Skilled movement and posture deficits in rat string-pulling behavior following low dose space radiation (²⁸Si) exposure

Abstract

Deep space flight missions beyond the Van Allen belt have the potential to expose astronauts to space radiation which may damage the central nervous system and impair function. The proposed mission to Mars will be the longest mission-to-date and identifying mission critical tasks that are sensitive to space radiation is important for developing and evaluating the efficacy of counter measures. Fine motor control has been assessed in humans, rats, and many other species using string-pulling behavior. For example, focal cortical damage has been previously shown to disrupt the topographic (i.e., path circuity) and kinematic (i.e., moment-to-moment speed) organization of rat string-pulling behavior count to compromise task accuracy. In the current study, rats were exposed to a ground-based model of simulated space radiation (5 cGy ²⁸Silicon), and string-pulling behavior was used to assess fine motor control. Irradiated rats initially took longer to pull an unweighted string into a cage, exhibited impaired accuracy in grasping the string, and displayed postural deficits. Once rats were switched to a weighted string, some deficits lessened but postural instability remained. These results demonstrate that a single exposure to a low dose of space radiation disrupts skilled hand movements and posture, suggestive of neural impairment. This work establishes a foundation for future studies to investigate the neural structures and circuits involved in fine motor control and to examine the effectiveness of counter measures to attenuate the effects of space radiation on fine motor control.

Introduction

Deep space flight missions will expose astronauts to galactic cosmic radiation (GCR). Current estimates suggest that astronauts will be exposed to ∼13 cGy of GCR during each year of a mission to Mars [1], the majority of which will be incurred while in transit. The structure of the spacecraft will offer a degree of shielding to the astronauts, reducing the dose and altering the GCR ion spectrum from that seen in free space. The “Local-Field” spectrum (the radiation spectrum that the internal organs of astronauts will receive within the spacecraft) predicts that the majority of the physical and dose-equivalent space radiation (SR) dose will arise from Z < 15 particles [2].

The impact that SR exposure may have on many aspects of astronaut health has been increasingly investigated. Ground-based rodent studies have shown that SR exposure induces significant changes in many aspects of neurotransmission within the hippocampus [[3], [4], [5], [6], [7], [8], [9]] and other parts of the brain [[10], [11], [12], [13]]. There is increasing evidence that SR exposure impairs performance in several cognitive tasks, including those requiring cognitive flexibility [[10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]]. Marked inter-individual differences exist in cognitive flexibility performance of the irradiated subjects, with some rats having performance metrics comparable to shams, while others completely fail to reach criterion in cognitive tasks [[10], [11], [12],14,16,21]. Our previous studies indicate that ∼33 % of irradiated rats exhibit cognitive performance metrics that fall below the 5th percentile of the performance metrics of the sham cohorts [15,16,20]. Additional and/or latent performance decrements may be present that are not apparent in the irradiated rodents with apparently normal cognitive performance. We have recently shown that rats exposed to 5 cGy 600 MeV/n ²⁸Si had no detectable constrained cognitive flexibility (ATSET task) performance issues but exhibited significant impairments in unconstrained cognitive flexibility tasks [11]. Moreover, there are latent ATSET deficits in rats exposed to Si [22] or neutrons [15] that had apparently perfect ATSET performance under normal rested conditions, which become manifested after mild sleep fragmentation. While there are some individuals that exhibit widespread performance decrements, in general, there does not appear to be a consistent performance impairment in tasks regulated by different brain regions, or that investigate different cognitive domains [10,11,15]. Thus, risk estimates based upon the impact of SR on a single process are likely to severely underestimate the negative impact of SR on astronaut performance.

Astronauts not only have to be cognitively proficient, but they also must be able to physically conduct tasks on the mission During parabolic flight, astronauts that had been on prior space missions exhibited decreased knot tying ability in a surgical task [23]. The combined effects of space flight stressors, including GCR and microgravity, may act synergistically to influence the central nervous system (CNS) and impair function. However, it is not yet known whether GCR exclusively influences skilled motor control. Ground-based rodent studies have demonstrated that SR exposure results in gross motor deficits [[24], [25], [26], [27]]. However, the impact that SR exposure has on fine motor control which supports many daily activities, such as tool and mission control manipulation, has not been established yet. Given the high level of coordination between multiple processes and brain regions, and the reported issues in neurotransmission and inter-connectivity between brain regions after SR exposure [13], it is conceivable that fine motor skills may be more sensitive to SR exposure than gross motor functions.

The present study examined the performance of rat string-pulling behavior in which animal’s balance on their hindlimbs while making hand-over-hand movements to retrieve a food reward attached to the end of the string. Not only does the task involve skilled hand use for performance, but the motor behavior both rats and humans elicit on the task is similar [[28], [29], [30]]. Efficient task performance is dependent upon motor cortex (M1) control, as lesions of this cortical area impair the topographic and kinematic organization of rat string-pulling behavior and compromise task accuracy [31]. Accordingly, the damage produced by SR ions may also impair the structures or systems involved in string-pulling behavior. Therefore, the current study evaluated the effects of a low dose exposure to 5 cGy of 600 MeV/n ²⁸Si ions on the organization of string-pulling behavior in rats.