Hippocampal Inactivation Disrupts Contextual Retrieval of Fear Memory after Extinction

“Hippocampal activation during extinction recall is likely related to signaling the extinguished context (contextual safety; Corcoran, Desmond, Frey, & Maren, 2005; Corcoran & Maren, 2001).”

“The hippocampus also contributes to the regulation of emotion (Corcoran and Maren, 2001; Corcoran et al., 2005; Milad et al., 2007) and the structural changes in this area following mindfulness practice may reflect improved function in regulating emotional responding.”

“…62 .............................................................................................................................................. Neuropsychopharmacology REVIEWS REVIEW (ie fear was lower than controls) (Corcoran and Maren, 2001, 2004; Hobin et al, 2006).”

“A recent study indicates that the hippocampus modulates the expression of extinction memorie”

“Hippocampal inactivation 24 hours after extinction prevents contextual shifts from modulating extinction recall (Corcoran and Maren 2001).”

“ible interference with CA1 (81, 82, 160) or entorhinal”

“…hippocampus (Frohardt et al., 2000) or fimbria-fornix (Wilson et al., 1995) have no apparent effect, but pre-test hippocampal inactivation using local infusion of the GABA agonist muscimol impairs renewal (i.e., facilitates extinction retention within the test context) (Corcoran and Maren, 2001).”

“After extinction, for example, fear expression is contextually regulated, and this regulation requires the hippocampus (Corcoran and Maren, 2001).”

“Fast-spiking PVINs target the perisomatic region of pyramidal cells, thereby dictating the timing and synchronization of action potentials (Cobb et al., 1995; Freund and Katona, 2007).”

“The reinstatement of context, either from the time of acquisition or from the time of extinction, is detected by the hippocampus, which is then able to retrieve the memory for the meaning of a stimulus in that context (Corcoran & Maren, 2001; Maren et al., 1998).”

“Inactivation of the hippocampus after extinction learning prevents the renewal of conditioned fear in a non-extinction context (Corcoran and Maren, 2001, 2004; Hobin et al, 2006).”

“…by local injection of muscimol into the dorsal or ventral hippocampus prior to testing completely prevented contextdependent renewal of conditioned fear when tested in a novel context (Corcoran & Maren, 2001; Hobin et al., 2006), but not in the fear conditioning context (Corcoran & Maren, 2004).”

“…including the amygdala (Davis, 2002; Davis et al., 2003), prefrontal cortex (Milad and Quirk, 2002; Santini et al., 2004), and hippocampus (Corcoran and Maren, 2001, 2004) has been identified in mediating these processes, respectively, although functional overlap among these structures…”

“This dose has been successfully used in other recent experiments to inactivate the DH (Holt and Maren, 1999a; Corcoran and Maren, 2001).”

“, [40]), research suggests that the hippocampus is involved in contextual modulation of extinction and works in concert with the PFC during contextual extinction learning.”

“For instance, the hippocampus will activate IL to suppress fear when the CS is presented in the context in which it was extinguished (Corcoran and Maren, 2001).”

“Although considerable data indicate an important role for the hippocampus in the renewal of extinguished fear (Corcoran and Maren, 2001; Corcoran et al., 2005; Hobin et al., 2006; Maren, 2011), we now show for the first time that the PL has an important role in this process.”

“One factor that might account for this discrepancy is that Corcoran and Maren (2001) used an ABC renewal design (Experiment 2), whereas Bouton and colleagues used an ABA design (Wilson et al., 1995; Frohardt et al., 2000).”

“In contrast to Bouton’s findings, Maren and colleagues (Corcoran and Maren 2001, 2004; Corcoran et al. 2005; Ji and Maren 2005; Hobin et al. 2006) report that context-specific extinction does require a contribution of the hippocampal formation.”

“…Broom-ing (Anagnostaras et al., 2001) and extinction of a disfield, CO), which employed a multidimensional window discriminatorcrete CS (Corcoran and Maren, 2001), but does not afto select units based on waveform parameters such as peak-to-fect the acquisition of a simple CS-US…”

“[16]).”

“Indeed, dorsal hippocampal lesions and inactivations after extinction training prevent the contextdependent renewal of conditioned fear [37,38].”

“The procedures have been described in detail [49].”

“Moreover, as has recently also been recognized in the context of research concerned with the role of the hippocampus in classical fear conditioning (Anagnostaras et al., 2001, 2002; Bast et al., 2001b; Corcoran and Maren, 2001), problems like secondary changes and recovery of function may confound the interpretation o…”

“…of European Neuroscience Societies and Blackwell Publishing Ltd European Journal of Neuroscience, 24, 1751–1758 extinction learning causes increased freezing the following day (Corcoran et al., 2005) but inactivating prior to extinction recall decreases freezing (Corcoran & Maren, 2001, 2004).”

“That is, muscimol-treated animals continued to exhibit high levels of freezing to the tone irrespective of the context they were tested in (Corcoran et al, 2005; Corcoran and Maren, 2001; Hobin et al, 2006).”

“Previous studies by this group indicated that Neuropsychopharmacology treating the dorsal hippocampus with muscimol produced selective impairment in the context specificity of extinction (Corcoran and Maren, 2001).”

“Further, they show that the actual level of retrieval performance in the first test is not crucial for extinction; probably the essential element is merely the detection of the CS–“no shock” association (Konorski, 1948; Pavlov, 1956; Corcoran and Maren, 2001).”

“The hippocampus is involved in contextual modulation of retrieval/expression of extinction (Corcoran and Maren, 2001; 2004; Hobin et al., 2006), but it is not yet known if manipulations of hippocampal activity during the acquisition of extinction could later reduce the context-specificity of extinction expression.”

