Dopamine regulation of contextual fear and associated neural circuit function

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 How to cite this article: Stubbendorff C, Stevenson CW. Dopamine regulation of contextual fear and associated neural circuit function.

1MeTIQ and olanzapine, despite their neurochemical impact, did not ameliorate performance in fear conditioning and social interaction tests in an MK-801 rat model of schizophrenia

“…4 b). There is evidence that elevated levels of synaptic DA result in reduced CFC (see review [ 58 ]). For this reason, different dopaminergic drugs have been examined for FM: bupropion (a DA and NA reuptake inhibitor) and aripiprazole (a partial D2 and 5-HT1A receptor agonist) reduce the retrieval of contextual fear; in contrast, haloperidol has no effect [ 57 , 59 , 60 ].…”

Selection of active defensive behaviors relies on extended amygdala dopamine D2 receptors

“…Although the requirement of intact DA signaling in passive defensive behaviors is undeniable 30, 31 , the mechanisms by which DA regulates these behavioral responses are far from being fully understood. Our findings demonstrating that EA D2R signaling is not required for cued and contextual threat conditioning are in line with previous work performed on constitutive or striatal-specific conditional D2R deficient mice 32, 33 , but opposite to those obtained using pharmacological approaches.…”

“…Extinction of conditioned threat is classically viewed as an active inhibitory learning, characterized by a gradual decrease of the freezing responses following repeated exposure to context- or cues-predicting threats 42, 43 . Interestingly, compelling evidence indicates that the extinction process partly relies on the activation of the mesocorticolimbic DA pathway 30, 31, 44 . Indeed, DA signals conveyed by midbrain DA neurons have been shown to be necessary for and sufficient to drive extinction 45–47 .…”

Introducing the special issue on “Proteins and Circuits in Memory”

“…Considerable progress has been made in determining the brain areas involved in the encoding, retrieval and extinction of contextual fear, whereas our knowledge on the neurochemistry remains poor. Here, Stubbendorff and Stevenson (2020) review the current evidence that suggests a role for dopamine as a neurotransmitter regulating processes in contextual fear. Many areas involved in contextual fear express dopamine receptors just as dopamine modulates neural activity and synaptic plasticity in these areas.…”