The Neurolab Spacelab Mission: Neuroscience Research in Space, edited by Jay C. Buckey, Jr, MD; Jerry L. Homick, PhD. Houston, Tex: National Aeronautics and Space Administration, Lyndon B. Johnson Space Center. 333 pages. 2003.

On April 17, 1998, the Neurolab Spacelab mission lifted off from Kennedy Space Centre carrying 26 experiments dedicated to studying the effects of weightlessness on the brain and the nervous system. This book presents scientific reports for each major area of study on the 16-day flight. The categories include the balance system, sensory integration and navigation, nervous system development in weightlessness, blood pressure control, and circadian rhythms and sleep. Technical reports related to noteworthy procedures and necessary equipment as well as an overview of the mission are also included. Wonderful graphics and illustrations highlight the investigations' key findings. This review focuses on the research related to nervous system development in weightlessness and its implications for neonatal and fetal development. Approximately 60% of the muscular system works against gravity. Thus, the overriding question was-is gravity, or the loading that gravity brings, essential for normal development? Results of the 9 experiments when taken together suggest that there are critical periods when gravity is important for development. The answers pose implications for the future of our activities in long-term space exploration including colonization outside of Earth's gravity.

Motor System Development Depends on Experience: A Microgravity Study of Rats

Kalb R, Hillman D, Defelipe J, Garcia-Segura LM, Walton KD, and Llinas RR

The researchers asked the questions, "To what extent must animals learn to factor in the force of gravity when making neural calculations about movement? Are animals born knowing how to respond to gravity, or must the young nervous system learn to enter gravity into the equation?" In the presence of gravity, a 2-dimensional space is negotiated. However, in microgravity, a strategy must be developed in which to negotiate a 3-dimensional space. Three groups of rats were studied: flight, ground control, and basal control. The groups were further divided according to age; young rats were launched at day 8 and older rats were launched at day 14. Neurons from the cervical spinal cord, neocortex, and supraoptic nucleus of the hypothalamus were harvested on flight day 7 and 14, as well as a few hours after landing. After examining the evidence the researchers concluded that (1) many aspects of motor behavior are preprogrammed into an immature nervous system; (2) several motor behaviors are acquired as a function of the interaction of the developing organism and the rearing environment; and (3) widespread neuroanatomical differences between one-G- and microgravity-reared rats indicate that there is a structural basis for the adaptation to the rearing environment.

Neuromusclar Development Is Altered by Spaceflight

Riley DA, Wong-Riley MTT

A significant component of human neuromuscular development begins in utero and continues throughout the first year of life. Previous research has demonstrated that early removal of muscle loading markedly disrupts the neuromuscular development of weight-bearing muscles. It was hypothesized that raising young rats in microgravity to eliminate weight-bearing by the hindlimbs would compromise the nerve and muscle development of the soleus (weight-bearing leg muscle) and that the non-weight-bearing extensor digitorum longus leg muscle would not be affected. The spinal cords, soelus uscles, and extensor digitorum longus muscles were collected from 6 young rats on inflight day 15 and were compared with ground samples of age-matched controls. It was found that soleus development was the most disrupted as evidenced by decreased muscle fiber growth, increased sensitivity to muscle reloading injury, reduced growth of motor neuron terminals as well as a lowered ability of the nerves to use oxygen. Findings suggest that normal neuromuscular development depends upon loaded contractions during the formative period.

Gravity Plays an Important Role in Muscle Development and the Differentiation of Contractile Protein Phenotype

Adams GR, Haddad F, and Baldwin KM

Following birth, muscles are in an undifferentiated state with respect to their relative size, functional properties, and pattern of myosin heavy chain (MHC) gene expression, a family of proteins essential for muscle contraction. In infancy, various motor units express immature forms of MHC, designated as embryonic and neonatal isoforms, which are thought to be ineffective in opposing gravity and producing locomotion. It was hypothesized that weight-bearing activity is critical for inducing the normal expression of the slow MHC gene typical of adult antigravity muscles, and that thyroid hormone, rather than opposition to gravity, is necessary for expressing the adult type (IIb) essential for high-intensity muscle performance. The rats were randomly assigned to the following groups: (1) euthyroid-ground-control; (2) euthyroid-flight; (3) thyroid-deficient ground-control; and (4) thyroid-deficient flight. Data indicated that normal weight-bearing activity is essential for establishing body and muscle growth in neonatal animals and for expressing the motor gene necessary for supporting antigravity functions.

Early Development of Gravity Sensing Organs in Microgravity

Wiederhold ML, Gao W, Harrison JL, and Parker KA

Most animals sense gravity using dense stones called otoliths or statoliths that rest on the sensitive hairs of specialized gravity- and motion-sensing cells. The weight of the stones bends the hairs in the direction of the gravitational pull. The brain uses this information to determine position in the gravity field and the direction of movements. Data suggest that altered gravity does not affect the otoliths in adults; however, there may be profound effects in a developing organism. Pond snails and juvenile swordtail fish were studied after spaceflight. In the snails and later-stage larvae swordtail fish that developed in space, the total volume of the otoliths was 50% greater than in ground controls. Juvenile fish showed no significant difference in otolith size between flight- and ground-reared fish. The fish data indicate there is a critical period relatively early in development in which the regulatory mechanism, which optimizes otolith weight, can act. If humans were to be conceived and reared in microgravity, it is unknown whether their otoliths would be abnormally large while in space, or whether they would revert to normal size some time after introduction to one-G. The researchers also question whether human otolith-related reflexes developed in microgravity would function normally in one-G.

