Abstract
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.
Highlights
Investigating electrophysiological changes in neural and oscillatory activity in behaving animals allows researchers to study circuit dysfunction in disease models
Using a combination of behavior testing and in vivo electrophysiology, we demonstrate a number of phenotypes relevant to PTSD including sensory hyper-reactivity and impaired neural correlates of sensory information processing as measured studies, the mice were recorded for 48 h in a homecage environment with only the final 24 h included in the final analysis
Following sound 1 (S1), we found significantly decreased event-related spectral perturbation (ERSP) and intertrial phase coherence (ITC) beta frequency response in Bdnf-e4 mice compared with WT (Figures 1h and k)
Summary
Investigating electrophysiological changes in neural and oscillatory activity in behaving animals allows researchers to study circuit dysfunction in disease models. Plasticity molecules contribute to coordination and timing synchronized oscillatory activity by influencing synaptic strength and balancing synaptic inhibition versus excitation.[8,9] disruptions in expression of brainderived neurotrophic factor (BDNF), which has a key role in regulating synaptic plasticity in the brain, may influence oscillatory activity. A link between BDNF signaling, regulation of oscillatory activity and behavioral performance has not been thoroughly established
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
