Dopamine neurons projecting to the posterior striatum reinforce avoidance of threatening stimuli

Menegas, William; Akiti, Korleki; Amo, Ryunosuke; Uchida, Naoshige; Watabe-Uchida, Mitsuko

doi:10.1038/s41593-018-0222-1

Cited by 298 publications

(389 citation statements)

References 67 publications

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“…2H,I). Second, we have not observed ramping signals in our previous studies using similar techniques (Babayan et al, 2018;Menegas et al, 2017Menegas et al, , 2018 in the absence of dynamic sensory stimuli although mice exhibited a similar pattern of anticipatory licking in these conditions.…”

Section: Experimental Design: Using Virtual Reality To Dissociate Rewmentioning

confidence: 54%

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A unified framework for dopamine signals across timescales

Kim

Malik

Mikhael

et al. 2019

Preprint

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Rapid phasic activity of midbrain dopamine neurons are thought to signal reward prediction errors (RPEs), resembling temporal difference errors used in machine learning. Recent studies describing slowly increasing dopamine signals have instead proposed that they represent state values and arise independently from somatic spiking activity. Here, we developed novel experimental paradigms using virtual reality that disambiguate RPEs from values. We examined the dopamine circuit activity at various stages including somatic spiking, axonal calcium signals, and striatal dopamine concentrations. Our results demonstrate that ramping dopamine signals are consistent with RPEs rather than value, and this ramping is observed at all the stages examined. We further show that ramping dopamine signals can be driven by a dynamic stimulus that indicates a gradual approach to a reward. We provide a unified computational understanding of rapid phasic and slowly ramping dopamine signals: dopamine neurons perform a derivative-like computation over values on a moment-by-moment basis.

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Section: Experimental Design: Using Virtual Reality To Dissociate Rewmentioning

confidence: 54%

“…We first performed fiber fluorometry (photometry) (Howe and Dombeck, 2016;Kudo et al, 1992;Lerner et al, 2015;Parker et al, 2016) to measure dopaminergic axon activity in the ventral striatum (Babayan et al, 2018;Menegas et al, 2017Menegas et al, , 2018 (Fig. 2D,E).…”

Section: Experimental Design: Using Virtual Reality To Dissociate Rewmentioning

confidence: 99%

A unified framework for dopamine signals across timescales

Kim

Malik

Mikhael

et al. 2019

Preprint

Self Cite

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“…In HD, there are several neurobiological mechanisms by which differential learning from loss and reward might arise. The indirect pathway mediates learning from loss, whereas the direct pathway mediates learning from reward . There is selective early degeneration of the indirect pathway at the level of the striatum compared with the direct pathway in HD, and apathy in HD has been correlated with altered resting‐state activity in a circuit centered on the dorsal striatum .…”

Section: Discussionmentioning

confidence: 99%

“…The indirect pathway mediates learning from loss, whereas the direct pathway mediates learning from reward. 25,28,[69][70][71][72] There is selective early degeneration of the indirect pathway at the level of the striatum compared with the direct pathway in HD, 19,26,27 and apathy in HD has been correlated with altered resting-state activity in a circuit centered on the dorsal striatum. 73 Apathy in HD has also been correlated with amygdala atrophy and hypoperfusion.…”

Section: Discussionmentioning

confidence: 99%

Insensitivity to loss predicts apathy in huntington's disease

et al. 2019

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Background Apathy is a deficit in goal‐directed behavior that significantly affects quality of life and function. It is common in Huntington's disease and other disorders affecting corticostriatal pathways. Deficits in processing of reward, altered effort, and executive dysfunction are associated with apathy in other disorders, but the cognitive processes leading to apathy in Huntington's disease remain largely unknown. A previously reported deficit in learning from losses in Huntington's disease raises the possibility of a hitherto unrecognized mechanism leading to apathy. This study's objective was to delineate the cognitive processes associated with apathy in HD. Methods We tested 51 Huntington's disease participants and 26 controls on a battery of novel and established measures to assess the contribution to apathy in Huntington's disease of executive function, reward value, reward‐effort calculations, instrumental learning, and response to reward and loss. Results Huntington's disase participants had deficits in instrumental learning with impaired response to loss, but no evidence to suggest altered reward‐related behavior or effort. We also saw an executive dysfunction contribution to apathy in Huntington's disease. Discussion We report the novel finding that apathy in Huntington's disease is associated with blunted responses to losses and impaired instrumental learning. This association is consistent with the known early degeneration of the indirect pathway and amygdala involvement in apathy in Huntington's disease, but is previously unreported in any disorder. In keeping with the comparative preservation of the ventral striatum and orbitofrontal cortex in Huntington's disease, reward valuation and reward‐effort calculations did not contribute to apathy. © 2019 International Parkinson and Movement Disorder Society

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“…57 Similarly, the activation of dopamine neurons projecting to the posterior tail of the striatum caused aversive learning. 58 Therefore, optogenetic experiments with reward and punishment learning reveal a projection-site-specific pattern of sustained effects, with phasic activation and suppression of dopamine in the NAc causing approaching and avoidance learning, respectively, and phasic activation causing avoidance learning in the PFC and in the tail of the striatum.…”

Section: Sustained Dopamine and Serotonin Effects On Behaviormentioning

confidence: 99%

Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

Yagishita

2019

Psychiatry Clin Neurosci

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Pharmacological studies of antidepressants and atypical antipsychotics have suggested a role of dopamine and serotonin signaling in depression. However, depressive symptoms and treatment effects are difficult to explain based simply on brain‐wide decrease or increase in the concentrations of these molecules. Recent animal studies using advanced neuronal manipulation and observation techniques have revealed detailed dopamine and serotonin dynamics that regulate diverse aspects of motivation‐related behavior. Dopamine and serotonin transiently modulate moment‐to‐moment behavior at timescales ranging from sub‐second to minutes and also produce persistent effects, such as reward‐related learning and stress responses that last longer than several days. Transient and sustained effects often exhibit specific roles depending on the projection sites, where distinct synaptic and cellular mechanisms are required to process the neurotransmitters for each transient and sustained timescale. Therefore, it appears that specific aspects of motivation‐related behavior are regulated by distinct synaptic and cellular mechanisms in specific brain regions that underlie the transient and sustained effects of dopamine and serotonin signaling. Recent clinical studies have implied that subjects with depressive symptoms show impaired transient and sustained signaling functions; moreover, they exhibit heterogeneity in depressive symptoms and neuronal dysfunction. Depressive symptoms may be explained by the dysfunction of each transient and sustained signaling mechanism, and distinct patterns of impairment in the relevant mechanisms may explain the heterogeneity of symptoms. Thus, detailed understanding of dopamine and serotonin signaling may provide new insight into depressive symptoms.

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Dopamine neurons projecting to the posterior striatum reinforce avoidance of threatening stimuli

Cited by 298 publications

References 67 publications

A unified framework for dopamine signals across timescales

A unified framework for dopamine signals across timescales

Insensitivity to loss predicts apathy in huntington's disease

Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

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