1National Aeronautics and Space Administration, Ames Research Center, Moffett Field, California 94035; 2Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri 63110; 3Department of Physiology, University of Tsukuba, Tsukuba 305-8575; 4Toyohashi University of Technology, Toyohashi 441-8580, Japan; 5Department of Otolaryngology/Head-Neck Surgery, Oregon Health Sciences University, Portland, Oregon 97201; and 6Department of Biological Sciences, Florida Institute of Technology, Melbourne, Florida 32901
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ABSTRACT |
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Boyle, Richard, Allen F. Mensinger, Kaoru Yoshida, Shiro Usui, Anthony Intravaia, Timothy Tricas, and Stephen M. Highstein. Neural Readaptation to Earth's Gravity Following Return From Space. J. Neurophysiol. 86: 2118-2122, 2001. The consequence of exposure to microgravity on the otolith organs was studied by recording the responses of vestibular nerve afferents supplying the utricular otolith organ to inertial accelerations in four toadfish, Opsanus tau, sequentially for 5 days following two National Aeronautics and Space Administration shuttle orbital flights. Within the first day postflight, the magnitude of response to an applied translation was on average three times greater than for controls. The reduced gravitational acceleration in orbit apparently resulted in an upregulation of the sensitivity of utricular afferents. By 30 h postflight, responses were statistically similar to control. The time course of return to normal afferent sensitivity parallels the reported decrease in vestibular disorientation in astronauts following return from space.
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INTRODUCTION |
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It is of fundamental importance
that organisms remain orientated within their terrestrial environment.
Vertebrates possess a gravitoinertial sensing system, the utricular and
saccular otolith organs that sense the sum of inertial and
gravitoinertial forces due to head translation and head tilt relative
to gravitational vertical and transform the vector sum of the imposing
accelerations into a neural code. Since inertial and gravitational
accelerations are indistinguishable (Einstein's equivalency principle)
(Einstein 1945), both forces act equally on the otolith
maculae. This code is combined with angular acceleration signals
obtained from the semicircular canals and with information derived from
other sensory modalities to compute a central representation of the
body in space called the gravitoinertial vector. Thus the CNS resolves the ambiguity of gravity and self-motion and thereby maintains balance
and equilibrium under varying conditions.
Exposure to microgravity imposes an extreme condition to which the
traveler must adapt. Many, if not most, human travelers experience some
disorientation during the first few days in microgravity called space
adaptation syndrome akin to terrestrial motion sickness (Reason
and Brandt 1975). From the earliest manned missions, it was
evident that adjustments to the microgravity environment in-flight and
on return to Earth's 1 g occur (Black et al.
1999
; Reschke et al. 1994
). These adaptation
mechanisms are conjectural and range from neural to structural changes
or both. We studied the neural readaptation to Earth's 1 g
using electrophysiological techniques to measure the response
characteristics of utricular nerve afferents in fish on return from an
exposure to microgravity.
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METHODS |
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Six oyster toadfish, Opsanus tau, weighing 150-700
g, were individually housed in seawater tanks aboard two NASA shuttles. Fish were returned to the laboratory where all experiments were performed within ~10 h of the shuttle landing. Surgical procedures are similar to Boyle and Highstein (1990) and were
performed in accordance with the American Physiological Society Animal
Care Guidelines and approved by the Institutional Animal Care and Use Committee. Fish were anesthetized with MS222 (Sigma) and
secured in a Plexiglas tank placed atop an experimental table. A
craniotomy exposed the utricle and its afferent nerve. Intra- and
extracellular potentials were recorded from individual afferents using
glass microelectrodes (2 M LiCl2). Potentials
were conventionally amplified filtered, displayed, and converted to
standard pulses. The experimental apparatus allowed manual yaw rotation
about Earth vertical and repositioning of animal for translational
acceleration parallel to Earth horizon and/or static tilt with respect
to gravity. Fish could be repositioned in a 360° circle such that the
translational acceleration was delivered along any direction in the
horizontal head plane and the acceleration was specifically directed,
e.g., nose-down (pitch) or side-down (roll). Static sensitivity of
otolith afferents to gravity was observed both in control and
postflight fish. Afferent recordings were typically compromised by the
manual repositioning of the table, and thus no reliable values of
magnitude and change of magnitude of static sensitivity were possible.
Position and motion of the fish were sensed by linear and rotary
potentiometers and led, along with the afferent nerve pulses, to a
computer interface (CED 1401Plus) connected to a Macintosh computer.
