Differential Fear Conditioning Induces Reciprocal Changes in the Sensory Responses of Lateral Amygdala Neurons to the CS⁺ and CS⁻

Abstract

In classical fear conditioning, a neutral sensory stimulus (CS) acquires the ability to elicit fear responses after pairing to a noxious unconditioned stimulus (US). As amygdala lesions prevent the acquisition of fear responses and the lateral amygdaloid (LA) nucleus is the main input station of the amygdala for auditory afferents, the effect of auditory fear conditioning on the sensory responsiveness of LA neurons has been examined. Although conditioning was shown to increase CS-evoked LA responses, the specificity of the changes in responsiveness was not tested. Because conditioning might induce nonspecific increases in LA responses to auditory afferents, we re-examined this issue in conscious, head-restrained cats using a differential conditioning paradigm where only one of two tones (CS + but not CS − ) was paired to the US. Differential conditioning increased unit and field responses to the CS + , whereas responses to the CS − decreased. Such changes have never been observed in the amygdala except in cases where the CS − had been paired to the US before and fear responses not extinguished. This suggests that fear conditioning is not only accompanied by potentiation of amygdalopetal pathways conveying the CS + but also by the depression of sensory inputs unpaired to noxious stimuli.The amygdaloid complex is a nucleated structure of the temporal lobe receiving sensory inputs of all modalities and projecting to functionally diverse brain structures, from the highest computational levels of the brain to hypothalamic and brainstem autonomic nuclei involved in cardiovascular control and the expression of species-specific fear responses (Hopkins and Holstege 1978;Price and Amaral 1981;Bandler 1982;Veening et al. 1984;Russchen 1986;Amaral et al. 1992).Much evidence implicates the amygdala in fear learning and expression. For instance, stimulation of the central amygdaloid nucleus elicits increases in heart rate and blood pressure (Kaada 1972;Iwata et al. 1987). Moreover, amygdala lesions prevent the acquisition of classically conditioned fear responses (Kapp et al. 1979;Gentile et al. 1986;Iwata et al. 1986;Hitchcock and Davis 1987;LeDoux et al. 1990b;Killcross et al. 1997). These and other findings (for review, see Davis 1992; LeDoux 1995) have prompted investigators to search for the cellular correlates of fear learning in the amygdala.As the lateral amygdaloid (LA) nucleus is the main input station of the amygdala for auditory afferents (LeDoux et al. 1990a,b;Romanski and LeDoux 1992), a few studies have examined how auditory fear conditioning affects toneevoked LA responses (Quirk et al. 1995;Rogan et al. 1997). These studies reported that fear conditioning increases auditory-evoked responses in the LA. These changes in responsiveness were not a simple consequence of the arousal produced by the unconditioned stimulus (US) as they were not observed when the auditory conditioned stimulus (CS) and the US were presented in an unpaired manner. However, the possibility that the CS-US pairings induced nonspecific inc...

Heterosynaptic Long-Term Potentiation of Inhibitory Interneurons in the Lateral Amygdala

“…During auditory fear conditioning, CS signals from the auditory thalamus and auditory cortex converge in the LA LeDoux, 2000) and are potentiated (Quirk et al, 1995;Rogan et al, 1997;Collins and Pare, 2000;Goosens et al, 2003). In the present experiments, we examined LTP at thalamic input synapses to LA inhibitory cells.…”

“…Pavlovian auditory fear conditioning, in which a neutral conditioned stimulus (CS) such as a tone is paired with an unconditioned stimulus (US), typically a foot shock, results in longlasting changes in synaptic transmission in the lateral amygdala (LA) (Quirk et al, 1995;McKernan and Shinnick-Gallagher, 1997;Rogan et al, 1997;Collins and Pare, 2000;Repa et al, 2001). One candidate mechanism for these changes is long-term potentiation (LTP) of excitatory cells.…”

Abnormal Fear Conditioning and Amygdala Processing in an Animal Model of Autism

“…As synaptic plasticity in the LA is thought to underlie fear memories (Quirk et al, 1995;Collins and Pare, 2000;Repa et al, 2001;Bauer et al, 2002), we also tested for LTP in VPA-treated rats. We found that the potentiation caused by a classical pairing protocol with an extracellular electrode placed just medial to the LA was significantly increased in treated rats (t 12 ¼ 3.12 p ¼ 0.009; n ¼ 15 for control, 10 for treated; Figure 4c).…”

“…Synaptic plasticity is also boosted suggesting that the amygdala turned hyperplastic following a single exposure of the embryo to VPA. Considering that LTP in the basolateral amygdala is thought to be the key cellular mechanism underlying fear memory formation (Quirk et al, 1995;Rogan et al, 1997;Collins and Pare, 2000;Repa et al, 2001;Bauer et al, 2002), hyperreactivity and hyperplasticity are strong candidates mediating the enhanced and overgeneralized fear memories in the VPA-treated rats.…”

The selectivity of aversive memory reconsolidation and extinction processes depends on the initial encoding of the Pavlovian association

“…Although much of what we know about the role of the amygdala in threat conditioning comes from research using auditory cues, similar to auditory learning, the LA plays a critical role in the acquisition of visual threat conditioning (Campeau and Davis 1995;McDannald and Galarce 2011). Likewise, physiological studies of cellular responses in the LA in relation to conditioning have focused primarily on auditory stimuli (Bordi and LeDoux 1992;Romanski et al 1993;Collins and Pare 2000;Repa et al 2001;Goosens and Maren 2004;Humeau et al 2007;An et al 2012). However, some reports indicate that certain populations of cells in the LA respond both to visual and to auditory stimuli (Uwano et al 1995;Toyomitsu et al 2002;Nishijo et al 2008).…”