Evidence for macular gravity receptor modulation of hypothalamic, limbic and autonomic nuclei.

Mice lacking normal vestibular gravity reception show altered homeostatic, circadian and autonomic responses to hypergravity (+G) exposure. Using c-Fos as a marker of neuronal activation, the current study identifies CNS nuclei that may be critical for initiating and integrating such responses to changes in vestibular signaling. This experiment utilized the mutant C57BL/6JEi-het mouse (het), which lacks macular otoconia and thus gravity receptor function. Following 2 h of 2G (2x Earth's gravity) exposure (via centrifugation) the neuronal responses of the het mice were compared with wildtype mice similarly exposed to 2G, as well as het and wildtype 1G controls. Wildtype mice exposed to 2G demonstrated robust c-Fos expression in multiple autonomic, hypothalamic and limbic nuclei, including: the lateral septum, bed nucleus of the stria terminalis, amygdala, paraventricular hypothalamus, dorsomedial hypothalamus, arcuate, suprachiasmatic hypothalamus, intergeniculate leaflet, dorsal raphe, parabrachial and locus coeruleus. The het mice exposed to 2G demonstrated little to null c-Fos expression in these nuclei with a few exceptions and, in general, a similar pattern of c-Fos to 1G controls. Data from this study further support the existence of a complex and extensive influence of the neurovestibular system on homeostatic, circadian and possibly autonomic regulatory systems.

Chronic 2G exposure affects c-Fos reactivity to a light pulse within the rat suprachiasmatic nucleus.

This study examined the effect of the hyperdynamic environment on the function of the retinohypothalamic tract. Rats were exposed to either 2 days or 21 days of 2G via centrifugation. During the last hour of 2G exposure, one series of rats was exposed to a 1 hour phase-shifting light pulse while the second series of rats did not receive a light pulse. In addition a groups of 1G controls was exposed to the same 1 hour lighting paradigm. All animals were processed for c-Fos within the SCN. The 1G controls showed the normal response to light in which significantly greater numbers of c-Fos positive neurons were found in the SCN of the light pulsed rats relative to that of the nonlight pulsed rats. However, rats exposed to 2 days of 2G did not show the same response to light. Light pulsed rats and nonlight pulsed rats exhibited few c-Fos positive neurons within the SCN. A recovery in the effect of light to induce c-Fos reactivity within SCN neurons occurred in the rats exposed to 21 days of 2G. These results suggest that exposure to 2G can temporarily suppress the responsiveness of the SCN to the phase-shifting effects of light mediated by the retinohypothalamic tract.

Diurnal responses of mammals to acute exposure to a hyperdynamic environment.

Acute exposure to hyperdynamic environments elicits significant depressions in core temperature in both diurnal squirrel monkeys and nocturnal rats. This study describes time of day variations in core temperature responses in squirrel monkeys and rats exposed for 70 min to a hyperdynamic environment (2 g) produced via centrifugation. Experiments were performed during the middle of the light or dark phase. After a 70-min control period, squirrel monkey resting core temperature was 38.6 +/- 0.2 (SE) and 36.8 +/- 0.2 degrees C during the day and night, respectively. At the end of a 7-min exposure to 2 g, squirrel monkey core temperature decreased 1.3 +/- 0.2 degree C during the day but remained a constant 36.8 +/- 0.4 degrees C at night. Core temperature of rats exposed to an identical 70-min 2 g profile decreased 1.5 +/- 0.4 degree C from a resting 37.1 +/- 0.6 degrees C during the day and 2.3 +/- 0.2 degrees C from a resting 37.8 +/- 0.3 degrees C at night. Thus, in both species, there were clear day-night differences in response to hyperdynamic environments, with the greatest fall in core temperature occurring during the animal's active period.

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.

Circadian brain and body temperature rhythms in the squirrel monkey.

