Abstract
Learning to associate certain contexts with threat and adapting to changing environmental contingencies by learning that such contexts are no longer associated with threat are both crucial for survival. Research over the last few decades has made considerable progress in determining the brain areas involved in the encoding, retrieval and extinction of contextual fear. These studies have identified the hippocampus and amygdala, along with the prefrontal cortex and other inter-connected brain areas, as key players in contextual fear processing. In contrast to the neural circuit basis of contextual fear, the neurochemical mechanisms involved in its regulation remain poorly understood. Dopamine is well known for its role in appetitive learning but this neurotransmitter is also important for other types of learning, including spatial and aversive memory processing. Dopamine is ideally positioned to regulate contextual fear given that the areas involved receive dopamine input and express dopamine receptors. Moreover, neuronal activity, functional connectivity and synaptic plasticity in this neural circuitry are modulated by dopamine receptor signalling. Here, we review the evidence indicating that dopamine regulates various contextual fear processes, along with the more recent studies that have begun to elucidate the brain areas and neurophysiological mechanisms involved. From a fundamental research perspective, understanding how dopamine regulates contextual fear will lead to novel insights on the neurochemical modulation of neural circuit function underlying memory processing. This research may also have translational relevance given that contextual fear conditioning and extinction also provide useful preclinical models of certain aspects of anxiety-related disorders and their treatment.
Highlights
| INTRODUCTIONContexts, predict danger is adaptive and enhances survival, as does learning that previously dangerous contexts no longer pose a threat
Learning that certain environments, or contexts, predict danger is adaptive and enhances survival, as does learning that previously dangerous contexts no longer pose a threat
Amphetamine and methylphenidate given before contextual fear conditioning have been shown to decrease freezing during retention testing, indicating that these drugs reduced foreground contextual fear conditioning (Byun et al, 2014; Calzavara et al, 2009). These findings suggest that elevated levels of synaptic dopamine result in reduced contextual fear conditioning, noradrenaline may be involved in the effect of these non-selective drugs as central noradrenaline depletion has been shown to enhance fear conditioning to background contextual cues (Selden, Everitt, & Robbins, 1991; Selden, Robbins, & Everitt, 1990)
Summary
Contexts, predict danger is adaptive and enhances survival, as does learning that previously dangerous contexts no longer pose a threat. A more recent study found that D1 receptor knockouts that underwent cued fear conditioning showed decreased freezing to the background contextual cues during retention testing, compared to wild-type controls, which did not involve an effect on shock sensitivity (Ortiz et al, 2010). D3 receptor knockouts subjected to contextual fear conditioning have been shown to express decreased freezing at retention test, compared to wild-type controls, which did not involve differences in locomotor activity (Song et al, 2018). Guarraci, Frohardt, and Kapp (1999) found that D1-like receptor antagonism in the central amygdala (CeA) before cued fear conditioning decreased freezing in response to the background contextual cues during later retention testing, an effect which was not attributable to state-dependent learning. The role of D2-like receptors in the contextual regulation of fear after extinction remains unknown
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