Spike2 acquisition software, and Igor (WaveMetrics) analysis package
were used. Statistical comparisons used the nonparametric unpaired
Mann-Whitney or paired Spearman rank correlation tests, and indicated
levels of statistical probability are two-tailed values (Instat
software package).
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RESULTS |
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Four toadfish were flown on the STS-90 "Neurolab" mission (17 days) and two aboard the STS-95 mission (9 days); two fish survived Neurolab and both survived STS-95. Responses of utricular afferents to gravitational (tilt) and inertial (translation) accelerations were recorded from four flight fish.
Control responses were obtained from 32 utricular afferents in three
fish. Figure 1 shows the firing rate
response (top, in imp/s) to a sinusoidal change in linear
position (LP, bottom). In Fig. 1A, the fish was
first rotated about the vertical axis in a counter-clockwise step to a
90° head (and body) angle. The resulting translational acceleration
(LA, Fig. 1B) was directed to the right, and ipsilateral to
the recorded afferent, along the inter-labyrinth axis, and maximally
excited the afferent. The averaged response to five stimulus cycles had
a maximal sensitivity of 2,230 imp · s1 · g
1 (Fig. 1B; see Table
1).
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Hair cell bundles are morphologically polarized (Wersäll
1956); and hair cell's receptor potentials are directionally
sensitive to bundle displacement (Hudspeth and Corey
1977
; Shotwell et al. 1981
). Directional
selectivity of utricular afferents are distributed in a fanlike shape
(Fernández and Goldberg 1976b
) as expected from
hair cell orientations in the utricular macula (Spoendlin 1966
). Figure 2 shows the test
used to determine the directional selectivity of individual afferents
in control (A) and postflight (B) fish. A
sinusoidal translational acceleration along an Earth-parallel plane was
delivered at successive 15° positions after the animal was stepped
around a 360° circle. Head angle (°) was defined using a right-hand
rule relative to the laboratory: a positive acceleration at 0°
represents a forward movement directed out the animal's snout and one
at 90° a movement directed out the animal's right ear. Directional
selectivity was determined by plotting the response sensitivity and
phase relative to head angle. The data were fit by a rectified, cosine
function (dashed lines in Fig. 2, A and B), and
correspondence between the tested and predicted responses reflects the
sharpness of directional tuning. Control afferent in Fig. 2A
was sharply tuned and directionally selective to acceleration directed
along the inter-labyrinth axis. All control afferents were
directionally selective, and the maximal response vectors spanned
360° of head angle.
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In early postflight fish utricular afferents were hypersensitive to
translational acceleration (Figs. 1-3)
and directionally selective (Fig. 2B). One the first
afferents recorded at 10.5 h postflight illustrates the striking
increase in response sensitivity when stimulated at ±0.0026
g acceleration or ±0.025 cm displacement (Fig. 1,
C and D). The discharge modulation was about ±30
imp/s, yielding an afferent maximal sensitivity was 11,412 imp · s1g
1, nearly
sevenfold greater than the control mean and about threefold greater
than the maximum response obtained in any individual control afferent
(4,136 imp · s
1g
1; Table
1).
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Data for both STS-90 and STS-95 shuttle missions are presented in the form of a probability plot (Fig. 3) to show the initial increase and recovery of response sensitivity. The data in this figure and in Table 1 are divided into groups based on time postflight. Maximum sensitivity of each afferent is plotted as a percentage of population sensitivity whose value is less than the individual sensitivity. For ~60% of the afferents (14/24) in both fish on STS-95 (filled circles), labeled STS-95: 1 + 2, the sensitivity recorded 10-16 h postflight was dramatically enhanced relative to control (crosses). Within this time group, the afferent sensitivity of the entire sample (n = 24) was roughly triple that in control (P < 0.01). The afferent sensitivity returns to near normal at the recorded time of 29.5-32 h postflight and remains within normal range after 5 days postflight.
To examine for possible recording bias, all measured parameters were compared between control and postflight afferents. No statistical difference was found in the range and mean of afferent discharge rate (imp/s) and regularity of discharge (standard deviation of the interval divided by the mean interspike interval) between postflight and control fish. An equal distribution of head angles evoking maximum and minimum response modulations of utricular afferents in postflight, similar to that observed in control fish, and response phase (°) were also found.