The Development of an Insect Gravity Sensory System in Space (Crickets in Space)

Horn ER, Kamper G, and Neubert J

The overall aim of the study was to reveal how the development of a gravity sense organ, a behavior related to gravity, and a nerve system sensitive to gravity would be affected by gravity deprivation. Crickets were the model because they possess an external gravity sense organ that induces a compensatory head response, and can regenerate after damage. Eggs and first-, fourth-, and sixth-stage larvae were sent into space to explore the possibility of an age-related sensitivity to microgravity. Another group was exposed to three-G for the same amount of time. It was concluded that gravity is necessary for normal development and that deprivation causes disturbances in neuronal activity or behavior (both microgravity and hypergravity activate adaptive mechanisms). Readaptation to normal one-G conditions after termination of micro- or hypergravity is faster when more parallel channels exist that can control and affect the specific behavioral response. A high susceptibility exists before and during the period of cell proliferation in the neuronal network underlying behavior.

Development of the Vestibular System in Microgravity

Raymond J, Dememes D, Blanc E, and Dechesne CJ

In the visual and auditory systems, seeing and hearing experiences profoundly affect the developing central nervous system and control its final organization. It is known that there are critical periods of development when sensory experience is necessary for normal maturation. It is not known whether gravity is essential in normal development of the vestibular (balance) system and the connections it makes. The aim was to investigate the effect of weightlessness on both the development of a gravity sensor (the utricle in the inner ear) and on the relay of information from this sensor to the brain. Tissues were collected from ground control and flight rats on flight day 8, flight day 15, and 8 hours after landing. No effect of microgravity on sensory cells and neuron connections was found. However, the flight rats demonstrated a lack of connections into the vestibular nuclei from the cerebellum (concerned with balance and coordination). This suggests that lack of gravity did have an effect on the development of nerve connections in the brain, but not in the gravity sensor itself. Therefore, gravity may be important in the normal development of the balance system.

Development of the Aortic Baroreflex in Microgravity

Shimizu T, Yamasaki M, Waki H, Katsuda S, Oishi H, Katahira K, Nagayama T, Miyake M, and Miyamoto Y

The primary baroreceptors located in the aorta and carotid arteries send messages to the brain to raise or lower blood pressure. In contrast to a gravity field where moving from a lying to sitting or standing position powerfully stimulates these baroreflexes, the stimuli in microgravity are markedly reduced. If the reduction occurs when the pathways that control the baroreflexes are being developed, it is possible that either the structure or the function of the baroreceptors may be permanently changed. The young rats (inflight for 16 days) were studied on the landing day and at 30 days after landing once they had readapted to Earth's gravity. It was found that compared to controls, the flight rats had fewer unmyelinated nerve fibers in their aortic nerves, lower baroreflex sensitivity, significantly lower contraction ability and wall tension of the aorta, and a reduced number of smooth muscle cells in the aorta. At 30 days, the sensitivity of the baroreflex showed no difference between the flight rats and the control groups, although the unmyelinated fibers of the aortic nerve remained reduced in the flight rats. Thus, spaceflight does affect development of the aortic baroreflex; however, the function of the blood pressure control system can readapt to Earth's gravity if the rats return before maturation. There is the possibility that structural differences in the afferent pathway (aortic nerve) may remain permanently.

Neural Development Under Conditions of Spaceflight

Temple MD, Denslow MJ, Kosik KS, and Steward O

An important aspect of brain function (hippocampus and related structures) is the ability to form memories of the environment, called "cognitive maps." Animals who experience complex environments during early development have higher brain weight, increased cortical thickness, and increases in the number of synapses on cortical neurons, all of which indicate that experience affects the development of neural circuitry. Normal development requires the experience to occur within a certain window of time during maturation. It is unknown whether the absence of gravitational cues would affect the normal development of the spatial cognitive navigation system. Litters of rats aged postnatal day 8 or 14 underwent spaceflight for 16 days. Upon return to Earth, they were tested for their ability to remember spatial information and navigate using a variety of tests. Electrophysiological analysis of hippocampal function and histological analyses of flight hippocampus were also performed. The researchers concluded that development in an environment lacking gravity does not produce any permanent change in an animal's ability to use spatial information and form memories. There were no detectable differences in hippocampal anatomy, biochemistry, or synaptic plasticity. Results indicate that systems critical for spatial cognitive function can readily readapt to a gravitational field even when very early development is spent in a gravity-free environment.

The book is a fascinating read of the Neurolab mission as part of the Spacelab series. It is a map of where science has been, a summary of what was learned, and a guide for research in the future.

The Effect of Weightlessness on the Developing Nervous System

Nowakowski RS and Hayes NL

To study the effects of loss of gravity on cell proliferation and migration within the neocortex, developing brains of prenatal mice were labeled during spaceflight using two markers of DNA synthesis (tritiated thymidine and bromodeoxyuridine). The brains were preserved in fixative and returened to Earth for postflight analysis. It was determined that there were significant differences in the development of the brain in fetal mice in space versus those maintained at the Kennedy Space Center under identical conditions. Work continues to determine precisely how brain development is modified in a weightless environment.

M. Terese Verklan, PhD, CCNS, RNC

Associate Professor, University of Texas Health Science Center at Houston