Dopamine enhances signal-to-noise ratio in cortical-brainstem encoding of aversive stimuli

Weele, Caitlin M. Vander; Siciliano, Cody A.; Matthews, Gillian A.; Namburi, Praneeth; Izadmehr, Ehsan M.; Espinel, Isabella C.; Nieh, Edward H.; Schut, Evelien H. S.; Padilla-Coreano, Nancy; Burgos-Robles, Anthony; Chang, Chia-Jung; Kimchi, Eyal Y.; Beyeler, Anna; Wichmann, Romy; Wildes, Craig P.; Tye, Kay M.

doi:10.1038/s41586-018-0682-1

Cited by 241 publications

(225 citation statements)

References 55 publications

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“…Additionally, in the PFC, decreased GABA A ‐stimulated chloride influx was evident in a membrane preparation from 24‐h isolated rats along with reduced benzodiazepine binding, indicating a decrease in cortical GABA A expression and/or function. Given the functional diversity of dopamine input to striatal subregions and dopamine's divergent effects on cortical projector populations, further work is necessary to elucidate precisely how these rapid isolation‐induced changes to dopamine neurotransmission influence downstream activity.…”

Section: Homeostatic Response To Social Deficit: Engaging Social Motimentioning

confidence: 99%

Neural mechanisms of social homeostasis

Matthews

Tye

2019

Annals of the New York Academy of Sciences

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154

101

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Social connections are vital to survival throughout the animal kingdom and are dynamic across the life span. There are debilitating consequences of social isolation and loneliness, and social support is increasingly a primary consideration in health care, disease prevention, and recovery. Considering social connection as an “innate need,” it is hypothesized that evolutionarily conserved neural systems underlie the maintenance of social connections: alerting the individual to their absence and coordinating effector mechanisms to restore social contact. This is reminiscent of a homeostatic system designed to maintain social connection. Here, we explore the identity of neural systems regulating “social homeostasis.” We review findings from rodent studies evaluating the rapid response to social deficit (in the form of acute social isolation) and propose that parallel, overlapping circuits are engaged to adapt to the vulnerabilities of isolation and restore social connection. By considering the neural systems regulating other homeostatic needs, such as energy and fluid balance, we discuss the potential attributes of social homeostatic circuitry. We reason that uncovering the identity of these circuits/mechanisms will facilitate our understanding of how loneliness perpetuates long‐term disease states, which we speculate may result from sustained recruitment of social homeostatic circuits.

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Section: Homeostatic Response To Social Deficit: Engaging Social Motimentioning

confidence: 99%

Neural mechanisms of social homeostasis

Matthews

Tye

2019

Annals of the New York Academy of Sciences

Self Cite

154

101

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“…Yet another population of VTA dopamine neurons, the mPFC projectors, are involved in aversive valence processing (Lammel et al, 2011;Vander Weele et al, 2018), and a dopamine projection from the VTA to the NAc and to the CeA is involved in fear memory and fear discrimination (Jo et al, 2018). Thus, together with the VTA dopamine neurons projecting to the BA that we have studied here, there are different populations of VTA dopamine projection neurons involved in aversive learning.…”

Section: Discussionmentioning

confidence: 92%

“…3 suggest that dopamine neurons in the VTA contribute to the formation of auditory -cued threat memories. Nevertheless, there are several possible output projections of VTA dopamine neurons that might contribute to aversive learning, including projections to the mPFC and NAc (Vander Weele et al, 2018;de Jong et al, 2019), as well as the projection to the BA that we characterized anatomically (Fig. 1).…”

Section: The Vta To Ba Projection Contributes To Auditory Cued Threatmentioning

confidence: 99%

Dopamine in the basal amygdala signals salient somatosensory events during fear learning

Tang

Kochubey

Kintscher

et al. 2019

Preprint

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2 SummaryThe amygdala is a brain area critical for the formation of threat 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 whether dopamine release in the amygdala contributes to fear learning. Antero-and retrograde labeling showed that a sparse, and relatively evenly distributed population of ventral tegmental area (VTA) neurons projects to the basal amygdala (BA). In-vivo optrode recordings in behaving mice showed that many VTA neurons, amongst them putative dopamine neurons, are excited by footshocks. Correspondingly, in-vivo fiber photometry of dopamine in the BA revealed robust dopamine concentration transients upon footshock presentation. Finally, silencing VTA dopamine neurons, or their axon terminals in the BA during the footshock, reduced the extent of threat memory retrieval one day later. Thus, VTA dopamine neurons projecting to the BA code for the saliency of the footshock event, and the resulting dopamine release in the BA facilitates threat memory formation.

