Importantly, pathological anxiety was associated with excessive deployment of anticipatory physiological response as threat, but not safety, outcomes became more imminent. Multivariate network analyses of resting-state functional connectivity data from a subsample were used to identify intrinsic-function correlates of anticipatory-response dynamics, within a specific, distributed network derived from translational research on defensive responding.īy considering threat imminence, analyses revealed specific anxiety effects. Temporal changes in skin-conductance indexed anxiety effects on anticipatory responding as function of threat imminence. Insight from basic neuroscience research in animals on threat imminence could guide mechanistic research in humans mapping abnormal function in this circuitry to aberrant defensive responses in pathological anxiety.ĥ0 pediatric anxiety patients and healthy-comparisons (33 females) completed an instructed threat-anticipation task whereby cues signaled delivery of painful (threat) or non-painful (safety) thermal stimulation. Animal research indicates that threat-anticipatory defensive responses are dynamically organized by threat imminence and rely on conserved circuitry. Abbreviations are the same as in Figure 2.Įxcessive expression of fear responses in anticipation of threat occurs in anxiety, but understanding of underlying pathophysiological mechanisms is limited. This results in dendritic retraction and loss of spines in principal and granule cells (green hatching) creating exaggerated fear and impaired memory function. With chronic stress, more CRF released in both medial prefrontal cortex and hippocampus. With acute stress CRF enhances learning and augments LTP. In the middle and right panels, the effects CRF in acute and chronic stress in the medial prefrontal cortex and hippocampus are shown. In the central amygdala to BNST circuit, CRF is involved in facilitating fear to weak threatening stimuli and sustaining fear long beyond the duration of fear stimuli. CRF is excitatory and infusions induce hyperexcitability in PNs with exaggerated fear, enhanced fear learning, and late onset seizures. The left panel has two schematic drawings of CRF in the basolateral amygdala on the left and the lateral division of central amygdala CRF pathway (CeAL CRF +) projecting to the BNST on the right. CRF neurons are illustrated by red cells and the small red circles depict volume conduction of CRF molecules to dendrites of PN and GC dendrites. | Kindling, Fear, and Acute and Chronic Stress: CRF.
Abbreviations are the same as in Figure 2. Function of the hippocampus is altered leading to impairment of trace and context fear conditioning. There is a mix of dendritic retraction, loss of spines, and an increase in axonal grow in granule cells (green hatching). However, during late amygdala-kindling (∼100 stimulations), somatostatin interneurons die, and spontaneous seizures develop. The strong inhibition reduces the spread of kindled seizures, but trace and context fear conditioning persist. During early phases, kindling induces an increase in the number of somatostatin interneurons is induced which strongly inhibits dendritic activity. In the middle and right panels, the effects of early and late amygdala kindling in the dentate gyrus are shown. This results in exaggerated fear but also an impairment in fear conditioning. This releases the glutamatergic principal neurons from strong dendritic inhibition and inhibition at the soma to increase activity of these neurons. In the basolateral amygdala in the left panel, kindling produces a loss of somatostatin interneurons (blue stippling).
Simplified schematic drawing of the effects of amygdala kindling on somatostatin.
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