallmark of the primary visual system, but it is not known if analogous mechanisms govern development of the circadian visual system. Here we investigated molecular, anatomical, and behavioral consequences of complete monocular light deprivation during extended intervals of postnatal development in Syrian hamsters. Hamsters were raised in constant darkness and opaque contact lenses were applied shortly after eye opening and prior to the introduction of a light-dark cycle. In adulthood, previously-occluded eyes were challenged with visual stimuli. Whereas image-formation and motion-detection were markedly impaired by monocular occlusion, neither entrainment to a light-dark cycle, nor phase-resetting responses to shifts in the light-dark cycle were affected by prior monocular deprivation. Cholera toxin-b subunit fluorescent tract-tracing revealed that in monocularly-deprived hamsters the density of fibers projecting from the retina to the suprachiasmatic nucleus (SCN) was comparable regardless of whether such fibers originated from occluded or exposed eyes. In addition, long-term monocular deprivation did not attenuate light-induced c-Fos expression in the SCN. Thus, in contrast to the thalamocortical projections of the primary visual system, retinohypothalamic projections terminating in the SCN develop into normal adult patterns and mediate circadian responses to light largely independent of light experience during development. The data identify a categorical difference in the requirement for light input during postnatal development between circadian and non-circadian visual systems

Experience-Independent Development of the Hamster Circadian Visual System

Experience-dependent functional plasticity is a hallmark of the primary visual system, but it is not known if analogous mechanisms govern development of the circadian visual system. Here we investigated molecular, anatomical, and behavioral consequences of complete monocular light deprivation during extended intervals of postnatal development in Syrian hamsters. Hamsters were raised in constant darkness and opaque contact lenses were applied shortly after eye opening and prior to the introduction of a light-dark cycle. In adulthood, previously-occluded eyes were challenged with visual stimuli. Whereas image-formation and motion-detection were markedly impaired by monocular occlusion, neither entrainment to a light-dark cycle, nor phase-resetting responses to shifts in the light-dark cycle were affected by prior monocular deprivation. Cholera toxin-b subunit fluorescent tract-tracing revealed that in monocularly-deprived hamsters the density of fibers projecting from the retina to the suprachiasmatic nucleus (SCN) was comparable regardless of whether such fibers originated from occluded or exposed eyes. In addition, long-term monocular deprivation did not attenuate light-induced c-Fos expression in the SCN. Thus, in contrast to the thalamocortical projections of the primary visual system, retinohypothalamic projections terminating in the SCN develop into normal adult patterns and mediate circadian responses to light largely independent of light experience during development. The data identify a categorical difference in the requirement for light input during postnatal development between circadian and non-circadian visual systems.</p

Melatonin Acts at the Suprachiasmatic Nucleus to Attenuate Behavioral Symptoms of Infection

In common with reproduction, immune function exhibits strong seasonal patterns, which are driven by annual changes in day length (photoperiod) and melatonin secretion. Whereas changes in melatonin communicate seasonal time into the reproductive axis via subcortical receptors, the relevant melatonin targets for communicating seasonal time into the immune system remain unspecified. The authors report that melatonin implants targeting the hypothalamic suprachiasmatic nuclei (SCN) induced a winter phenotype in the immune system. SCN melatonin implants attenuated infection-induced anorexia and cachexia, indicating that the SCN mediate the effects of melatonin on these behavioral and metabolic symptoms of infection. However, SCN melatonin implants failed to induce winter-like peripheral leukocyte concentrations or behavioral thermoregulatory responses to infection. In contrast, subcutaneous melatonin implants induced winter-like changes in all behavioral and immunological parameters. Melatonin acts directly at the SCN to induce seasonal changes in neural-immune systems that regulate behavior. The data identify anatomical overlap between neural substrates mediating the effects of melatonin on the reproductive and immune systems but also suggest that the SCN are not the sole mediator of photoperiodic effects of melatonin on immunity. © 2007 American Psychological Association

Light-induced c-<i>fos</i> expression in the SCN.

<p><b><i>A</i></b> Representative images of DAB-labeled Fos-IR cells in SCN coronal sections from 2 Syrian hamsters. <b><i>B</i></b> Mean (± s.e.m.) number of c-Fos immunoreactive (IR) cells in both SCN 90 minutes after the delivery of a dark pulse (DP) or a light pulse (LP) at CT19 (see methods for details) to an eye that had been either exposed or occluded from weeks 1–10 and from weeks 11–38. * p<0.0001 vs. all other groups.</p

Occlusion of circadian light perception.

<p>Representative double-plotted locomotor activity records of Syrian hamsters in experiment 1. Clock time is indicated on the horizontal axis along the top of each actogram. Lights on/off are indicated by light and shaded areas of the actogram. Hamsters were blinded in the left eye via optic nerve transection (indicated by *), transferred to DD, and subjected at ZT19 to <b><i>A</i></b> a control dark pulse (DP) with a clear lens over the right eye (CR), <b><i>B</i></b> a 15 min light pulse (LP) with an occluder over the right eye (BR), or <b><i>C</i></b> a 15 min LP with a clear lens over the intact eye. <b><i>D</i></b> Mean (± s.e.m.) magnitude of the phase shift in activity onset as measured 5 days later. * p<0.001 vs. all other groups.</p

Representative double-plotted locomotor activity records of Syrian hamsters in experiment 5.

<p>Clock time is indicated on the horizontal axis along the top of each actogram. Lights on/off are indicated by light and shaded areas of the actogram. Hamsters were subjected to the following occlusion treatments for 38 weeks: <b><i>A</i></b> a clear lens over the right eye (CR), <b><i>B</i></b> an occluder over the right eye (BR), <b><i>C</i></b> an occluder over the left eye (BL), or <b><i>D</i></b> occluders over both eyes (BB).</p

Light-induced phase shifts of the circadian locomotor activity rhythm after occluder reassignment.

<p><b><i>A</i></b>–<b><i>D</i></b> Representative double-plotted locomotor activity records of Syrian hamsters bearing: <b><i>A</i></b> occluders in both eyes (BB→BB), <b><i>B</i></b> an occluder in the right eye (BR→BR), <b><i>C</i></b> an occluder that was moved from the right eye to the left on week 10 (BR→BL), and <b><i>D</i></b> a clear lens in the right eye (CR→CR). Clock time is indicated on the horizontal axis along the top of each actogram. Lights on/off are indicated by light and shaded areas of the actogram. <b><i>E</i></b> Mean (± s.e.m.) daily locomotor activity onsets of hamsters bearing ocular occluders during the 3 weeks immediately following a 5-hour phase advance of the light-dark cycle. * p<0.05 vs. all other groups, # p<0.05 vs. the CR-CR group.</p