Functional inactivation of the lateral and basal nuclei of the amygdala by muscimol infusion prevents fear conditioning to an explicit conditioned stimulus and to contextual stimuli.

“Moreover, lesions of the LA, but not of the BLA, accessory basal, or medial nucleus of the amygdala block auditory-cue conditioning (Nader et al. 2001).”

“In amygdala, reduced inhibitory activity is typically associated with enhanced LTP, which is thought to facilitate fear conditioning (Muller et al., 1997; Wilensky et al., 1999).”

“Inactivation of the amygdala would produce a general reduction of freezing responses (Muller et al., 1997).”

“Because our intra-amygdalar MUSC infusion parameters are similar to those used in previous fear-conditioning studies (Helmstetter and Bellgowan, 1994;Muller et al., 1997;Wilensky et al., 1999;Maren et al., 2001;Wilensky et al., 2006) the extent of MUSC diffusion in the amygdala should be comparable.”

“…to its role in contextual fear learning and memory, based on a wealth of rodent behavioral studies (KimandFanselow, 1992; Phillips and LeDoux, 1992; Muller et al., 1997; Rosen et al., 1998; Anagnostaras et al., 1999; Goosens and Maren, 2001; Hall et al., 2001; Anglada-FigueroaandQuirk,…”

“The amygdala is particularly responsive to fear-evoking stimuli, and it appears to be the site where fear-related memories are consolidated and stored (Gale et al. 2004; LeDoux 2003, 2005; Muller et al. 1997; Pape and Pare 2010).”

“…behaviors (Davis and Walker, 2013; Felix-Ortiz et al., 2013; Tye et al., 2011) and is involved in the acquisition and expression of appetitive and aversive associative memories (Amano et al., 2011; Ambroggi et al., 2008; Muller et al., 1997; Sierra-Mercado et al., 2011; Stuber et al., 2011).”

“One current issue concerns whether the amygdala is a key site of associative plasticity for behavioral acquisition or only for the behavioral expression of plasticity (Miserendino et al., 1990; Helmstetter and Bellgowan, 1994; Muller et al., 1997; Quirk et al., 1997).”

“This was an expected result, as there is strong evidence that the BA is critical for contextual fear conditioning (Muller et al. 1997; Goosens and Maren 2001; Vlachos et al. 2011).”

“Moreover, previous studies report that the infusion of benzodiazepines or GABAA agonists in the BLA reduce anxiety (Muller et al, 1997; Scheel-Kruger and Petersen, 1982), whereas the GABAA antagonists increase anxiety(Hajizadeh Moghaddam et al, 2008); as a result, we used the GABAA receptor…”

“For example, inactivation or permanent lesions of the amygdala (Maren et al., 1996; Muller et al., 1997; Maren, 1999;Wilensky et al., 1999, 2000; Goosens and Maren, 2001; Koo et al., 2004) or hippocampus (Maren and Fanselow, 1997; Maren et al.”

“Adult male rats were conditioned as described previously (Muller et al., 1997).”

“The basolateral nucleus of the amygdala (BLA) plays an essential role in fear conditioning (Helmstetter & Bellgowan, 1994; Maren & Fanselow, 1996; Muller et al., 1997; Cahill & McGaugh, 1998; Vazdarjanova & McGaugh, 1998; Fanselow & LeDoux, 1999; Maren, 1999a,b; LeDoux, 2000; McGaugh, 2000, 2002,…”

“Consequently, intraamygdaloid AP-5 impairs fearconditioning only if infused before, but not after training (Maren et al. 1996; Muller et al. 1997) and muscimol-induced inhibition of the BLA affects fear memory formation before, but not after training (Wilensky et al.”

“In fact, both acquisition and retention of fear conditioning occur in the lateral nucleus, where electrolytic and excitotoxic lesions, as well as pharmacological blockade, prevent acquisition and expression of fear conditioning (Campeau and Davis, 1995; Muller et al., 1997; LeDoux, 2000; Gale et al., 2004).”

