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REM sleep is important for the processing of emotional memories, including fear memories. Rhythmic interactions, especially in the theta band, between the medial prefrontal cortex (mPFC) and limbic structures are thought to play an important role, but the ways in which memory processing occurs at a mechanistic and circuits level are largely unknown. To investigate how rhythmic interactions lead to fear extinction during REM sleep, we used a biophysically based model that included the infralimbic cortex (IL), a part of the mPFC with a critical role in suppressing fear memories. Theta frequency (4–12 Hz) inputs to a given cell assembly in IL, representing an emotional memory, resulted in the strengthening of connections from the IL to the amygdala and the weakening of connections from the amygdala to the IL, resulting in the suppression of the activity of fear expression cells for the associated memory. Lower frequency (4 Hz) theta inputs effected these changes over a wider range of input strengths. In contrast, inputs at other frequencies were ineffective at causing these synaptic changes and did not suppress fear memories. Under post-traumatic stress disorder (PTSD) REM sleep conditions, rhythmic activity dissipated, and 4 Hz theta inputs to IL were ineffective, but higher-frequency (10 Hz) theta inputs to IL induced changes similar to those seen with 4 Hz inputs under normal REM sleep conditions, resulting in the suppression of fear expression cells. These results suggest why PTSD patients may repeatedly experience the same emotionally charged dreams and suggest potential neuromodulatory therapies for the amelioration of PTSD symptoms. SIGNIFICANCE STATEMENT Rhythmic interactions in the theta band between the mPFC and limbic structures are thought to play an important role in processing emotional memories, including fear memories, during REM sleep. The infralimbic cortex (IL) in the mPFC is thought to play a critical role in suppressing fear memories. We show that theta inputs to the IL, unlike other frequency inputs, are effective in producing synaptic changes that suppress the activity of fear expression cells associated with a given memory. Under PTSD REM sleep conditions, lower-frequency (4 Hz) theta inputs to the IL do not suppress the activity of fear expression cells associated with the given memory but, surprisingly, 10 Hz inputs do. These results suggest potential neuromodulatory therapies for PTSD.
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Analyzing functional connectivity in the brain using cross-correlation analysis of local field potentials
Measuring and analyzing local field potential (LFP) signals from basolateral amygdala (BLA), hippocampus (HPC) and medial prefrontal cortex (mPFC) may help understand how they communicate with each other during fear memory formation and extinction. In our research, we have formulated a computationally simple and noise immune instantaneous amplitude cross correlation technique which can deduce lead and lag of LFPs generated in BLA, HPC, and mPFC and the directionality of brain signals exchanged between regions. LFP signals are recorded using depth electrodes in the rat brain and cross correlation analysis is applied to theta wave signals after filtering. We found that rats resilient to traumatic conditions (based on post-stress rapid eye movement sleep (REM)) showed a decrease in LFP signal correlation in REM and non-REM (NREM) sleep cycles between BLA-HPC regions after shock training and one day post shock training compared to vulnerable rats that show stress-induced reductions in REM. It is presumed this difference in neural network behavior may be related to REM sleep differences between resilient and vulnerable rats and may provide clues to help understand how traumatic conditions are processed by the brain.
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- Award ID(s):
- 1827847
- PAR ID:
- 10550296
- Editor(s):
- Kim, Jaehwan
- Publisher / Repository:
- SPIE
- Date Published:
- ISBN:
- 9781510640092
- Page Range / eLocation ID:
- 35
- Format(s):
- Medium: X
- Location:
- Online Only, United States
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1117/12.2585176
