Loss of promoter IV-driven BDNF expression impacts oscillatory activity during sleep, sensory information processing and fear regulation
| Autor: | Dennisse V. Jimenez, Keri Martinowich, Cameron Pollock, Robert J. Schloesser, Alisha Kardian, Julia L. Hill, Nicholas F. Hardy, Kristen R. Maynard |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Reflex Startle Sensory processing medicine.medical_treatment Hippocampus Prefrontal Cortex Sensory system Arousal Extinction Psychological Stress Disorders Post-Traumatic 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Neurotrophic factors medicine Animals Theta Rhythm Prefrontal cortex Promoter Regions Genetic Evoked Potentials Biological Psychiatry Prepulse inhibition Prepulse Inhibition Brain-Derived Neurotrophic Factor Electroencephalography Extinction (psychology) Fear Brain Waves Psychiatry and Mental health 030104 developmental biology nervous system Original Article Psychology Sleep Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | Posttraumatic stress disorder is characterized by hyperarousal, sensory processing impairments, sleep disturbances and altered fear regulation; phenotypes associated with changes in brain oscillatory activity. Molecules associated with activity-dependent plasticity, including brain-derived neurotrophic factor (BDNF), may regulate neural oscillations by controlling synaptic activity. BDNF synthesis includes production of multiple Bdnf transcripts, which contain distinct 5′ noncoding exons. We assessed arousal, sensory processing, fear regulation and sleep in animals where BDNF expression from activity-dependent promoter IV is disrupted (Bdnf-e4 mice). Bdnf-e4 mice display sensory hyper-reactivity and impaired electrophysiological correlates of sensory information processing as measured by event-related potentials (ERP). Utilizing electroencephalogram, we identified a decrease in slow-wave activity during non-rapid eye movement sleep, suggesting impaired sleep homeostasis. Fear extinction is controlled by hippocampal–prefrontal cortical BDNF signaling, and neurophysiological communication patterns between the hippocampus (HPC) and medial prefrontal cortex (mPFC) correlate with behavioral performance during extinction. Impaired fear extinction in Bdnf-e4 mice is accompanied by increased HPC activation and decreased HPC–mPFC theta phase synchrony during early extinction, as well as increased mPFC activation during extinction recall. These results suggest that activity-dependent BDNF signaling is critical for regulating oscillatory activity, which may contribute to altered behavior. |
| Databáze: | OpenAIRE |
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