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Effects of microgravity on vestibular development and function in rats: genetics and environment

Our anatomical and behavioral studies of embryonic rats that developed in microgravity suggest that the vestibular sensory system, like the visual system, has genetically mediated processes of development that establish crude connections between the periphery and the brain. Environmental stimuli also regulate connection formation including terminal branch formation and fine-tuning of synaptic contacts. Axons of vestibular sensory neurons from gravistatic as well as linear acceleration receptors reach their targets in both microgravity and normal gravity, suggesting that this is a genetically regulated component of development. However, microgravity exposure delays the development of terminal branches and synapses in gravistatic but not linear acceleration-sensitive neurons and also produces behavioral changes. These latter changes reflect environmentally controlled processes of development.

manned

Effects of heat stress on baroreflex function in humans

INTRODUCTION: Heat stress significantly reduces orthostatic tolerance in humans. The mechanism(s) causing this response remain unknown. The purpose of this review article is to present data pertaining to the hypothesis that reduced orthostatic tolerance in heat stressed individuals is a result of heat stress induced alterations in baroflex function. METHODS: In both normothermic and heat stressed conditions baroreflex responsiveness was assessed via pharmacological and non-pharmacological methods. In addition, the effects of heat stress on post-synaptic vasoconstrictor responsiveness were assessed. RESULTS: Generally, whole body heating did not alter baroreflex sensitivity defined as the gain of the linear portion of the baroreflex curve around the operating point. However, whole body heating shifted the baroreflex curve to the prevailing (i.e. elevated) heart rate and muscle sympathetic nerve activity. Finally, the heat stress impaired vasoconstrictor responses to exogenous administration of adrenergic agonists. CONCLUSION: Current data do not support the hypothesis that reduced orthostatic tolerance associated with heat stress in humans is due to impaired baroreflex responsiveness. This phenomenon may be partially due to the effects of heat stress on reducing vasoconstrictor responsiveness.

Review, Tutorial

Spaceflight induces changes in the synaptic circuitry of the postnatal developing neocortex

The establishment of the adult pattern of neocortical circuitry depends on various intrinsic and extrinsic factors, whose modification during development can lead to alterations in cortical organization and function. We report the effect of 16 days of spaceflight [Neurolab mission; from postnatal day 14 (P14) to P30] on the neocortical representation of the hindlimb synaptic circuitry in rats. As a result, we show, for the first time, that development in microgravity leads to changes in the number and morphology of cortical synapses in a laminar-specific manner. In the layers II/III and Va, the synaptic cross-sectional lengths were significantly larger in flight animals than in ground control animals. Flight animals also showed significantly lower synaptic densities in layers II/III, IV and Va. The greatest difference was found in layer II/III, where there was a difference of 344 million synapses per mm(3) (15.6% decrease). Furthermore, after a 4 month period of re-adaptation to terrestrial gravity, some changes disappeared (i.e. the alterations were transient), while conversely, some new differences also appeared. For example, significant differences in synaptic density in layers II/III and Va after re-adaptation were no longer observed, whereas in layer IV the density of synapses increased notably in flight animals (a difference of 185 million synapses per mm(3) or 13.4%). In addition, all the changes observed only affected asymmetrical synapses, which are known to be excitatory. These results indicates that terrestrial gravity is a necessary environmental parameter for normal cortical synaptogenesis. These findings are fundamental in planning future long-term spaceflights.

Non-NASA Center

Simulation studies of vestibular macular afferent-discharge patterns using a new, quasi-3-D finite volume method

A quasi-three-dimensional finite-volume numerical simulator was developed to study passive voltage spread in vestibular macular afferents. The method, borrowed from computational fluid dynamics, discretizes events transpiring in small volumes over time. The afferent simulated had three calyces with processes. The number of processes and synapses, and direction and timing of synapse activation, were varied. Simultaneous synapse activation resulted in shortest latency, while directional activation (proximal to distal and distal to proximal) yielded most regular discharges. Color-coded visualizations showed that the simulator discretized events and demonstrated that discharge produced a distal spread of voltage from the spike initiator into the ending. The simulations indicate that directional input, morphology, and timing of synapse activation can affect discharge properties, as must also distal spread of voltage from the spike initiator. The finite volume method has generality and can be applied to more complex neurons to explore discrete synaptic effects in four dimensions.

