Brief uncontrollable stress causes dendritic retraction in infralimbic cortex and resistance to fear extinction in mice - PubMed (original) (raw)

Brief uncontrollable stress causes dendritic retraction in infralimbic cortex and resistance to fear extinction in mice

Alicia Izquierdo et al. J Neurosci. 2006.

Abstract

Extinction of conditioned fear responses is an active learning process resulting from the repeated presentation of a conditioned stimulus in the absence of the unconditioned aversive stimulus. Recent research implicates the medial prefrontal cortex (mPFC) in the mediation of fear extinction in rodents and the pathophysiology of posttraumatic stress disorder. However, there is currently little understanding of precisely how stress can impact fear extinction and the neural circuitry subserving this behavior. The present study examined the effects of brief exposure to an uncontrollable stressor on (1) fear conditioning and fear extinction, and (2) dendritic morphology of pyramidal neurons in the infralimbic (IL) and prelimbic (PL) regions of the mPFC in mice. Exposure to three episodes of stress ending 24 h before fear conditioning significantly attenuated the rate of cued fear extinction relative to nonstressed controls, but did not affect fear conditioning or cue or context recall. Analysis of Golgi-stained neurons showed that one or three exposures to daily swim stress caused significant retraction of terminal branches of apical, but not basilar, dendrites of IL neurons. In contrast, PL neuronal morphology was unaltered by stress. These data demonstrate that IL, but not PL, neurons are highly sensitive to even brief exposure to stress, and that this same form of stress impairs fear extinction. Present findings suggest that trauma may compromise the functional integrity of the mPFC with implications for the pathophysiology of certain neuropsychiatric disorders.

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Figures

Figure 1.

Figure 1.

Uncontrollable stress causes deficits in fear extinction. A, Schematic depiction of the behavioral testing procedure. B, Stress significantly increased freezing during extinction training but did not affect fear acquisition or initial recall of the conditioned tone. C, Stress significantly increased the number of trials to extinction criterion (n = 10–11/stress condition). Data in Figures 1–3 are means ± SEM. *p < 0.05 versus zero stress.

Figure 2.

Figure 2.

Uncontrollable stress rapidly causes retraction of apical dendrites in IL pyramidal neurons. A, Golgi-stained IL pyramidal neuron from an unstressed mouse. B, Computer-assisted reconstructions of representative IL pyramidal neurons in mice exposed to zero, one, or three episodes of stress. C, D, Overall (C) and terminal (D) branch length, but not number, of apical dendrites were significantly reduced after one or three stress exposures relative to zero stress controls. E, F, Stress did not affect overall (E) or terminal (F) basilar branch number or length (n = 6/stress condition). Scale bar, 50 μm. *p < 0.05 versus zero stress.

Figure 3.

Figure 3.

Uncontrollable stress does not alter dendritic morphology of PL pyramidal neurons. A, Golgi-stained PL pyramidal neuron from an unstressed mouse. B, Computer-assisted reconstructions of representative PL pyramidal neurons in mice exposed to zero, one, or three episodes of stress. Scale bars, 50 μm. C–F, Stress did not affect overall or terminal branch number or length of apical (C, D) or basilar (E, F) dendrites (n = 6/stress condition).

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