Dean M. Murakami

The retinohypothalamic tract in the cat: retinal ganglion cell morphology and pattern of projection

The pattern of retinal projection to the hypothalamus and the morphological properties of the retinal ganglion cells that comprise the retinohypothalamic tract have been examined in the cat. Intraocular injections of horseradish peroxidase revealed a dense retinal projection to the ventral suprachiasmatic nucleus; however, lighter projections were seen in the dorsal suprachiasmatic nucleus, and in hypothalamic regions both dorsal and lateral to the suprachiasmatic nucleus. Intrasuprachiasmatic nucleus injections of horseradish peroxidase retrogradely labelled retinal ganglion cells that were small to medium in soma size. The labelled ganglion cells exhibited long thin dendrites that were sparsely branched. The labelled retinal ganglion cells exhibited a significant change in soma size associated with retinal eccentricity. The morphological characteristics of the ganglion cells that project to the suprachiasmatic nucleus are similar to those of gamma cells.

Evidence for vestibular regulation of autonomic functions in a mouse genetic model

Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3b/Pou4f3). The only known phenotype of the Brn-3.1−/− mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1−/− mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1−/− mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

The retinohypothalamic projection and oxidative metabolism in the suprachiasmatic nucleus of primates and tree shrews

This study compared the patterns of retinal projections and oxidative metabolism in the hypothalamus of squirrel monkeys, Bonnet macaques, and tree shrews. Intraocular injections of horseradish peroxidase in primates demonstrated that retinal terminals were present from the anterior to posterior poles of the suprachiasmatic nucleus (SCN). The terminals were primarily located in the ventral and ventrolateral regions of the SCN. In addition, there was a relatively even density and distribution of retinal terminals between the ipsilateral and contralateral projections. The pattern of oxidative metabolism in the hypothalamus of the primates examined demonstrated that the SCN is highly metabolic relative to the surrounding area, and distinct regions of the SCN exhibit clear differences in metabolism. These distinct metabolic regions may reflect functional subdivisions within the SCN. In addition, elevated metabolism is found along the hypothalamo-optic chiasm border. The retinal projection to the hypothalamus in tree shrews was very different from that of the primates examined. The contralateral retinal projection was very dense, but the ipsilateral retinal projection was very sparse. Retinal terminals were primarily distributed along the lateral border of the SCN. Both the SCN and the region lateral to the SCN exhibited elevated oxidative metabolism relative to the surrounding hypothalamus.

Gravitational biology and the mammalian circadian timing system.

Mammals have evolved under the influence of many selective pressures. Two of these pressures have been the static force of gravity and the daily variations in the environment due to the rotation of the earth. It is now clear that each of these pressures has led to specific adaptations which influence how organisms respond to changes in either gravity or daily time cues. However, several unpredicted responses to altered gravitational environments occur within the homeostatic and circadian control systems. These results may be particularly relevant to biological and medical issues related to spaceflight. This paper demonstrates that the homeostatic regulation of rat body temperature, heart rate, and activity become depressed following exposure to a 2 G hyperdynamic field, and recovers within 5-6 days. In addition, the circadian rhythms of these same variables exhibit a depression of rhythm amplitude; however, recovery required a minimum of 7 days.

Influence of gravity on the circadian timing system

The circadian timing system (CTS) is responsible for daily temporal coordination of physiological and behavioral functions both internally and with the external environment. Experiments in altered gravitational environments have revealed changes in circadian rhythms of species ranging from fungi to primates. The altered gravitational environments examined included both the microgravity environment of spaceflight and hyperdynamic environments produced by centrifugation. Acute exposure to altered gravitational environments changed homeostatic parameters such as body temperature. These changes were time of day dependent. Exposure to gravitational alterations of relatively short duration produced changes in both the homeostatic level and the amplitude of circadian rhythms. Chronic exposure to a non-earth level of gravity resulted in changes in the period of the expressed rhythms as well as in the phase relationships between the rhythms and between the rhythms and the external environment. In addition, alterations in gravity appeared to act as a time cue for the CTS. Altered gravity also affected the sensitivity of the pacemaker to other aspects of the environment (i.e., light) and to shifts of time cues. Taken together, these studies lead to the conclusion that the CTS is indeed sensitive to gravity and its alterations. This finding has implications for both basic biology and space medicine.

Effects of square-wave and simulated natural light-dark cycles on hamster circadian rhythms

Circadian rhythms of activity (Act) and body temperature (Tb) were recorded from male Syrian hamsters under square-wave (LDSq) and simulated natural (LDSN, with dawn and dusk transitions) light-dark cycles. Light intensity and data sampling were under the synchronized control of a laboratory computer. Changes in reactive and predictive onsets and offsets for the circadian rhythms of Act and Tb were examined in both lighting conditions. The reactive Act onset occurred 1.1 h earlier ( P < 0.01) in LDSN than in LDSq and had a longer α-period (1.7 h; P < 0.05). The reactive Tb onset was 0.7 h earlier ( P < 0.01) in LDSN. In LDSN, the predictive Act onset advanced by 0.3 h ( P < 0.05), whereas the Tb predictive onset remained the same as in LDSq. The phase angle difference between Act and Tb predictive onsets decreased by 0.9 h ( P < 0.05) in LDSN, but the offsets of both measures remained unchanged. In this study, animals exhibited different circadian entrainment characteristics under LDSq and LDSN, suggesting that gradual and abrupt transitions between light and dark may provide different temporal cues.

The development of neurons in the cat perigeniculate nucleus and reticular nucleus of the thalamus.

The postnatal development of soma size and cytochrome oxidase activity was examined in the perigeniculate nucleus (PGN) and reticular nucleus of the thalamus (RNT). Neurons in the PGN and RNT exhibited a rapid increase in soma size between 2 and 4 weeks of age. During this period of cell growth there is an increase in the intensity of cytochrome oxidase staining within the cell body. Cells in both the PGN and RNT decrease in size after 4 weeks of age, and become very fusiform in shape. During this postnatal period, there is also a shift in cytochrome oxidase staining from the cell body to the dendrites.

The development of soma size changes in the C-laminae of the cat lateral geniculate nucleus following monocular deprivation

This study examined the pattern of soma size changes in the cat dorsal lateral geniculate nucleus (dLGN) from 4 weeks of age to adulthood following monocular lid suture at two weeks of age. Different patterns of soma size changes were found between the A-laminae and C-laminae. In layers A, A1, and C significant soma size differences were found between the deprived and non-deprived laminae by 4 weeks of age. However, the magnocellular portion of layer C was affected more by deprivation than the parvocellular portion. Layer C1 did not reveal significant soma size changes until 20 weeks of age. Layer C2 did not exhibit any soma size changes at any age. These differential responses to monocular deprivation suggest different time courses of development among the dLGN laminae.

Characteristics of Nasal and Temporal Retina in Siamese and Normally Pigmented Cats; pp. 91–102

Properties of ganglion cells in nasal and temporal retina of Siamese and normally-pigmented cats are described. In agreement with earlier reports on normal cats, the somas of both X and Y cells are la