NASA Center ARC

Time-dependent influence of sensorimotor set on automatic responses in perturbed stance

These experiments tested the hypothesis that the ability to change sensorimotor set quickly for automatic responses depends on the time interval between successive surface perturbations. Sensorimotor set refers to the influence of prior experience or context on the state of the sensorimotor system. Sensorimotor set for postural responses was influenced by first giving subjects a block of identical backward translations of the support surface, causing forward sway and automatic gastrocnemius responses. The ability to change set quickly was inferred by measuring the suppression of the stretched antagonist gastrocnemius responses to toes-up rotations causing backward sway, following the translations. Responses were examined under short (10-14 s) and long (19-24 s) inter-trial intervals in young healthy subjects. The results showed that subjects in the long-interval group changed set immediately by suppressing gastrocnemius to 51% of translation responses within the first rotation and continued to suppress them over succeeding rotations. In contrast, subjects in the short-interval group did not change set immediately, but required two or more rotations to suppress gastrocnemius responses. By the last rotation, the short-interval group suppressed gastrocnemius responses to 33%, similar to the long-interval group of 29%. Associated surface plantarflexor torque resulting from these responses showed similar results. When rotation and translation perturbations alternated, however, the short-interval group was not able to suppress gastrocnemius responses to rotations as much as the long-interval group, although they did suppress more than in the first rotation trial after a series of translations. Set for automatic responses appears to linger, from one trial to the next. Specifically, sensorimotor set is more difficult to change when surface perturbations are given in close succession, making it appear as if set has become progressively stronger. A strong set does not mean that responses become larger over consecutive trials. Rather, it is inferred by the extent of difficulty in changing a response when it is appropriate to do so. These results suggest that the ability to change sensorimotor set quickly is sensitive to whether the change is required after a long or a short series of a prior different response, which in turn depends on the time interval between successive trials. Different rate of gastrocnemius suppression to toes-up rotation of the support surface have been reported in previous studies. This may be partially explained by different inter-trial time intervals demonstrated in this study.

NASA Discipline Neuroscience

Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

NASA Discipline Neuroscience

Evidence of a sensory processing unit in the mammalian macula

We cut serial sections through the medial part of the rat vestibular macula for transmission electron microscopic (TEM) examination, computer-assisted 3-D reconstruction, and compartmental modeling. The ultrastructural research showed that many primary vestibular neurons have an unmyelinated segment, often branched, that extends between the heminode (putative site of the spike initiation zone) and the expanded terminal(s) (calyx, calyces). These segments, termed the neuron branches, and the calyces frequently have spine-like processes of various dimensions with bouton endings that morphologically are afferent, efferent, or reciprocal to other macular neural elements. The major questions posed by this study were whether small details of morphology, such as the size and location of neuronal processes or synapses, could influence the output of a vestibular afferent, and whether a knowledge of morphological details could guide the selection of values for simulation parameters. The conclusions from our simulations are (1) values of 5.0 k omega cm2 for membrane resistivity and 1.0 nS for synaptic conductance yield simulations that best match published physiological results; (2) process morphology has little effect on orthodromic spread of depolarization from the head (bouton) to the spike initiation zone (SIZ); (3) process morphology has no effect on antidromic spread of depolarization to the process head; (4) synapses do not sum linearly; (5) synapses are electrically close to the SIZ; and (6) all whole-cell simulations should be run with an active SIZ.

NASA Center ARC

Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog

The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated frog labyrinth were varied in order to assess their role in influencing and mediating synaptic transmission at the hair cell-afferent fiber synapse. Experiments employed intracellular recordings of synaptic activity from VIIIth nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory postsynaptic potentials were detected and parameters quantified by computer algorithms. Particular attention was focused on cationic effects upon excitatory postsynaptic potential frequency of occurrence and excitatory postsynaptic potential amplitude, in order to discriminate between pre- and postsynaptic actions. Because the small size of afferents preclude long term stable recordings, alterations in cationic concentrations were applied transiently and their peak effects on synaptic activity were assessed. Increases in extracellular K+ concentration of a few millimolar produced a large increase in the frequency of occurrence of excitatory postsynaptic potentials with little change in amplitude, indicating that release of transmitter from the hair cell is tightly coupled to its membrane potential. Increasing extracellular Na+ concentration resulted in an increase in excitatory postsynaptic potential amplitude with no significant change in excitatory postsynaptic potential frequency of occurrence, suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions. Decreases in extracellular Ca2+ concentration had little effect upon excitatory postsynaptic potential frequency, but increased excitatory postsynaptic potential frequency and amplitude. These findings suggest that at higher concentrations Ca2+ act presynaptically to prevent transmitter release and postsynaptically to prevent Na+ influx during the generation of the excitatory postsynaptic potential. The influences of these ions on synaptic activity at this synapse are remarkably similar to those reported at the vertebrate neuromuscular junction. The major differences between these two synapses are the neurotransmitters and the higher resting release rate and higher sensitivity of release to increased K+ concentrations of the hair cells over that of motor nerve terminals. These differences reflect the functional roles of the two synapses: the motor nerve terminal response in an all-or-nothing signal consequent from action potential invasion, while the hair cell releases transmitter in a graded fashion, proportionate to the extent of stereocilial deflection. Despite these differences between the two junctions, the similar actions of these elemental cations upon synaptic function at each implies that these ions may participate similarly in the operations of other synapses, independent of the neurotransmitter type.(ABSTRACT TRUNCATED AT 400 WORDS).

NASA Discipline Neuroscience