Citation

Zhao J, Huynh JC, Hylin MJ, OMalley J, Perez AI, Moore AN, Dash PK. J. Neurotrauma 2018; 35(1): 149-156.

Affiliation

University of Texas Medical School, Neurobiology and Anatomy , PO Box 20708 , 6431 Fannin St, MSB 7.160 , Houston, Texas, United States , 77030 ; P.Dash@uth.tmc.edu.

Copyright

(Copyright © 2018, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2016.4898

PMID

28665166

Abstract

Epidemiology studies have found that a comorbidity exists between traumatic brain injury (TBI) and stress-related disorders. However, the anatomical and cellular bases for this association is poorly understood. An inability to extinguish the memory of a traumatic event lies at the core of many stress-related disorders. Experimental studies have shown that the medial prefrontal cortex (mPFC), especially the infralimbic (IL) cortex, is required for extinction and for storing the memory of extinction. The output from the central nucleus of amygdala projects to lateral hypothalamus, paraventricular nucleus and central grey to regulate heart rate, stress hormone release and freezing behavior, respectively. Projection neurons of the IL (layers II/III pyramidal neurons) are thought to stimulate GABAergic neurons in the amygdala, which in turn, inhibit central amygdala output and reduce fear expression. Thus, loss and/or altered morphology of projection neurons of IL as a result of a mild TBI can compromise their ability to effectively inhibit the central amygdala, allowing the original fear memory to drive behavior. Using lateral mild fluid percussion injury (mFPI) in rats, we found that mFPI did not reduce neuronal numbers in the IL but caused a significant reduction in overall dendritic spine density of both basal and apical dendrites on layer II/III pyramidal neurons. Spine numbers on layer V/VI pyramidal neurons were not significantly changed as a result of mFPI. The reduction in spine density on layer II/III pyramidal neurons we observed may diminish the efficacy of these neurons to inhibit the output of the central amygdala, thereby reducing the ability of the IL to suppress fear responses following extinction training. Consistent with this, mFPI rats display enhanced freezing behavior during and after extinction training as compared to sham-operated controls, although the ability to form contextual fear memories was not impaired. These results may have implications in stress-related disorders associated with mTBI.

Language: en

Keywords

COGNITIVE FUNCTION; LEARNING AND MEMORY; NEUROPLASTICITY; SYNAPTIC LOSS AND DEAFFERENTATION; TRAUMATIC BRAIN INJURY