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“…In particular, the mPFC is linked to behavioral flexibility in humans and other animals 43,44 . The dopamine release in mPFC modulates its activity and plasticity 45 , which is altered in animal models of stress 8,28 . To directly evaluate DA signaling in mPFC, we transduced neonatal mice with AAV1.CAG.Flex.GCaMP6f in the VTA, followed by unilateral fiber implants in the mPFC, and trained them in the sLH paradigm (Extended Data Figure 3a, b).…”

Section: Aversive Experience and Ketamine Regulate Mpfc Da Activity Amentioning

confidence: 99%

Ketamine restores escape behavior by re-engaging dopamine systems to drive cortical spinogenesis

Minkowicz

Dumrongprechachan

et al. 2020

Preprint

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Escaping aversive stimuli is essential for complex organisms, but prolonged exposure to stress leads to maladaptive learning. Stress alters neuronal activity in distributed networks, plasticity, and neuromodulatory signaling; yet, the field lacks a unifying framework for its variegated sequelae. Here we build this framework using learned helplessness paradigm, where ketamine restores escape behavior after aversive learning. Lowdimensional optical readout of dopamine (DA) neuron activity across learning predicts acute behavioral responses, transitions through learning phases, and future sensitivity to ketamine treatment. Ketamine's effects are blocked by chemogenetic inhibition of DA signaling and mimicked by optogenetic activation. We use 2-photon glutamate uncaging/imaging to interrogate structural plasticity in medial prefrontal cortex, revealing that dendritic spinogenesis on pyramidal neurons is regulated by aversive experience and recovered by ketamine in a DA-dependent manner. Together, these data describe recurrent circuits that causally link neuromodulatory dynamics, aversive learning, and plasticity enhancements driven by a therapeutically promising anti-depressant. 3 Ketamine and its S-enantiomer esketamine, which act as antagonists of the glutamatergic N-methyl-Daspartate (NMDA) receptors, demonstrate rapid onset anti-depressant effects in clinical trials 1,2 . Previous studies have shown that ketamine ameliorates depressive-like behaviors in animal models following acute or prolonged stress [3][4][5][6][7] . Accumulating evidence implicates the enhancement of synaptic plasticity in ketamine's behavioral effects 5,6,[8][9][10][11][12] . However, which neural circuit dynamics mediate the effects of this rapidly acting antidepressant on behavior and plasticity are currently unknown.Changes in reward-based and aversive learning represent features of depressive disorders that can be modeled in rodents [13][14][15] . One established model of aversive learning is learned helplessness [16][17][18] . Following prolonged inescapable stress exposure, animals learn that outcomes are independent of their behavioral actions; this learning eventually diminishes attempts to escape from avoidable stressful stimuli 19 . Specific activity patterns of dopaminergic (DA) neurons in the ventral tegmental area (VTA), and downstream DA release, encode reward and aversion [20][21][22][23][24] . This activity is differentially modulated by acute and chronic stress [25][26][27] , regulating depressive-like behaviors [28][29][30] . A recently published meta-analysis suggests that acute sub-anesthetic doses of ketamine may increase DA levels in the cortex, dorsal striatum, and nucleus accumbens 31,32 , but the causal relationship between the DA system and ketamine's effects on neural plasticity and behavior remains to be elucidated. Low dimensional readout of DA neuron activity dynamics in aversive learningTo define the function of midbrain DA neurons during aversive learning, we used a modified model of learned helplessness 5,32 ...

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Dopamine enhances signal-to-noise ratio in cortical-brainstem encoding of aversive stimuli

Cited by 241 publications

References 55 publications

Neural mechanisms of social homeostasis

Neural mechanisms of social homeostasis

Dopamine in the basal amygdala signals salient somatosensory events during fear learning

Ketamine restores escape behavior by re-engaging dopamine systems to drive cortical spinogenesis

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