Fos and FRA protein expression in rat precerebellar structures during the Neurolab Space Mission

Changes in gene expression were examined in precerebellar structures during and after space flight. These structures included the inferior olive (IO), the source of climbing fibers, and the lateral reticular nucleus (LRt) and basilar pontine nuclei (PN), sources of mossy fibers. We examined two immediate early gene products with two different time courses of expression: Fos, which persists only for a few (6-8)h after activation and FRA expression, which lasts for longer periods of time, i.e. hours and/or days after activation.Gravity effects on Fos and FRA gene expression were evident in vestibular and visual areas of the IO, including the dorsomedial cell column, the beta subnucleus and the dorsal cap of Kooy of the medial nucleus (which projects to the flocculonodular lobe, i.e. to the vestibular area of the IO involved in the olivary control of the vestibulo-ocular reflex (VOR)). Gene expression also affected the subnuclei A, B, and C and the caudal part of the medial IO. These olivary regions do not receive vestibular afferents, but rather spinal afferents, and are particularly involved in the olivary control of the vestibulospinal reflex (VSR). Changes in Fos expression were also observed in the LRt and the PN. We suggest that sensory substitution, in which signals produced by a subject's own activity replace activity normally provided by macular stimulation, contributes to the recovery of microgravity-related postural and motor deficits.While no consistent increases in FRA expression occurred in vestibular IO regions 24h after launch, consistent increases in FRA expression occurred 24h after landing. We hypothesize that this asymmetrical pattern of gene expression resulted from (i). tonic microgravity experienced after launch counteracting the effects of increased phasic gravitational forces experienced during launch, and (ii). the tonic gravitational field experienced after landing potentiating the effects of increased phasic gravitational forces experienced during landing.The specificity of these results is demonstrated by an absence of direct gravity-related changes in Fos expression in other precerebellar structures such as the external cuneate nucleus, group X, and the dorsal column nuclei that transmit exteroceptive and proprioceptive signals to thalamic nuclei and somatosensory areas of the cerebral cortex. The gravity-related Fos and FRA expression changes in the IO and the LRt seen here are of interest in view of the important role their projections play in adaptive gain changes of the VOR and VSR during sustained visuo-vestibular and neck-vestibular stimulation.     

Fos and FRA protein expression in rat nucleus paragigantocellularis lateralis during different space flight conditions

The nucleus paragigantocellularis lateralis (LPGi) exerts a prominent excitatory influence over locus coeruleus (LC) neurons, which respond to gravity signals. We investigated whether adult albino rats exposed to different gravitational fields during the NASA Neurolab Mission (STS-90) showed changes in Fos and Fos-related antigen (FRA) protein expression in the LPGi and related cardiovascular, vasomotor, and respiratory areas. Fos and FRA proteins are induced rapidly by external stimuli and return to basal levels within hours (Fos) or days (FRA) after stimulation. Exposure to a light pulse (LP) 1 h prior to sacrifice led to increased Fos expression in subjects maintained for 2 weeks in constant gravity (either at approximately 0 or 1 G). Within 24 h of a gravitational change (launch or landing), the Fos response to LP was abolished. A significant Fos response was also induced by gravitational stimuli during landing, but not during launch. FRA responses to LP showed a mirror image pattern, with significant responses 24 h after launch and landing, but no responses after 2 weeks at approximately 0 or 1 G. There were no direct FRA responses to gravity changes. The juxtafacial and retrofacial parts of the LPGi, which integrate somatosensory/acoustic and autonomic signals, respectively, also showed gravity-related increases in LP-induced FRA expression 24 h after launch and landing. The neighboring nucleus ambiguus (Amb) showed completely different patterns of Fos and FRA expression, demonstrating the anatomical specificity of these results. Immediate early gene expression in the LPGi and related cardiovascular vasomotor and ventral respiratory areas may be directly regulated by excitatory afferents from vestibular gravity receptors. These structures could play an important role in shaping cardiovascular and respiratory function during adaptation to altered gravitational environments encountered during space flight and after return to earth.