“4; Hitchcock and Davis 1986; Helmstetter and Bellgowan 1994; Muller et al. 1997).”

“…neurotransmitter systems and can be modulated by direct manipulation of glutamatergic (Fanselow and Kim, 1994; Sajdyk and Shekhar, 1997), GABAergic (Muller et al., 1997; Sanders and Shekhar, 1995), catecholaminergic (Gonzalez et al., 1996; Guarraci et al., 1999), and neuropeptide (Gutman et al.,…”

“For example, fear conditioning is prevented through intra-amygdalar application of GABA mimetics, while facilitated ISSN 1601-1848 65 through GABA antagonists (Fanselow & Kim 1992; Muller et al. 1997).”

“Extensive studies have shown that the lateral and basolateral amygdala play an important role in the acquisition and expression of conditioned fear (Apergis-Schoute et al. 2005; Campeau and Davis 1995; Campeau et al. 1992; Clugnet and LeDoux 1990; Josselyn et al. 2001; Liang et al. 1994; Muller et al. 1997; Sananes an…”

“The basal nucleus of the amygdala (BA) has been suggested to play an important role in contextual fear conditioning [12,13], cued fear conditioning”

“…tested this prediction by pharmacologically inhibiting the Bl, the vSub, and the cingulate/prelimbic regions of mPFC with the GABA A agonist muscimol (Izquierdo et al. 1997; Martin 1991; Muller et al. 1997) prior to testing rats for conditioned hyperactivity in a cocaine-associated environment.”

“Finally, post-training lesions or functional inactivation of amygdala also block contextual fear and consolidation of inhibitory avoidance learning (Parent and McGaugh, 1994; Wilensky et al., 2000; Muller et al., 1997; Liang et al., 1982).”

“Specifically, the basolateral (BL) complex of the amygdala (BLA), composed of basal, accessory basal, and lateral (LA) nuclei of the amygdala (16), is necessary for both acquisition and expression of conditioned freezing (17), whereas the prelimbic (PL) cortex of the mPFC, which is monosynaptically connected with the…”

“The amygdala has been suggested to be a critical structure for conditioned fear to both cues (Nader et al., 2001) and contexts (Roozendaal et al., 1993; Muller et al., 1997; Phillips and LeDoux, 1992; Antoniadis and Mc-Donald, 2000), including conditioning of the HPA axis (Roozendaal et al., 1992; Campeau et al., 1997…”

“The exposure therapy/extinction literature demonstrates a critical role played by the amygdala in fear learning (Quirk et al, 1995, 2003; Muller et al, 1997; LeDoux, 2000).”

“Nonetheless, in accordance we previous studies (Muller et al., 1997; Esclassan et al., 2009; Gilmartin and Helmstetter, 2010), we found that muscimol infusion in all three structure tended to yield lower freezing levels compared to vehicle infusion (amygdala: veh = 31.3 ± 4.1, mus = 1.6 ±…”

“Inactivation of any of these brain regions can disrupt contextual fear memory (Muller et al. 1997; Zhu et al. 2014).”

“Probe burying is thought to be a species-specific defense response emitted to focal aversive stimuli (Pinel and Treit 1978; but see Fanselow et al. 1987).”

“The lateral and basal nuclei are important for associative fear acquisition and expression, while the central nucleus is thought to be a critical relay for mediating behavioral manifestations of fear (Muller et al., 1997; Goosens and Maren, 2001).”

“…stimuli and to the explicit CS (Fanselow & Kim, 1994; LeDoux, 1993, 2000; Maren & Fanselow, 1996; Maren et al., 1996a; Maren et al., 1996b; Muller et al., 1997) but the hippocampus is thought to be required for forming an integrated (polymodal) representation of the context that would…”

“Consistent withmany previous findings, BLA lesions impaired the acquisition of CS+ freezing (Gale et al., 2004; Koo et al., 2004; Maren et al., 1996; Muller et al., 1997; Petrovich et al., 2009; Phillips and LeDoux, 1992).”

