Indistinguishable pattern of amygdala and hippocampus rewiring following tone or contextual fear conditioning in C57BL/6 mice (original) (raw)
The Amygdala and Fear Conditioning: Has the Nut Been Cracked?
Neuron, 1996
portantly, loss of fear. Later work indicated that the reduced fear in resected monkeys was due specifically Los Angeles, California 90095 to damage in the amygdala. Consistent with its general role in fear, reports began to emerge that the amygdala was also required for aversive learning, including the Pavlovian fear conditioning is a ubiquitous form of learnacquisition of conditioned avoidance responses in cats ing that involves the association of stimuli and their and conditioned emotional responses in rats. Together, aversive consequences. Perhaps the quintessential exthese reports provided a strong foundation for amygample of Pavlovian fear conditioning is Watson and daloid involvement in fear and aversively motivated Rayner's (1920) experiment with "Little Albert." In this learning. experiment, Albert, a normal and healthy child attending Building upon this foundation, considerable progress day care, was shown a white rat by Rayner. Not surprishas been made in the last decade further defining the ingly, Albert's first reaction to the white rat was curiosity, anatomy of the amygdaloid fear system (Figure 1). It is and when presented with the rat he reached out to touch now apparent that within the amygdala there are two it. In response to Albert's attempt to touch the rat, Watsubsystems that have unique roles with regard to fear son, who had been closely observing Albert's interaction conditioning (Davis et al., 1994; Fanselow, 1994; Lewith the rat, sounded a loud and frightening noise by Doux, 1995). The basolateral complex of the amygdala hammering an iron rail. Albert, startled and scared by the (BLA; comprised of the lateral [LA], basolateral [BL], noise, quickly withdrew from the rat and began crying. and basomedial [BM] nuclei) is a substrate for sensory Watson and Rayner continued the procedure, and after convergence from both cortical and subcortical areas, a few more presentations of the white rat followed by and is considered a putative locus for CS-US associanoise, Albert began to show an intense fear of the rat. tion during fear conditioning. In contrast, the central Evidently, Albert had associated the frightening noise nucleus of the amygdala (CE), which receives projecwith the white rat. Indeed, Little Albert had been conditions from the BLA, projects to brain areas involved in tioned to fear white rats! the generation of fear responses, such as the lateral In recent years, the process by which the brain medihypothalamus (LH) and periaqueductal gray (PAG). It is ates Pavlovian fear conditioning has come under intense therefore thought to be a final common output pathway examination. In the laboratory, Pavlovian fear conditionfor the generation of fear CRs. Consistent with these ing is typically studied in the object of Albert's fear, the roles, destruction of neurons in either the BLA or CE is rat. In this model, rats receive pairings of an innocuous detrimental to both the acquisition and expression of conditioned stimulus (CS), such as a tone or the context conditional fear (Campeau and Davis, 1995; Maren et of the conditioning chamber, and a noxious uncondial., 1996), regardless of the exact stimuli used to train tioned stimulus (US), such as a footshock. After a few fear or the response measure used to assess it. Thus, such pairings, the CS comes to elicit a constellation of the amygdala is ideally situated to both integrate and conditioned responses (CRs) that are characteristic of associate sensory information and to execute motor fear, including changes in heart rate and arterial blood programs during fear conditioning. pressure, somatomotor immobility (freezing), hypoalge-Associative Neuronal Firing sia, potentiated acoustic startle, and pupillary dilation. in the Amygdala In this minireview, we will present recent work that has It has been known for years that amygdaloid neurons advanced our understanding of the basic neurobiologirespond to conditional reinforcers. However, the recent cal mechanisms involved in fear conditioning. This work delineation of the amygdaloid circuits underlying fear includes the elucidation of anatomical circuits underlyconditioning has opened the door for fine-grained studing fear conditioning, the characterization of neuronal ies of physiological plasticity in these circuits during and synaptic plasticity in fear conditioning circuits, and learning. For example, investigations of neuronal firing the analysis of humans with damage in brain structures in the amygdala during aversive learning using multiplerequired for fear conditioning. Altogether, it has become unit recording techniques have revealed learningapparent that neurons in the amygdala, an almondinduced changes in both the CE (Applegate et al., 1982) shaped group of nuclei buried deep within the temporal and BL (Maren et al., 1991). In both cases, neuronal lobes, are critical for Pavlovian fear conditioning. Hence, discharges were significantly greater to an auditory CS it is the amygdala that is likely to have been responsible that was paired with a shock US than those to a different for Little Albert's fear of rats. CS that was not paired with shock. Neuroanatomy of Fear Although neuronal discrimination suggests that the Although the neural substrates of fear conditioning have changes in neuronal firing in the amygdala were associa-received considerable attention in the last decade, they tive in nature, it is not clear whether the associative have been under study for over 50 years. Perhaps the activity was generated at the recording site or relayed first clues to the neural substrates of fear came from the from an afferent region. Indeed, within the amygdala, studies of Kluver and Bucy (1937). These investigators found that temporal lobe resections in monkeys pro-the first locus of convergence for auditory CSs and footshock USs is in the LA. In recent experiments, duced an eclectic deficit, appropriately termed the
Learning & Memory, 2009
There is no clear identification of the neurons involved in fear conditioning in the amygdala. To search for these neurons, we have used a genetic approach, the fos-tau-lacZ (FTL) mouse, to map functionally activated expression in neurons following contextual fear conditioning. We have identified a discrete population of neurons in the lateral amygdala that are activated specifically following learning. These neurons have the morphology of principal neurons of the amygdala, and are immunoreactive for glutamate. The highly specific localization of these neurons within the lateral amygdala suggests that these neurons may be a discrete population of neurons involved in fear learning.
Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning
Cognitive Affective Behavioral Neuroscience, 2004
In Pavlovian fear conditioning, a neutral stimulus (conditional stimulus, or CS), usually a light or tone, is typically paired with an aversive stimulus (unconditional stimulus, or UCS) such as an electric shock. Animals learn that the CS predicts the UCS as the stimuli are repeatedly paired, and this learning is manifested as changes in behavioral and autonomic responses (Rescorla, 1988). Presentation of the CS alone provokes the expression of a conditional fear response once learning has occurred. The thalamus, hippocampus, and sensory cortex each contribute to conditional response (CR) acquisition, and the amygdala is a principal site of CS-UCS convergence and critical synaptic plasticity