Unilateral Storage of Fear Memories by the Amygdala

Blair, Hugh T.; Huynh, Virginia K.; Vaz, Vanessa T.; Van, John; Patel, Reekesh R.; Hiteshi, Amit K.; Lee, Jennie E.; Tarpley, Jason W

doi:10.1523/jneurosci.0674-05.2005

Cited by 40 publications

(50 citation statements)

References 52 publications

(66 reference statements)

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“…Relatedly, the unilateral nature of the laser stimulation may have resulted in low fear learning. This is unlikely, however, as other studies have shown that robust fear memories are formed when LA plasticity is targeted to only one LA using unilateral eyelid shock (24,25). In fact, using the same fear conditioning protocol, we also found substantial levels of fear conditioning induced by a unilateral eyelid shock US (see Fig.…”

Section: Discussionmentioning

confidence: 48%

“…S2; total n = 15 cells from four animals). We also compared the firing rate evoked by 20-Hz laser stimulation to that evoked by both constant laser illumination and to that evoked by an actual eyelid shock, which has been used as an US for fear conditioning in other studies (24,25) and by our laboratory (Discussion). Laser stimulation at 20 Hz produced significantly more action potential firing than either constant illumination or eyelid shock, whereas the latter two activated comparable levels of action potential firing (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Optical activation of lateral amygdala pyramidal cells instructs associative fear learning

Johansen¹,

Hamanaka²,

Monfils

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

270

207

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Humans and animals can learn that specific sensory cues in the environment predict aversive events through a form of associative learning termed fear conditioning. This learning occurs when the sensory cues are paired with an aversive event occuring in close temporal proximity. Activation of lateral amygdala (LA) pyramidal neurons by aversive stimuli is thought to drive the formation of these associative fear memories; yet, there have been no direct tests of this hypothesis. Here we demonstrate that viral-targeted, tissuespecific expression of the light-activated channelrhodopsin (ChR2) in LA pyramidal cells permitted optical control of LA neuronal activity. Using this approach we then paired an auditory sensory cue with optical stimulation of LA pyramidal neurons instead of an aversive stimulus. Subsequently presentation of the tone alone produced behavioral fear responses. These results demonstrate in vivo optogenetic control of LA neurons and provide compelling support for the idea that fear learning is instructed by aversive stimulus-induced activation of LA pyramidal cells.ear conditioning is a simple form of associative learning that provides a powerful model system to study associative plasticity and memory formation (1-4). During fear conditioning, a neutral stimulus [termed the conditioned stimulus (CS)], often an auditory tone, is paired repeatedly with an aversive stimulus [termed the unconditioned stimulus (US)] and animals learn that the CS predicts the occurrence of the US. When the CS is encountered after learning, animals emit a stereotyped group of adaptive responses, including behavioral freezing and associated physiological adjustments, which together are termed the fear response.The lateral nucleus of the amygdala (LA) is a site of associative plasticity, where US-evoked depolarization of LA pyramidal neurons is thought to instruct plasticity at synapses formed by CS inputs onto the same neurons (5-7). Several lines of indirect evidence support the idea that this plasticity occurs as a result of a Hebbian mechanism through which depolarization of LA pyramidal neurons by the shock US coincident with weaker activation of the same cells by auditory CS inputs results in fear learning (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). This hypothesis makes the strong prediction that pairing an auditory CS with direct activation of LA pyramidal neurons as an US should be sufficient, in the absence of a shock US, to support fear learning and memory formation. Here we tested this hypothesis by substituting the aversive US with optical stimulation (19,20) of LA pyramidal neurons during learning, and we report that physiological activation of these cells results in fear conditioning. ResultsThe light activated channelrhodopsin (ChR2) (19,20) has been used in other neural systems to activate specific cell populations and produce learning (21-23). We took advantage of this technology and targeted ChR2 to pyramidal cells by in vivo viralmediated gene transfer. We used an adeno-associated virus (AAV) to express a...

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Section: Discussionmentioning

confidence: 48%

Section: Resultsmentioning

confidence: 99%

Optical activation of lateral amygdala pyramidal cells instructs associative fear learning

Johansen¹,

Hamanaka²,

Monfils

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

270

207

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“…It may be that the contralateral medial auditory thalamic nuclei are selectively engaged when a unilateral US is presented. Evidence for unilateral neural processing with a unilateral US has been demonstrated recently for measures of fear conditioning in which a periorbital shock was used as the US (Blair et al, 2005). Fear conditioning with a bilaterally applied US such as foot shock requires the amygdala in both hemispheres, but fear conditioning with a unilateral US such as periorbital shock requires only the contralateral amygdala (Blair et al, 2005).…”

Section: Discussionmentioning

confidence: 98%

Medial auditory thalamic nuclei are necessary for eyeblink conditioning.

