Abstract

The proposed deep space exploration to the moon and later to Mars will result in astronauts receiving significant chronic exposures to space radiation (SR). SR exposure results in multiple neurocognitive impairments. Recently, our cross-species (mouse/rat) studies reported impaired associative memory formation in both species following a chronic 6-month low dose exposure to a mixed field of neutrons (1 mGy/day for a total dose pf 18 cGy). In the present study, we report neutron exposure induced synaptic plasticity in the medial prefrontal cortex, accompanied by microglial activation and significant synaptic loss in the hippocampus. In a parallel study, neutron exposure was also found to alter fluorescence assisted single synaptosome LTP (FASS-LTP) in the hippocampus of rats, that may be related to a reduced ability to insert AMPAR into the post-synaptic membrane, which may arise from increased phosphorylation of the serine 845 residue of the GluA1 subunit. Thus, we demonstrate for the first time, that low dose chronic neutron irradiation impacts homeostatic synaptic plasticity in the hippocampal-cortical circuit in two rodent species, and that the ability to successfully encode associative recognition memory is a dynamic, multicircuit process, possibly involving compensatory changes in AMPAR density on the synaptic surface.

Highlights

  • We have previously shown that cognitive performance after space radiation (SR) exposure may arise due to compensatory changes in the composition of the HPC proteome, including differential expression of proteins involved in positive regulation of excitatory post-synaptic potential and protein localization to the synapse [26]

  • We extended the observations by studying the effects of such radiation exposures on long-term depression (LTD) at the synapse by stimulating at layer 2/3 and recording of layer 5 of the mPFC

  • We assessed whether low dose neutron exposure had an effect on CA1 pyramidal pyramidal neuronal dendritic dendritic length lengthand andbranching branchingcomplexity complexity(Figure

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Summary

Introduction

The second part of our study used fluorescence assisted single synaptosome LTP (FASS-LTP) analysis to perform a cross-species validation of HSP (i.e., LTP) changes in the HPC of rats that were concurrently exposed to chronic low dose and dose rate neutron irradiation [16] with the C57Bl/6 mice [4]. The FASS-LTP analysis of the hippocampi from rats identified a close to significant trend of reduced LTP after neutron exposure, but significant changes in the phosphorylation state of glutamate receptor subunits in rats that successfully encoded the SD associative recognition memory on the first attempt These data suggest that SR exposure impacts HSP in the hippocampal-cortical circuit, and that the ability to successfully encode associative recognition memory is a dynamic, multicircuit process, possibly involving compensatory changes in AMPA receptor (AMPAR) density on the synaptic surface

Results
PSD-95
Results in Dendritic
Chronic
Western Analyses of Radiation-Induced Changes in Synaptic Proteins
Fluorescence irradiated
Phosphorylation of serine at position of the
10. Paired
Animal Welfare
Rodent Subjects
Field Electrophysiological Recordings
Western Blot Analysis
Intracellular Dye Injections
Neuronal and Dendritic Reconstruction
Quantitative Analysis of Synapses and Myelin
4.10. Statistics
Full Text
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