Dataset Information

Impairment in extinction of contextual and cued fear following post-training whole-body irradiation.

ABSTRACT: Because of the use of radiation in cancer therapy, the risk of nuclear contamination from power plants, military conflicts, and terrorism, there is a compelling scientific and public health interest in the effects of environmental radiation exposure on brain function, in particular hippocampal function and learning and memory. Previous studies have emphasized changes in learning and memory following radiation exposure. These approaches have ignored the question of how radiation exposure might impact recently acquired memories, which might be acquired under traumatic circumstances (cancer treatment, nuclear disaster, etc.). To address the question of how radiation exposure might affect the processing and recall of recently acquired memories, we employed a fear conditioning paradigm wherein animals were trained, and subsequently irradiated (whole-body X-ray irradiation) 24?h later. Animals were given 2?weeks to recover, and were tested for retention and extinction of hippocampus-dependent contextual fear conditioning or hippocampus-independent cued fear conditioning. Exposure to irradiation following training was associated with reduced daily increases in body weights over the 22-days of the study and resulted in greater freezing levels and aberrant extinction 2?weeks later. This was also observed when the intensity of the training protocol was increased. Cued freezing levels and measures of anxiety 2?weeks after training were also higher in irradiated than sham-irradiated mice. In contrast to contextual freezing levels, cued freezing levels were even higher in irradiated mice receiving 5 shocks during training than sham-irradiated mice receiving 10 shocks during training. In addition, the effects of radiation on extinction of contextual fear were more profound than those on the extinction of cued fear. Thus, whole-body irradiation elevates contextual and cued fear memory recall.

SUBMITTER: Olsen RH

PROVIDER: S-EPMC4078460 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Impairment in extinction of contextual and cued fear following post-training whole-body irradiation.

Olsen Reid H J RH Marzulla Tessa T Raber Jacob J

Frontiers in behavioral neuroscience 20140702

Because of the use of radiation in cancer therapy, the risk of nuclear contamination from power plants, military conflicts, and terrorism, there is a compelling scientific and public health interest in the effects of environmental radiation exposure on brain function, in particular hippocampal function and learning and memory. Previous studies have emphasized changes in learning and memory following radiation exposure. These approaches have ignored the question of how radiation exposure might im ...[more]

PMID: 25071488

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Project description:Disproportionate, maladapted, and generalized fear are essential hallmarks of posttraumatic stress disorder (PTSD), which develops upon severe trauma in a subset of exposed individuals. Among the brain areas that are processing fear memories, the hippocampal formation exerts a central role linking emotional-affective with cognitive aspects. In the hippocampus, neuronal excitability is constrained by multiple GABAergic interneurons with highly specialized functions and an extensive repertoire of co-released neuromodulators. Neuropeptide Y (NPY) is one of these co-transmitters that significantly affects hippocampal signaling, with ample evidence supporting its fundamental role in emotional, cognitive, and metabolic circuitries. Here we investigated the role of NPY in relation to GABA, both released from the same interneurons of the dorsal dentate gyrus (DG), in different aspects of fear conditioning. We demonstrated that activation of dentate GABA neurons specifically during fear recall reduced cue-related as well as trace-related freezing behavior, whereas inhibition of the same neurons had no significant effects. Interestingly, concomitant overexpression of NPY in these neurons did not further modify fear recall, neither under baseline conditions nor upon chemogenetic stimulation. However, potentially increased co-release of NPY substantially reduced contextual fear, promoted extinction learning, and long-term suppression of fear in a foreground context-conditioning paradigm. Importantly, NPY in the dorsal DG was not only expressed in somatostatin neurons, but also in parvalbumin-positive basket cells and axoaxonic cells, indicating intense feedback and feedforward modulation of hippocampal signaling and precise curtailing of neuronal engrams. Thus, these findings suggest that co-release of NPY from specific interneuron populations of the dorsal DG modifies dedicated aspects of hippocampal processing by sharpening the activation of neural engrams and the consecutive fear response. Since inappropriate and generalized fear is the major impediment in the treatment of PTSD patients, the dentate NPY system may be a suitable access point to ameliorate PTSD symptoms and improve the inherent disease course.

Dataset Information

Impairment in extinction of contextual and cued fear following post-training whole-body irradiation.

Publications

Impairment in extinction of contextual and cued fear following post-training whole-body irradiation.

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