Year: 2005
Type: dissertation
Abstract: The brain mechanisms that underlie the process of Pavlovian fear extinction are \nintricate, controversial, and of great interest to those that study learning and memory \nphenomena. Neural mechanisms of Pavlovian extinction were evaluated with fluorodeoxy-glucose \nmetabolic mapping of mouse brain regions implicated in fear acquisition \nand extinction. Subjects were trained to show a conditioned response (CR), freezing, by \npairing a tone conditioned stimulus (CS) with a footshock unconditioned stimulus (US) \nduring acquisition, and received CS-alone presentations during extinction. Pavlov’s \noriginal hypothesis of inhibitory cortical mechanisms underlying extinction was \nsupported by our finding that frontal cortical regions were hyperactive after extinction. \nPrefrontal activity was correlated with extinction retention behavior and showed evidence \nof inhibitory coupling with other regions after extinction. Changes in other regions may \nreflect elements of the original acquisition memory even after extinction, including the \nCS (auditory system), the US (external cuneate), CS-US contiguity (hippocampus), and \nexpression of the CR (amygdala). \nFurther behavioral experiments tested individual differences in extinction learning \nin congenitally helpless rats, a selectively bred strain which shows disruptions in the \nhypothalamic-pituitary-adrenal (HPA) axis and may model genetic susceptibility to posttraumatic \nstress disorder. The involvement of corticosterone in extinction learning was \ntested through the use of metyrapone, a corticosterone synthesis inhibitor. Both \ncongenitally helpless rats and metyrapone-treated mice showed significant deficits in \nextinction behavior. \nWe propose that a functional network of mutually interactive brain regions is \nformed after Pavlovian extinction training, composed of frontal regions, auditory regions, \nhippocampus, medial thalamus, and brainstem somatosensory systems. This network \nserves to inhibit the CR while preserving the original CS-US association, and the HPA \naxis may modulate this network, as evidenced by the extinction deficits seen in both \nmetyrapone-treated and congenitally helpless subjects. This is the first time such a \nfunctional network has been demonstrated after Pavlovian extinction.
Author: Douglas W. Barrett
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1809600855