PSD-95-nNOS Coupling Regulates Contextual Fear Extinction in the Dorsal CA3
Abstract
Fear extinction depends on N-methyl-D-aspartate glutamate receptors (NMDARs) and brain-derived neurotrophic factor (BDNF) activation in the limbic system. However, postsynaptic density-95 (PSD-95) and neuronal nitric oxide synthase (nNOS) coupling, the downstream signaling of NMDARs activation, obstructs the BDNF signaling transduction. Thus, we wondered distinct roles of NMDAR activation and PSD-95-nNOS coupling on fear extinction. To explore the mechanisms, we detected protein-protein interaction using coimmunoprecipitation and measured protein expression by western blot. Contextual fear extinction induced a shift from PSD-95-nNOS to PSD-95-TrkB association in the dorsal hippocampus and c-Fos expression in the dorsal CA3. Disrupting PSD-95-nNOS coupling in the dorsal CA3 up-regulated phosphorylation of extracellular signal-regulates kinase (ERK) and BDNF, enhanced the association of BDNF-TrkB signaling with PSD-95, and promoted contextual fear extinction. Conversely, blocking NMDARs in the dorsal CA3 down-regulated BDNF expression and hindered contextual fear extinction. NMDARs activation and PSD-95-nNOS coupling play different roles in modulating contextual fear extinction in the hippocampus. Because inhibitors of PSD-95-nNO...Continue Reading
References
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Anxiety Disorders
Discover the latest research on anxiety disorders including agoraphobia, panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder here.
Amygdala: Sensory Processes
Amygdalae, nuclei clusters located in the temporal lobe of the brain, play a role in memory, emotional responses, and decision-making. Here is the latest research on sensory processes in the amygdala.