This study examines the hypothalamic temperature rhythm and its relationship with the colonic temperature rhythm of squirrel monkeys in 24-h light-dark cycles (LD 12:12) at four different ambient temperatures (Ta). The waveforms and phases of both temperature rhythms were similar in all TaS. The rhythm amplitudes were, however, reduced as Ta increased. The 24-h means also showed systematic decreases at higher TaS. The hypothalamic temperature was regulated over a narrower range than the colonic temperature and was higher than colonic temperature at all TaS except the warmest. Further, the mean nighttime temperatures were influenced more by Ta than were the mean daytime temperatures. In summary, the hypothalamic and colonic temperature rhythms are very similar in their circadian regulation. However, the mean temperature levels of these rhythms are controlled differentially. Thus these rhythms are the integrated response of both the circadian and thermoregulatory control systems.

Circadian rhythm of body temperature persists after suprachiasmatic lesions in the squirrel monkey.

Squirrel monkeys (Saimiri sciureus) demonstrate prominent circadian (approx 24 h) rhythms in many behavioral and physiological variables including drinking and body temperature. Both of these rhythms can be entrained by a 24-h light-dark cycle (LD 12:12) but will free-run with an endogenous period in a constantly illuminated (LL:600 lx) environment free of time cues. After radio-frequency lesions were placed stereotaxically in the suprachiasmatic nuclei (SCN) of five monkeys, the circadian rhythm of drinking behavior was disrupted when the monkeys were maintained in LL. However, the circadian rhythm in core body temperature in these animals persisted in LL with a significant circadian spectral component following destruction of the SCN. The SCN thus appear to be of fundamental importance for regulating the circadian organization of drinking; however, an oscillator located elsewhere in the squirrel monkey is capable of generating the core body temperature rhythm.

Spinal cord thermosensitivity and sorting of neural signals in cold-exposed rats.

In the present study, data relevant to the presence or absence of sorting of neural signals were obtained by evaluating the thermal responses to spinal warming in the chronically prepared rat. Specifically, shivering activity and the rate of oxygen consumption (VO2) were measured in unanesthetized rats during cold exposure (10-16 degrees C). Warming the spinal cord at the level of T2 resulted in a significant decrease in shivering (P less than 0.001), without a significant change in VO2. The shivering response was reversed upon cessation of heating. These results are interpreted as indicating a direct influence of spinal cord temperature on shivering but not nonshivering thermogenesis in the rat. Similarly, in previous work with the rat, we have obtained data supporting hypothalamic receptor control of nonshivering but not shivering heat production. These findings are thus consistent with the suggestion that in the rat there occurs a sorting of neural signals. That is, impulses from the three thermoreceptor locations are not integrated in an identical manner for the control of shivering and nonshivering thermogenesis.

Sorting of signals from thermosensitive areas.

Of the several models proposed for the neural regulation of temperature in cold-exposed animals, two have been previously restated in dynamic form using CSMP. Subsequently, computer simulations have led to the design and execution of experiments for selection of the more appropriate model for cold-exposed rats. These experiments, as described in the present paper, have been interpreted as being consistent with the model which sorts signals from thermosensitive areas and channels the selected signals over separate neural pathways to independently control each mode of heat production. Since this model requires multiplication of neural signals, possible neuronal mechanisms which may underline such multiplication are discussed. In addition, parameter variation to account for febril responses and rate sensitivity have been evaluated.

Shivering and nonshivering thermogenic responses of cold-exposed rats to hypothalamic warming.

The concurrent neural control of two thermoregulatory responses, shivering thermogenesis (ST) and nonshivering thermogenesis (NST), was investigated in chronically implanted cold-exposed rats. The effects of heating the preoptic/anterior hypothalamus (POAH) on shivering and on the rate of oxygen consumption (Vo2) were measured in these unanesthetized animals. With ambient temperature maintained constant (at some value between 10 and 16 degrees C), warming the hypothalamus 2-3 degrees C resulted in a significant decrease in Vo2 (Psmaller than 0.001) and an increase in shivering (Psmaller than .01), these responses being reversed on cessation of hypothalamic warming. These results are consistent with the proposal that, in the cold-exposed animal, elevated POAH temperatures directly inhibit NST even though shivering may increase (possibly as a compensation for the decrease in nonshivering heat production). They also rule out the possibility that, in the rat, signals from cutaneous and hypothalamic thermoreceptors are integrated in an indentical manner by the neural controllers for ST and NST.