Fos immunoreactivity in rat subcortical visual shell in response to illuminance changes.

Immediate early gene expression has been used frequently as a marker of activity in the circadian visual system. Recent evidence suggests that the pretectum participates in orchestrating sleep and circadian responses to light. Lesions of the pretectum eliminate dark shift-induced rapid eye movement sleep triggering in albino rats, and compromise circadian phase shifts in hamsters. We hypothesized that regions of the pretectum respond to light with robust and region-specific Fos activation, similar to the suprachiasmatic nucleus and intergeniculate leaflet. We used Fos expression, the protein product of the immediate early gene c-fos, as a functional marker to measure the responses of neurons following acute lighting changes. Rats maintained on a 12:12 light-dark cycle were subjected to a shift from light-to-dark or from dark-to-light at midday (Zeitgeber time 6) or midnight (Zeitgeber time 18). Fos expression was visualized with immunocytochemistry and quantified with an automated scoring system. We found three regions in the pretectum (the olivary pretectal nucleus, posterior limitans, and a region homologous to the hamster commissural pretectal nucleus), and two regions in the lateral geniculate complex (the intergeniculate leaflet and ventral lateral geniculate nucleus) that demonstrated significant Fos activation in response to light. Furthermore, the olivary pretectal nucleus, the posterior limitans, and the ventral lateral geniculate nucleus showed preferential Fos activation after acute light onset rather than following chronic exposure to light at midday, whereas at midnight these nuclei showed Fos activation following both chronic light exposure and acute light onset. Given the extensive anatomical connections between pretectal nuclei and other nuclei in the subcortical visual shell, as well as with centers for sleep and arousal, it is highly plausible that these pretectal nuclei integrate information about changes in illuminance, and aid in the coordination of acute behavioral responses to light.

Vestibulo-ocular pathways modulate extraocular muscle myosin expression patterns.

The genetic and epigenetic influences that establish and maintain the unique phenotype of the extraocular muscles (EOMs) are poorly understood. The vestibulo-ocular reflex (VOR) represents an important input into the EOMs, as it stabilizes eye position relative to the environment and provides a platform for function of all other eye movement systems. A role for vestibular cues in shaping EOM maturation was assessed in these studies using the ototoxic nitrile compound 3',3'-iminodipropionitrile (IDPN) to eliminate the receptor hair cells that drive the vestibulo-ocular reflex. Intraperitoneal injections of IDPN were followed by a 2-week survival period, after which myosin heavy chain (MyHC) analysis of the EOMs was performed. When IDPN was administered to juvenile rats, the proportion of eye muscle fibers expressing developmental and fast myosins was increased, while EOM-specific MyHC mRNA levels were downregulated. By contrast, IDPN treatment in adult rats affected only the proportion of fibers expressing developmental MyHC isoforms, leaving the EOM-specific MyHC mRNA unaltered. These data provide evidence that the VOR modulates EOM-specific MyHC expression in development. The lack of significant changes in EOM-specific MyHC expression in adult EOM following IDPN administration suggests that there may be a critical period during development when alterations in vestibular activity have significant and permanent consequences for the eye muscles.