Glutamate receptor antagonist infusions into the basolateral and medial amygdala reveal differential contributions to olfactory vs. context fear conditioning and expression

Abstract

The basolateral amygdala's involvement in fear acquisition and expression to visual and auditory stimuli is well known. The involvement of the basolateral and other amygdala areas in fear acquisition and expression to stimuli of other modalities is less certain. We evaluated the contribution of the basolateral and medial amygdala to olfactory and to context fear and fear conditioning by infusing into these areas the NMDA receptor antagonist AP5, the AMPA/kainate receptor antagonist NBQX, or vehicle prior to either odor-shock pairings or fear-potentiated startle testing. Pre-training AP5 infusions into the basolateral amygdala disrupted fear conditioning to the odor but not the context conditioned stimulus (CS). Pre-test NBQX infusions disrupted fear-potentiated startle to the odor but not context CS. Neither compound blocked fear conditioning when infused into the medial amygdala prior to training, but pre-test NBQX infusions did block fear-potentiated startle. The results confirm and extend recent findings suggesting a role for the basolateral amygdala in olfactory fear and fear conditioning, reveal an unexpected dissociation of the basolateral amygdala's involvement in discrete cue versus context fear and fear conditioning, and implicate for the first time the medial amygdala in fear-potentiated startle.For auditory and visual stimuli, the amygdala plays a key role in fear conditioning and fear expression as assessed with several behavioral measures (cf., Fendt and Fanselow 1999;Davis 2000;LeDoux 2000). We have found, for example, that pre-test infusions into the basolateral amygdala (i.e., the lateral, basolateral, and basomedial nuclei) of ␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonists block fear-potentiated startle to visual and auditory conditioned fear stimuli (CSs), and that pre-training (i.e., light-shock or toneshock) infusions of either N-methyl-D-aspartate (NMDA) receptor antagonists or AMPA/kainate receptor antagonists block fear conditioning (cf., Walker and Davis 2002b). In most (e.g., Miserendino et al. 1990;Campeau et al. 1992;Gewirtz and Davis 1997), but not all (e.g., Fendt 2001; see also Lee et al. 2001) cases, pre-test intra-amygdala infusions of NMDA receptor antagonists have not been found to disrupt fear expression to auditory and visual CSs. Similar results have been obtained from other laboratories using different treatments and other fear-related behaviors (e.g., LeDoux et al. 1990;Muller et al. 1997;Groenink et al. 2000;Rodrigues et al. 2001).Visual and auditory information reach the basolateral amygdala indirectly via intermediary structures such as auditory and visual thalamus and perirhinal cortex. Olfactory information also reaches the basolateral amygdala indirectly. Uniquely, however, the main and accessory olfactory bulbs also send direct projections to several amygdala areas including the medial and cortical nuclei, the nucleus of the lateral olfactory tract, and the periamygdaloid cortex (cf., Alheid et al. 1995;McDonald 1998;Pitkanen...

Effects of Substance P in the Amygdala, Ventromedial Hypothalamus, and Periaqueductal Gray on Fear-Potentiated Startle

“…Although there are reciprocal connections between the BLA and MeA (Pitkanen et al, 1997), the fact that sensory inputs converge in the BLA but not in the MeA (Jolkkonen et al, 2001;LeDoux, 2000;Shi and Davis, 2001) suggests that, for fear expression, the MeA may function primarily as an output structure that responds to fear-related signals arriving from the BLA. Our previous findings that pretraining infusions of NBQX into the BLA, but not into the MeA, blocked fear learning, whereas pretest infusions into both structures blocked fear expression are consistent with this view (Walker et al, 2005). Given that BLA projection neurons are largely glutamatergic (Smith and Pare, 1994) and that there are few SP-containing neurons in the BLA (Ribeiro-da-Silva and Hokfelt, 2000; Roberts et al, 1982), it is reasonable to assume that neurotransmission between the BLA and the MeA is primarily glutamatergic, and not tachykininergic.…”

“…Fear-potentiated startle is mediated by the CeA and its projection to the deep layers of the superior colliculus/deep mesencephalic nucleus (dSC/DpMe) of the rostral midbrain and, subsequently, to the primary startle reflex circuit in the brain stem Hitchcock and Davis, 1991;Meloni and Davis, 1999;Rosen et al, 1991;Frankland and Yeomans, 1995;Zhao and Davis, 2004). In addition, we recently reported that fear-potentiated startle is also blocked by infusion of the AMPA receptor antagonist NBQX into the MeA (Walker et al, 2005). It is unclear how the MeA influences fear-potentiated startle as it does not project directly to the startle reflex circuit, the dSC/DpMe, or the CeA (Canteras et al, 1995).…”

Differential involvement of amygdala and cortical NMDA receptors activation upon encoding in odor fear memory

“…Taken together these data suggest that after the first pairing, NMDA receptors are no more involved in the processing of the next pairings or in consolidation processes, comforting our previous data showing an increase in glutamate release in BLA for the first pairing but not for the next ones (Hegoburu et al 2009). This observation is in line with previous studies showing that intra amygdala injections of NMDA antagonists carried out post-training (Maren et al 1996;Walker and Davis 2002) or before testing (Rodrigues et al 2001;Walker et al 2005 in odor fear conditioning) have no effect on consolidation and expression of auditory fear conditioning. However, it is well known that the BLA is involved in memory processes occurring during or just after training and at testing (for review, see Fanselow and Gale 2003).…”

NMDA receptor in conditioned flavor-taste preference learning: Blockade by MK-801 and enhancement by D-cycloserine

“…APV infused into the prefrontal cortex (but not hippocampus) impaired memory of an odor-food reward association when infused in the prefrontal cortex (Tronel and Sara, 2003). APV infused into the basolateral amygdala disrupted learning in taste-potentiated odor-LiCl aversion (Ferry and Di Scala, 2000;Hatfield and Gallagher, 1995) and in odor-footshock fear conditioning (Walker et al, 2005).…”