A VTA to Basal Amygdala Dopamine Projection Contributes to Signal Salient Somatosensory Events during Fear Learning

Abstract

The amygdala is a brain area critical for the formation of fear memories. However, the nature of the teaching signal(s) that drive plasticity in the amygdala are still under debate. Here, we use optogenetic methods to investigate the contribution of ventral tegmental area (VTA) dopamine neurons to auditory-cued fear learning in male mice. Using anterograde and retrograde labeling, we found that a sparse and relatively evenly distributed population of VTA neurons projects to the basal amygdala (BA). In vivo optrode recordings in behaving mice showed that many VTA neurons, among them putative dopamine neurons, are excited by footshocks, and acquire a response to auditory stimuli during fear learning. Combined cfos imaging and retrograde labeling in dopamine transporter (DAT) Cre mice revealed that a large majority of BA projectors (.95%) are dopamine neurons, and that BA projectors become activated by the tone-footshock pairing of fear learning protocols. Finally, silencing VTA dopamine neurons, or their axon terminals in the BA during the footshock, reduced the strength of fear memory as tested 1 d later, whereas silencing the VTA-central amygdala (CeA) projection had no effect. Thus, VTA dopamine neurons projecting to the BA contribute to fear memory formation, by coding for the saliency of the footshock event and by signaling such events to the basal amygdala.

A new “sudden fright paradigm” to explore the role of (epi)genetic modulations of the DAT gene in fear‐induced avoidance behavior

“…Though we studied mainly PFC in this article, there are other important areas involved in fear conditioning such as the amygdala; despite the evidence for a dopamine signaling role in amygdala during aversive learning, the role of dopamine neurons in aversively motivated behavior is still controversial 86 . We cannot state that slight differences in PFC of our MAT versus MIX rats are causal, but it is well known that connections between the amygdala and medial prefrontal cortex (mPFC) are crucial for both fear conditioning and extinction 87 …”

Age- and Sex-Specific Fear Conditioning Deficits in Mice Lacking Pcdh10, an Autism Associated Gene

“…There are other important players in fear memory learning as well, including BLA GABAergic interneurons (Bocchio et al, 2017). Neurotransmitters such as dopamine, noradrenaline, and acetylcholine are also important (de la Mora et al, 2010;Heath et al, 2015;Kwon et al, 2015;de Oliveira et al, 2017;Wilson and Fadel, 2017;Giustino and Maren, 2018;Brandão and Coimbra, 2019;Stubbendorff et al, 2019;Tang et al, 2020). Serotonin and glutamate influence fear memory (Walker and Davis, n.d.;Maren, 1996;Bauer, 2015;Johnson et al, 2015;Bocchio et al, 2016), as does the transcription factor CREB (cyclic AMP response element-binding protein) (Vazdarjanova and McGaugh, 1998;Bocchio et al, 2017;Ressler and Maren, 2019).…”

A New Look at the Role of Mesoamygdaloid Dopamine Neurons in Aversive Conditioning

“…Despite evidence implicating both VTA dopamine neurons and the amygdala in aversive learning though, the precise role of dopaminergic projections from the VTA to the BLA in this process remained unclear. In a recent issue of The Journal of Neuroscience, Tang et al (2020) used molecular, electrophysiological, and optogenetic techniques to elucidate the contribution of this circuit to classical fear conditioning.…”

“…First, Tang et al (2020) sought to map the VTA-to-BLA pathway, using anterograde and retrograde circuit-tracing methods. Anterograde labeling of VTA dopamine neurons revealed that, within the amygdala, these neurons primarily innervate the basal nucleus (BA) and the medial portion of the CeA.…”