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Melissa J Sharpe
Hot off the Press!

Dopamine transients are sufficient and necessary for acquisition of model-based associations.

Nat Neurosci. 2017 Apr 3. doi: 10.1038/nn.4538. [Epub ahead of print]

Melissa J Sharpe, Chun Yun Chang, Melissa A Liu, Hannah M Batchelor, Lauren E Mueller, Joshua L Jones, Yael Niv & Geoffrey Schoenbaum

Associative learning is driven by prediction errors. Dopamine transients correlate with these errors, which current interpretations limit to endowing cues with a scalar quantity reflecting the value of future rewards. We tested whether dopamine might act more broadly to support learning of an associative model of the environment. Using sensory preconditioning, we show that prediction errors underlying stimulus-stimulus learning can be blocked behaviorally and reinstated by optogenetically activating dopamine neurons. We further show that suppressing the firing of these neurons across the transition prevents normal stimulus-stimulus learning...

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Daniele Caprioli
Daniele Caprioli
Featured paper of the Month!

Role of Dorsomedial Striatum Neuronal Ensembles in Incubation of Methamphetamine Craving after Voluntary Abstinence

J Neurosci. 2017 Jan 25;37(4):1014-1027. doi: 10.1523/JNEUROSCI.3091-16.2017.

Daniele Caprioli, Marco Venniro, Michelle Zhang, Jennifer M. Bossert, Brandon L. Warren, Bruce T. Hope, and Yavin Shaham

We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to selfadminister palatable food pellets (6 d, 6 h/d) and methamphetamine (12 d, 6 h/d). We then assessed relapse to methamphetamine...

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A figure from this month's paper.
A figure from this month's paper.
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Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior

Nat Neurosci. 2017 Mar;20(3):438-448. doi: 10.1038/nn.4482. Epub 2017 Jan 23.

Edwards NJ, Tejeda HA, Pignatelli M, Zhang S, McDevitt RA, Wu J, Bass CE, Bettler B, Morales M, Bonci A.

Afferent inputs to the ventral tegmental area (VTA) control reward-related behaviors through regulation of dopamine neuron activity. The nucleus accumbens (NAc) provides one of the most prominent projections to the VTA; however, recent studies have provided conflicting evidence regarding the function of these inhibitory inputs. Using optogenetics, cell-specific ablation, whole cell patch-clamp and immuno-electron microscopy, we found that NAc inputs synapsed directly onto dopamine neurons, preferentially activating GABAB receptors. GABAergic inputs from the NAc and local VTA GABA neurons were differentially...

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Sufang Li

Sufang Li
Featured paper of the Month!

FEBRUARY: CYP2A6 Genetic Variation Alters Striatal-Cingulate Circuits, Network Hubs, and Executive Processing in Smokers.

Biol Psychiatry. 2016 Sep 28. pii: S0006-3223(16)32824-4. 2016.09.013. [Epub ahead of print]

Li S, Yang Y, Hoffmann E, Tyndale RF, Stein EA.

METHODS: Intrinsic functional connectivity strength, a whole-brain, data-driven, graph theory-based method, was applied to resting-state functional magnetic resonance imaging data in 66 smokers and 92 nonsmokers. A subset of subjects (n = 23/20; smokers/nonsmokers) performed the monetary incentive delay task, probing reward anticipation, and a go/no-go task, probing response inhibition, on two occasions, in the presence and absence of a nicotine patch.....

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Tsung-Ping Su
Dr. Tsung-Ping Su
Reviews to Read

The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems

Trends Pharmacol Sci. 2016 Apr;37(4):262-78.

Su TP, Su TC, Nakamura Y, Tsai SY.

The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum (ER) protein that resides specifically in the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), an interface between ER and mitochondria. In addition to being able to translocate to the plasma membrane (PM) to interact with ion channels and other receptors, Sig-1R also occurs at the nuclear envelope, where it recruits chromatin-remodeling factors to affect the transcription of genes....

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Synaptic Plasticity onto Dopamine Neurons Shapes Fear Learning.

Neuron. 2017 Jan 18;93(2):425-440.

Pignatelli M, Umanah GK, Ribeiro SP, Chen R, Karuppagounder SS, Yau HJ, Eacker S, Dawson VL, Dawson TM, Bonci A.

Fear learning is a fundamental behavioral process that requires dopamine (DA) release. Experience-dependent synaptic plasticity occurs on DA neurons while an organism is engaged in aversive experiences. However, whether synaptic plasticity onto DA neurons is causally involved in aversion learning is unknown. Here, we show that a stress priming procedure enhances fear learning by engaging VTA synaptic plasticity. Moreover, we took advantage of the ability of the ATPase Thorase to regulate...

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A figure from this month's paper.
Featured paper of the Month!

JANUARY: Pontomesencephalic Tegmental Afferents to VTA Non-dopamine Neurons Are Necessary for Appetitive Pavlovian Learning

Cell Rep.2016 Sep 6;16(10):2699-710. Epub 2016 Aug 25.

Yau HJ, Wang DV, Tsou JH, Chuang YF, Chen BT, Deisseroth K, Ikemoto S, Bonci A.

The ventral tegmental area (VTA) receives phenotypically distinct innervations from the pedunculopontine tegmental nucleus (PPTg). While PPTg-to-VTA inputs are thought to play a critical role in stimulus-reward learning, direct evidence linking PPTg-to-VTA phenotypically distinct inputs in the learning process remains lacking. Here, we used optogenetic approaches to investigate the functional contribution of PPTg excitatory and inhibitory inputs to the VTA in appetitive Pavlovian conditioning....

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A figure from this month's paper.
Hot off the Press!

Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity.

Neuron. 2017 Jan 4;93(1):147-163.

Tejeda HA, Wu J, Kornspun AR, Pignatelli M, Kashtelyan V, Krashes MJ, Lowell BB, Carlezon WA Jr, Bonci A

Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic ....

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Da-Ting Lin
The Study Authors
Hot off the Press!

Spatially Compact Neural Clusters in the Dorsal Striatum Encode Locomotion Relevant Information

Neuron. 2016 Oct 5;92(1):202-213. Epub 2016 Sep 22.

Barbera G, Liang B, Zhang L, Gerfen CR, Culurciello E, Chen R, Li Y, Lin DT.

An influential striatal model postulates that neural activities in the striatal direct and indirect pathways promote and inhibit movement, respectively. Normal behavior requires coordinated activity in the direct pathway to facilitate intended locomotion and indirect pathway to inhibit unwanted locomotion. In this striatal model, neuronal population activity is assumed to encode locomotion relevant information. Here, we propose a novel encoding mechanism for the dorsal striatum. We identified spatially compact neural clusters in both the direct and indirect pathways. Detailed characterization revealed similar cluster organization between the direct and indirect pathways, and cluster activities from both pathways were correlated with mouse locomotion velocities....

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