“As expected (Corcoran and Maren, 2001, 2004; Hobin et al., 2003; Ji and Maren, 2005), experiment 1 shows that saline-infused rats tested to a CS outside the extinction context freeze more than rats tested inside an extinction context.”

“An important study conditioned rats in one context and conducted extinction training in a different context (Corcoran & Maren, 2001).”

“A role for hippocampus, an area long thought to be involved in context learning [58] is also suggested by data indicating that the ABC renewal effect is suppressed by inactivation of the hippocampus [59], although the ABA renewal effect is not affected by lesions [60,61].”

“The same concentration of muscimol has been infused in other brain regions to examine its effect on learning and memory (Corcoran & Maren, 2001; Souza et al., 2002).”

“If an extinguished CS is presented in a context that is inconsistent with the extinction context, conditioned fear returns; a phenomenon referred to as fear renewal (Corcoran and Maren 2001, 2004; Rothbaum and Davis 2003; Bouton et al. 2006).”

“Once extinguished, however, memory for the CS becomes context specific (Bouton and Bolles, 1979; Harris et al., 2000; Corcoran and Maren, 2001); that is, the decrement in the CR that occurs during extinction training is only evident when animals are tested in the extinction context.”

“…et al. 1995; Frohardt et al. 2000) found no role for the hippocampus in renewal after making permanent lesions in an ABA renewal design, whereas our previous data (Corcoran and Maren 2001) suggested a role for the hippocampus after temporary hippocampal inactivation in an ABC renewal design.”

“…temporary inactivation of the hippocampus before an extinction retention test block renewal of extinguished freezing when that test occurs outside of the extinction training context (Corcoran et al, 2005; Corcoran and Maren, 2001, 2004; Hobin et al, 2006; Ji and Maren, 2008; Maren and Hobin, 2007).”

“…experiments using intrahippocampal muscimol infusions that the dorsal hippocampus (DH) plays an important role in the context-dependent retrieval of fear memory in two different Pavlovian interference paradigms: latent inhibition (Holt and Maren 1999) and extinction (Corcoran and Maren 2001, 2004).”

“It is suggested that acquisition and extinction may share some common mechanisms ( Corcoran and Maren , 2001 ; Vianna et al .”

“For example, the hippocampus is known to be involved in the contextual modulation of extinction (Corcoran and Maren 2001, 2004; Hobin et al. 2006), but it is not yet known if manipulations of hippocampal activity during the acquisition of extinction could later reduce the context specificity of…”

“…studies have investigated the neuroanatomy of memory processing and have identified the hippocampus, a medial temporal structure in the limbic system, as a primary structure involved in memory processing and contextual learning (Corcoran & Maren, 2001; Eichenbaum, 2000; Squire & Zola-Morgan, 1991).”

“The hippocampus (HC) is critical for forming an array of memories, including spatial associations (Anagnostaras, Gale, & Fanselow, 2001; Corcoran & Maren, 2001; Frohardt, Guarraci, & Figure 3.”

“Over the past decades, studies on the neurobiological basis of fear extinction have discovered that multiple brain regions are recruited by fear extinction (Corcoran and Maren, 2001; Falls et al., 1992; Morgan et al., 1993; Vianna et al., 2001).”

“Using reversible hippocampal lesions, we have shown that the dorsal hippocampus is required for the context-specific expression of fear memory after extinction but not for the expression for extinction per se (Corcoran and Maren 2001).”

“Thus, inactivation of the dorsal hippocampus with muscimol impairs fear renewal when extinction is tested in a novel context (Corcoran and Maren, 2001).”

“Recently, several reports have shown that the hippocampus is involved in the extinction of hippocampus-dependent memories [10,11].”

“There is extensive evidence that the hippocampus is involved in the retrieval of contextual, spatial, or declarative memory and is also a primary target for stress hormones (2, 40, 41).”

“Lastly, findings also suggest that the hippocampus plays a role in mediating context-specific learning and recall of fear extinction (Corcoran & Maren, 2001, 2004).”

“This view is consistent with ample evidence in the fear-conditioning literature, which indicates that the magnitude of the conditioned fear response depends on interactions between context and the discrete CS (Bouton and Bolles, 1979; Corcoran and Maren, 2001; Bouton , 2002).”

“GABA has previously been shown to play an important role in memory registration and emotional and fear memory encoding (Corcoran & Maren, 2001).”

“Finally, both dorsal (DH) and ventral hippocampus (VH) might be involved in extinction processing (Clark et al. 1992), possibly by encoding information about contextual features of the environment where extinction occurs (Corcoran and Maren 2001).”

“…(Heuser, 1998; Korte, 2001; Vermetten and Bremner, 2002b; Kaufer et al., 2004; Charney and Manji, 2004; de Kloet et al., 2005), may accelerate processes involved in the extinction of traumatic memories (Corcoran and Maren, 2001; Lin et al., 2003; Debiec and LeDoux, 2004; Maren and Quirk, 2004).”

“Although muscimol infusions have been utilized by numerous investigators [16,17], a recent study demonstrated that anxiety is reduced following prefrontal muscimol infusions in nonconditioned animals without having any effect on the cardiovascular stress response [18].”

“For example, hippocampal dysfunction during or after extinction training has been shown to disrupt the context-dependent expression of the ‘CS–no US’ memory (Corcoran, Desmond, Frey, & Maren, 2005; Corcoran & Maren, 2001, 2004; Ji & Maren, 2005).”