Psychotherapy and Neuroscience

Animal Fear Conditioning

Animal research has also been demonstrating the interplay between the hippocampus and amygdala in fear conditioning. The amygdala facilitates the acquisition of the conditioned fear response to both the conditioned stimulus (CS) and foreground context. A context is an interrelated assortment of sensory environmental cues that coexist with any given CS. The hippocampus facilitates fear conditioning learning to (peripheral) background context. Lesioning either of these structures produces reductions in freezing behaviors (Phillips & LeDoux, 1992, 1994).

Hippocampal lesion induced temporally graded retrograde amnesia also occurs during fear conditioning. Post-training lesions of the hippocampus (lesions occurring after fear conditioning training) at one day produce an early time limited learning impairment in recognizing fear-producing contexts or environments (Anagnostaras, Maren, & Fanselow, 1999). Post-training tetrodotoxin (TTX) inactivation of the hippocampus at 1.5 hours, basolateral amygdala at two days, and perirhinal cortex at 8 days disrupted fear conditioning learning and consolidation in a temporally induced manner (Sacchetti, Lorenzini, Baldi, Tassoni, & Bucherelli, 1999). Hippocampal lesions 7- 28 days after training have no effect (Kim & Fanselow, 1992). Rats receiving pretraining neurotoxic hippocampal lesions are able to acquire contextual fear conditioning freezing during the training session, one and 28 days later (Maren, Aharonov, & Fanselow, 1997). These findings correlate with those in the human with MTL damage having spared conditioning abilities (Weiskrantz & Warrington, 1979). Interestingly the same animal lesioning studies and those with amygdaloid lesions (Peinado-Manzano, 1988) document significantly increased motor activity. These findings may also be suggestive of increased striatal response learning and expression as noted earlier.

The amygdala receives auditory input and relay from the auditory thalamus and sensory cortex. It transmits fear-related information to corticohippocampal regions and arousal-related input to subcortical structures (LeDoux, 1998). With discrete lesioning of its lateral nucleus, behavioral freezing deficits have been noted to fear producing contexts and to the unpaired CS due to disruptions in the US-CS association (Goosen & Maren, 2001; Nader, Majidishad, Amorapanth, & LeDoux, 2001). The lateral nucleus normally undergoes neural changes that help the CS to take on the aversive qualities of the US during short and later term memory (Blair, Schafe, Bauer, Rodriguez, & LeDoux, 2001). According to the animal research, both the amygdala and hippocampus make important contributions to the gestalt of fear conditioning experience, i.e. the amygdala to object, source and context and the hippocampus to context alone.

The amygdala’s lateral nucleus of the amygdala also relays neural information through its projections with its central nucleus (LeDoux, 2000). The central nucleus’s projections to the brainstem modulate reactive reflexive fear responses and those for autonomic arousal and increased cardiovascular output (Carrive, 2000; Gallagher & Holland, 1994). Its lesioning impairs the acquisition of freezing behaviors (Nader et al., 2001) due to discontinuities with autonomic centers for arousal.

The formation of fear conditioning’s US-CS association also produces a 33% decrease and suppression in the number of proliferating cells (also known as neurogenesis) in the dentate gyrus of the hippocampus proper with no change in cell number (Pham, McEwen, LeDoux, & Nader, 2005). The dentate gyrus has been associated with acquisition-related orthogonal input that is needed for the development of a rapidly developing and meaningful contextual representation to support and aid retrievability (Lee & Kesner, 2004). In fact, the amygdala normally blocks hippocampal consolidation-related cellular long-term potentiation (LTP) during overwhelming, uncontrollable, and chronic stress like during rat’s tail shock and fear conditioning. Electrolytic lesions of the amygdala block this ability and allow for more normalized hippocampal LTP. Chronic stress on the other hand enhances fear conditioning learning and performance of stimulus-response strategies (Kim & Diamond, 2002; Kim, Lee, Han, & Packard, 2001). The animal research illustrates that the amygdala has a modulatory effect on the hippocampus during fear conditioning and stress.


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