Similarly, NO-EXT rats were divided into rats that were tested in Context B first and tested in Context C last (B/C) and those that were tested in Context C first and Context B last (C/B)

Similarly, NO-EXT rats were divided into rats that were tested in Context B first and tested in Context C last (B/C) and those that were tested in Context C first and Context B last (C/B). == Rabbit Polyclonal to MMP-19 Figure 1. rats were also tested in each context, but were never extinguished. We assessedArcmRNA expression within the basal amygdala (BA), lateral amygdala (LA), ventral hippocampus (VH), prelimbic cortex (PL) and infralimbic cortex (IL). We observed that the sequential retention tests induced context-dependent patterns ofArcexpression in the BA, LA, and IL of extinguished rats; Lynestrenol this was not observed in non-extinguished controls. In general, non-extinguished animals had proportionately greater numbers of non-selective (double-labeled) neurons than extinguished animals. Lynestrenol Collectively, these findings suggest that extinction learning results in pattern separation, particularly within the BA, in which unique neuronal ensembles represent fear memories Lynestrenol after extinction. Keywords:amygdala, prefrontal cortex, hippocampus,Arc, renewal, context, extinction, fear == Introduction == The extinction of conditioned fear has direct parallels with cognitive-behavioral treatments, such as exposure therapy, for anxiety disorders in humans (Bouton,1988; Zinbarg et al.,1992; Rothbaum and Schwartz,2002; Mineka and Oehlberg,2008). During extinction, a previously conditioned stimulus (CS) is repeatedly presented without the unconditioned stimulus (US; Pavlov,1927), resulting in a decrease in learned fear behavior, often measured as freezing. Importantly, extinction does not erase the original fear memory; instead, it creates an inhibitory memory that suppresses fear (Pavlov,1927; Bouton,1993; Maren,2011). The inhibitory memory is context-dependent insofar as fear will renew if the CS is presented in a different context (Bouton and Bolles,1979). This indicates that contextual cues modulate the retrieval of extinguished fear memories, leading to the expression or suppression of fear to the CS in the renewal or extinction contexts, respectively. Contextual regulation of extinction is mediated by a brain circuit involving the hippocampus, prefrontal cortex (PFC) and amygdala (Maren and Quirk,2004; Herry et al.,2008; Maren,2011; Orsini et al.,2011). For example, the renewal of fear involves hippocampal projections to both PFC and the basal amygdala (BA). Inactivation of the hippocampus disrupts context-dependent firing in the amygdala (Maren and Hobin,2007) and the elimination of hippocampal input to the BA either directly or indirectly via the prelimbic area (PL) of the PFC disrupts renewal (Orsini et al.,2011). Moreover, fear renewal is associated withFosexpression in PL and BA, whereas fear suppression yieldsFosexpression in the infralimbic cortex (IL) of the PFC and inhibitory intercalated cells (ITC) in the amygdala (Knapska and Maren,2009). These findings suggest a circuit model in which structures upstream of the BA, including the hippocampus and PFC, sculpt its activity to produce context-dependent fear behavior. Though the circuitry underlying the contextual modulation of fear is fairly well understood, it is less clear how neuronal networks in the hippocampus, PFC, and amygdala represent extinguished CSs. Neurophysiological recordings in the BA suggest that two separate populations of CS-responsive neurons are engaged during either the renewal or suppression of fear (Herry et al.,2008). However, it is not known whether similar cell assemblies exist in the PFC and hippocampus and whether these brain areas differ with regards to the number of neurons responding in a context-dependent manner. To address these questions, the present study used cellular compartment analysis of temporal activity by fluorescentin situhybridization (catFISH) to visualize neuronal activation to two different behavioral experiences (Guzowski and Worley,2001). Here, we use the cellular distribution ofArcmRNA to characterize neuronal ensembles in the PFC, hippocampus and amygdala that are engaged during the retrieval of fear and extinction memories. == Materials and Methods == == Subjects == Experimental subjects were male Long-Evans rats (200224 g; Blue Spruce) obtained from a commercial supplier (Harlan Sprague-Dawley, Indianapolis, IN). Rats were housed individually in clear plastic hanging cages and were maintained on a 14:10 light:dark cycle with access to food and waterad libitum. Prior to the start of the experiment, rats were handled 1520 s/day for 5 continuous days so as to acclimate the animals to the experimenter. All experimental procedures were carried out in accordance with the protocols approved by the University of Michigan Committee on the Use and Care of Animals (UCUCA). == Behavioral apparatus == All behavioral sessions occurred in eight identical observation chambers (30 24 21 cm; Med-Associates, St. Albans, VT), constructed of a Plexiglas ceiling, back and door and two aluminum sidewalls. The floor of each observation chamber consisted of 19 stainless steel rods (4 mm in diameter) by which the footshock US was delivered. The rods of the floor were wired to a shock source and a solid-state shock scrambler (Med-Associates, St. Albans, VT). Within each observation chamber, a speaker was mounted on one sidewall to deliver the acoustic CS. Lastly, each chamber contained a house light and ventilation fans that could be manipulated to create distinct.