“…1996; sacchetti et al. 1999); for conflicting results see (Wilensky et al. 2000)] or prior to context re-exposure (helmstetter and Bellgowan 1994; Muller et al. 1997) attenuates freezing in the fearful context. however, no one has determined whether pre-training global inactivation of Bla will…”

“Likewise, it is not surprising that rats in the BI group failed to acquire freezing to the CS, because previous studies have shown that bilateral amygdala inactivation blocks the acquisition of auditory fear conditioning (Helmstetter and Bellgowan, 1994; Muller et al., 1997; Wilensky et al., 1999).”

“Studies on the involvement of the amygdala in fear conditioning suggest that local microinfusions into single brain areas do not interfere with learning merely on the basis of state dependency (Helmstetter and Bellgowan, 1994; Muller et al, 1997).”

“A number of studies implicate a role for GABAA receptors in the BLA in the expression of fear [29,53,57] and in the suppression of pain-related behaviour elicited by unconditioned [2,58] and conditioned [25,27,67] fear in rats.”

“Consistent with this view, laboratory studies have shown that both types of fear memory require neuronal activity in the basolateral complex of the amygdala (BLA), including activation of NMDA receptors (Campeau et al., 1992; Gewirtz and Davis, 1997; Muller et al., 1997; Fendt and Fanselow, 1999; Wilensky et al., 1999…”

“with muscimol, a treatment known to disrupt fear memory (Helmstetter and Bellgowan, 1994; Muller et al., 1997) prevents training-related neuronal activity in MGm neurons (Maren et al.”

“In addition, intra-amygdala infusion of the c-aminobutyric acid (GABA)A receptor agonist muscimol before training blocks the acquisition of conditioned fear (Muller et al., 1997; Wilensky et al., 1999).”

“In fact, inactivation of BLA neurons with a GABAA receptor agonist reduces both the acquisition and expression of fear conditioning (Helmstetter and Bellgowan, 1994; Muller et al, 1997; Wilensky et al, 1999).”

“…the γ -aminobutyric acid (GABA) agonist muscimol before conditioning impairs the acquisition of fi rst-order fear (Helmstetter and Bellgowan, 1994; Muller et al. , 1997 ; Wilensky et al. , 2006 ), but a post-conditioning infusion of muscimol does not impair retention of the fear memory…”

“The ‘baso-lateral’ nuclear group (BLNG) is the site where emotional meaning is attached to sensory cues through plasticity-dependent processes (Campeau and Davis, 1995; Huang and Kandel, 1998; LeDoux et al., 1990; Maren, 1999; Muller et al., 1997; Parkinson et al., 2000; Rogan et al., 1997).”

“Furthermore, interfering with NSF-GluR2 binding had no effect on synaptic transmission during learning which is essential for fear memory acquisition (Muller et al., 1997; Wilensky et al., 1999).”

“The BLA receives excitatory input from diverse regions of the CNS, including the thalamus (Blair et al., 2003; Muller et al., 1997; Turner and Herkenham, 1991), lateral entorhinal cortex (Mcdonald and Mascagni, 1997), hippocampus, frontal cortex (Pitkanen et al.”

“In rats, these have included muscimol [59], an NMDA-receptor antagonist [60–62], inhibitors of plasticity-related signaling molecules [63–65], and antisense oligodeoxynucleotides that interfere with gene expression [66–68].”

“These results confirm the critical role of the BLA in the expression of conditioned fear responses (Helmstetter and Bellgowan 1994; Muller et al. 1997; Lee and Kim 1998; Lee et al. 2001; Maren et al. 2001; Wilensky et al. 2006), and in learning the inhibition produced by extinction, which mediates…”

“…it has been established that the lateral, basolateral, and central nuclei are required for the acquisition and expression of conditioned freezing (Muller et al., 1997; Cousens and Otto, 1998; Nader et al., 2001; Gale et al., 2004), it is still debated which nuclei mediate unconditioned freezing…”

“Additionally, inactivation of the amygdala prior to retention testing results in significantly fewer conditioned responses (CRs), compared to controls (Muller et al., 1997).”