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DISCUSSION |
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The increase in sensitivity of certain otolith afferents following
space travel is most likely due to exposure of the animal to
microgravity. The results, however, should be regarded as preliminary as single afferents were not studied sequentially. The following are
speculations concerning potential mechanisms: an increase in transducer
sensitivity, a temporary structural alteration affecting the
mechanoreception of the otolith, otolith-stereociliary coupling causing
enhanced bundle deflection for a given movement, or a pre- or
postsynaptic alteration in the strength of synaptic transmission. The
number of synaptic ribbons in certain type II hair cells in rodent is
labile, increasing following exposure to microgravity (Ross
1993, 1994
, 2000
). Toadfish possess only type II hair cells and
the afferent number of synaptic boutons and its response sensitivity to
vestibular stimulation are correlated (Boyle et al.
1991
). Thus an increase in number of synaptic ribbons in
toadfish otolith hair cells following exposure to microgravity could
potentially explain the present results.
If the otolith structure is arranged for optimal responses in 1 g, mechanical alterations may also occur in microgravity. For example, loss of gravitational force might displace the otolith relative to the macula, thus affecting neural responses. Altered gravity conditions might also trigger an adaptive response of the
weight-lending structures (Wiederhold et al. 1997,
2000
). Other reports suggest qualitative changes in otolith
structure following space flight (Lychakov 1991
;
Susuki et al. 1993
). However, Lim et al.
(1974)
and Sondag et al. (1995)
could not
demonstrate any change at the otoconial level after prolonged
hypergravity by centrifugation. It is clear that more experiments under
controlled states of altered gravity are required to determine the
structural and developmental response of the otolith and the
consequence of space flight on otolith function.
Adaptation of otolith hair cell receptor potentials occurs to prolonged
deviation of their sensory hair bundle (Eatock et al.
1987; Fernández and Goldberg 1976a
;
Goldberg et al. 1990
). Unweighting of the otolith mass
in microgravity might potentially cause an adaptation of receptor
potentials. That enhanced sensitivity remained for
24 h in toadfish
afferents, substantially longer than the suggested time course of
adaptation, is inconsistent with this view. Pioneering efforts at
recording from otolith afferents in microgravity were performed by
Bracchi et al. (1975)
and Gualtierotti (1977)
; however, the results are difficult to interpret.
Otolith sensors provide a major input to the internal representation of
the gravitoinertial vector. Thus an abnormal otolith component should
have profound effects on the orientation of the organism and has been
hypothesized to be causal in vestibular disorientation or space
adaptation syndrome. The demonstrated time course in the altered
otolith responses parallels the time course of disorientation
experienced by space travelers and gives support to this hypothesis. In
a complimentary study in another species of fish, the gain of an
otolith-related vestiobuloocular reflex was significantly increased
within the first postflight week, and returned to control levels in the
second postflight week, of space missions (Sebastian et al.
2001).
The earliest recordings began 10 h after STS-95 landing, and to
what extent this delay affects the interpretation of the data is
indeterminate. Because of enhanced afferent sensitivity, the initial
postflight results were limited to fewer stimulus frequencies (1-2 Hz)
and lower amplitudes than delivered in control tests. These
restrictions in stimulus parameters were required to minimize discharge
nonlinearity (Boyle and Highstein 1990). Sensitivity on
average declined from day 2 to 4, and larger stimulus
amplitudes could be progressively applied. The first single-unit
recordings after the STS-90 flight began 53 h after landing, well
after the postflight recovery time observed in the STS-95 fish.
Significantly the directional tuning of afferents remained unchanged
after exposure to microgravity. Therefore we would not expect
significant remodeling of the spatial extent of dendritic arbors of
afferents within the sensory epithelium to have occurred.
To date the toadfish utricular nerve has only been crudely evaluated at one frequency with a hand-powered linear sled. If the fish utricle bears any resemblance to similar epithelia studied in other species, more complete functional evaluations of afferents will no doubt demonstrate considerable diversity. It therefore remains to be tested whether a specific population of afferents demonstrated increased sensitivity or whether this finding is a general feature of all cells.
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ACKNOWLEDGMENTS |
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This work was supported by grants from National Aeronautics and Space Administration Ames (2-945), the National Institute on Deafness and Other Communication Disorders (PO-1 DC-01837), and the National Space Development Agency of Japan.
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FOOTNOTES |
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Address for reprint requests: R. Boyle, Ames Research Center, M/S 239-11, NASA, Moffett Field, CA 94035-1000 (E-mail: rboyle{at}mail.arc.nasa.gov).
Received 4 December 2000; accepted in final form 27 April 2001.
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REFERENCES |
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