Dopamine neurons modulate neural encoding and expression of depression-related behaviour

By K. Tye, J. J. Mirzabekov, Melissa R. Warden, Emily Ferenczi, Hsing-Chen Tsai, Joel Finkelstein, Sung-Yon Kim, Avishek Adhikari, K. Thompson, A. Andalman and 3 more. Nature, 2012

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Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia. Dopamine neurons involved in reward and motivation are among many neural populations that have been hypothesized to be relevant, and certain antidepressant treatments, including medications and brain stimulation therapies, can influence the complex dopamine system. Until now it has not been possible to test this hypothesis directly, even in animal models, as existing therapeutic interventions are unable to specifically target dopamine neurons. Here we investigated directly the causal contributions of defined dopamine neurons to multidimensional depression-like phenotypes induced by chronic mild stress, by integrating behavioural, pharmacological, optogenetic and electrophysiological methods in freely moving rodents. We found that bidirectional control (inhibition or excitation) of specified midbrain dopamine neurons immediately and bidirectionally modulates (induces or relieves) multiple independent depression symptoms caused by chronic stress. By probing the circuit implementation of these effects, we observed that optogenetic recruitment of these dopamine neurons potently alters the neural encoding of depression-related behaviours in the downstream nucleus accumbens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/601289d68f500b39a268d9577f1ee6c1a3ddaa9b

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Citations in the corpus

Insulin Action in Brain Regulates Systemic Metabolism and Brain Function (2014, background): “Insulin signaling has been shown to modulate the dopaminergic and serotonergic systems, which are pathways that play a pivotal role in depression (104,105).”
Natural neural projection dynamics underlying social behavior. (2014, neutral): “…Deisseroth1,3,4,* 1Department of Bioengineering 2Neuroscience Program 3Department of Psychiatry and Behavioral Sciences 4Howard Hughes Medical Institute Stanford University, Stanford, CA 94305, USA 5Co-first author *Correspondence: deissero@stanford.edu http://dx.doi.org/10.1016/j.cell.2014.05.017”
Reward and aversion in a heterogeneous midbrain dopamine system (2013, background): “…(Aragona et al., 2009; Beckley et al., 2013; Brischoux et al., 2009; Chaudhury et al., 2012; Lammel et al., 2011, 2012; Schieman et al., 2012; Tye et al., 2012) provide further evidence supporting the importance of a heterogeneous midbrain DA system in mediating the pathophysiology of…”
Dopamine System Dysregulation in Major Depressive Disorders (2017, background): “Only DA neurons that fire spontaneously can fire in response to rapid, phasic activation with bursts of action potentials, due to activation of pedunculopontine tegmental nucleus (PPTg) afferents. exposed to CMS show elevated hypothalamo-pituitary-adrenal axis activity (Goshen et al., 2008), decreas”
The chronic mild stress (CMS) model of depression: History, evaluation and usage (2016, background): “Of particular interest, activation of the amygdala by CMS causes a decrease in the activity of mesolimbic dopamine cells in the ventral tegmental area (VTA) (Chang and Grace, 2014).”