Halverson¹,

Freeman²

2006

Behavioral Neuroscience

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The auditory conditioned stimulus (CS) pathway that is necessary for delay eyeblink conditioning was investigated with induced lesions of the medial auditory thalamus contralateral to the trained eye in rats. Rats were given unilateral lesions of the medial auditory thalamus or a control surgery followed by twenty 100-trial sessions of delay eyeblink conditioning with a tone CS and then five sessions of delay conditioning with a light CS. Rats that had complete lesions of the contralateral medial auditory thalamic nuclei, including the medial division of the medial geniculate, suprageniculate, and posterior intralaminar nucleus, showed a severe deficit in conditioning with the tone CS. Rats with complete lesions also showed no cross-modal facilitation (savings) when switched to the light CS. The medial auditory thalamic nuclei may modulate activity in a short-latency auditory CS pathway or serve as part of a longer latency auditory CS pathway that is necessary for eyeblink conditioning. Keywordseyelid; learning; medial geniculate; posterior intralaminar nucleus; suprageniculate Pavlovian conditioning paradigms are optimal for establishing the neural structures that are necessary and sufficient for learning (Thompson, 1976). The amygdala and cerebellum have been implicated as sites of learning-induced plasticity that form associations among stimuli during fear and eyeblink conditioning, respectively (Fanselow & Poulos, 2005;Thompson, 2005). These learning centers receive converging information from both conditioned stimuli (CSs) and unconditioned stimuli (USs) to form the association that is necessary for producing a conditioned response (CR). Stimulus information is thought to be relayed to learning centers by neural pathways that are distinct for different types of CRs.Neural pathways for an auditory CS in fear-motivated conditioning include the medial division of the medial geniculate nucleus (MGm), posterior intralaminar nucleus (PIN), suprageniculate nucleus (SG), and their projections to the lateral and basolateral amygdala (Bordi & LeDoux, 1994;Campeau & Davis, 1995;Edeline & Weinberger, 1992;Gabriel, Saltwick, & Miller, 1975;LeDoux, Farb, & Ruggiero, 1990;LeDoux, Sakaguchi, & Reis, 1983;McCabe, McEchron, Green, & Schneiderman, 1993;McEchron, McCabe, Green, Llabre, & Schneiderman, 1995;Supple & Kapp, 1989). The MGm is also involved in appetitive conditioning (Birt & Olds, 1981;Olds, Disterhoft, Segal, Kornblith, & Hirsh, 1972). The medial auditory thalamic nuclei (MGm, PIN, and SG) provide CS input to the amygdala but are also activated by aversive USs (Bordi & LeDoux, 1994;Edeline & Weinberger, 1992;Lennartz & Weinberger, 1992 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript related facilitation of neuronal activity in the MGm, which might be due to convergence of CS and US inputs in the MGm (Birt & Olds, 1981;Bordi & LeDoux, 1994;Edeline & Weinberger, 1992;Gabriel et al., 1975;Lennartz & Weinberger, 1992;Love & Scott, 1969;McEchron et al., 1995;Ryugo & Weinberger, 1978;S...

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“…Similarly, the lateralization of the injury and resulting pathology may not sufficiently disrupt bilateral circuit function to elicit global cognitive deficits. Blair et al (2005) recently demonstrated unilateral conditioning of amygdala-dependent fear associations, which may be more sensitive for future detection of lateralized injury-induced dysfunction [14].…”

Section: Discussionmentioning

confidence: 99%

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Lifshitz

Witgen

Grady

2007

Behavioural Brain Research

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Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance.In a model of unilateral brain injury, we sought to test whether a single lateral fluid percussion brain injury impairs cognitive performance in conditioned fear. Brain-injured mice were evaluated for anterograde cognitive deficits, with the hypothesis that acute injury-induced impairments improve over time. Male C57BL/6J mice were brain-injured, trained at five or 27 days post-injury, and tested 48 hours later for recall of the association between the conditioned stimuli (trained context or cue) and the unconditioned stimulus (foot shock) by quantifying fear-associated freezing behavior. A significant anterograde hippocampal-dependent cognitive deficit was observed at seven days in brain-injured compared to sham. Cued fear conditioning could not detect amygdala-dependent cognitive deficits after injury and stereological estimation of amygdala neuron number corroborated this finding. The absence of injury-related freezing in a novel context substantiated injury-induced hippocampal-dependent cognitive dysfunction, rather than generalized fear. Variations in the training and testing paradigms demonstrated a cognitive deficit in consolidation, rather than acquisition or recall. By one month post-injury, cognitive function recovered in brain-injured mice. Hence, the acute injury-induced cognitive impairment may persist while transient pathophysiological sequelae are underway, and improve as global dysfunction subsides.

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Unilateral Storage of Fear Memories by the Amygdala

Cited by 40 publications

References 52 publications

Optical activation of lateral amygdala pyramidal cells instructs associative fear learning

Optical activation of lateral amygdala pyramidal cells instructs associative fear learning

Medial auditory thalamic nuclei are necessary for eyeblink conditioning.

Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

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