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Henry Yin

Professor of Psychology and Neuroscience
Psychology & Neuroscience
GSRB II, Box 91050, Durham, NC 27708-0086
GSRB II Rm 3012, Box 91050, Durham, NC 27708

Selected Publications


The integrative functions of the basal ganglia

Book · November 6, 2023 This volume is the first comprehensive and single-authored book on the functions of the basal ganglia. The goal is to provide a new synthesis of diverse areas of research on the basal ganglia, from cellular mechanisms of synaptic transmission and plasticit ... Full text Cite

Selective Activation of Subthalamic Nucleus Output Quantitatively Scales Movements.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · November 2023 The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) treatments of Parkinsonian motor symptoms. According to the dominant model, the STN output can suppress movement by enhancing inhibitory basal ganglia (BG) output via the ind ... Full text Cite

Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control.

Journal Article Nat Commun · September 8, 2023 Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant conditioning via lever-press for food reward training ... Full text Link to item Cite

The role of the parafascicular thalamic nucleus in action initiation and steering.

Journal Article Current biology : CB · July 2023 The parafascicular (Pf) nucleus of the thalamus has been implicated in arousal and attention, but its contributions to behavior remain poorly characterized. Here, using in vivo and in vitro electrophysiology, optogenetics, and 3D motion capture, we studied ... Full text Cite

Cortical regulation of neurogenesis and cell proliferation in the ventral subventricular zone.

Journal Article Cell reports · July 2023 Neurogenesis and differentiation of neural stem cells (NSCs) are controlled by cell-intrinsic molecular pathways that interact with extrinsic signaling cues. In this study, we identify a circuit that regulates neurogenesis and cell proliferation in the lat ... Full text Cite

A one-photon endoscope for simultaneous patterned optogenetic stimulation and calcium imaging in freely behaving mice.

Journal Article Nature biomedical engineering · April 2023 Optogenetics and calcium imaging can be combined to simultaneously stimulate and record neural activity in vivo. However, this usually requires two-photon microscopes, which are not portable nor affordable. Here we report the design and implementation of a ... Full text Cite

Elucidating a locus coeruleus-dentate gyrus dopamine pathway for operant reinforcement.

Journal Article eLife · April 2023 Animals can learn to repeat behaviors to earn desired rewards, a process commonly known as reinforcement learning. While previous work has implicated the ascending dopaminergic projections to the basal ganglia in reinforcement learning, little is known abo ... Full text Cite

Striatal mechanisms of turning behaviour following unilateral dopamine depletion in mice.

Journal Article The European journal of neuroscience · September 2022 Unilateral dopamine (DA) depletion produces ipsiversive turning behaviour, and the injection of DA receptor agonists can produce contraversive turning, but the underlying mechanisms remain unclear. We conducted in vivo recording and pharmacological and opt ... Full text Cite

Neural circuit pathology driven by Shank3 mutation disrupts social behaviors.

Journal Article Cell reports · June 2022 Dysfunctional sociability is a core symptom in autism spectrum disorder (ASD) that may arise from neural-network dysconnectivity between multiple brain regions. However, pathogenic neural-network mechanisms underlying social dysfunction are largely unknown ... Full text Cite

Closing the loop on models of interval timing.

Journal Article Nature neuroscience · March 2022 Full text Cite

Achieving natural behavior in a robot using neurally inspired hierarchical perceptual control

Journal Article iScience · September 24, 2021 Terrestrial locomotion presents tremendous computational challenges on account of the enormous degrees of freedom in legged animals, and complex, unpredictable properties of natural environments, including the body and its effectors, yet the nervous system ... Full text Cite

Hypothalamic-Extended Amygdala Circuit Regulates Temporal Discounting.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · March 2021 Choice behavior is characterized by temporal discounting, i.e., preference for immediate rewards given a choice between immediate and delayed rewards. Agouti-related peptide (AgRP)-expressing neurons located in the arcuate nucleus of the hypothalamus (ARC) ... Full text Cite

Thalamic projections to the subthalamic nucleus contribute to movement initiation and rescue of parkinsonian symptoms.

Journal Article Science advances · February 2021 The parafascicular nucleus (Pf) of the thalamus provides major projections to the basal ganglia, a set of subcortical nuclei involved in action initiation. Here, we show that Pf projections to the subthalamic nucleus (STN), but not to the striatum, are res ... Full text Cite

Protocol for Recording from Ventral Tegmental Area Dopamine Neurons in Mice while Measuring Force during Head-Fixation.

Journal Article STAR protocols · September 2020 Many studies in systems neuroscience use head-fixation preparations for in vivo experimentation. While head-fixation confers several advantages, one major limitation is the lack of behavioral measures that quantify whole-body movements. Here, we det ... Full text Cite

Mediodorsal Thalamus Contributes to the Timing of Instrumental Actions.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · August 2020 The perception of time is critical to adaptive behavior. While prefrontal cortex and basal ganglia have been implicated in interval timing in the seconds to minutes range, little is known about the role of the mediodorsal thalamus (MD), which is a key comp ... Full text Cite

Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction.

Journal Article Cell Rep · July 28, 2020 Psychiatric disorders are highly heritable pathologies of altered neural circuit functioning. How genetic mutations lead to specific neural circuit abnormalities underlying behavioral disruptions, however, remains unclear. Using circuit-selective transgeni ... Full text Link to item Cite

Ventral Tegmental Dopamine Neurons Control the Impulse Vector during Motivated Behavior.

Journal Article Current biology : CB · July 2020 The ventral tegmental area (VTA) is a major source of dopamine, especially to the limbic brain regions. Despite decades of research, the function of VTA dopamine neurons remains controversial. Here, using a novel head-fixed behavioral system with five orth ... Full text Cite

Opponent regulation of action performance and timing by striatonigral and striatopallidal pathways.

Journal Article eLife · April 2020 The basal ganglia have been implicated in action selection and timing, but the relative contributions of the striatonigral (direct) and striatopallidal (indirect) pathways to these functions remain unclear. We investigated the effects of optogenetic stimul ... Full text Cite

Striatal Projection Neurons Require Huntingtin for Synaptic Connectivity and Survival.

Journal Article Cell Rep · January 21, 2020 Huntington's disease (HD) is caused by an autosomal dominant polyglutamine expansion mutation of Huntingtin (HTT). HD patients suffer from progressive motor, cognitive, and psychiatric impairments, along with significant degeneration of the striatal projec ... Full text Link to item Cite

The integrative functions of the basal ganglia

Book · November 6, 2023 This volume is the first comprehensive and single-authored book on the functions of the basal ganglia. The goal is to provide a new synthesis of diverse areas of research on the basal ganglia, from cellular mechanisms of synaptic transmission and plasticit ... Full text Cite

Selective Activation of Subthalamic Nucleus Output Quantitatively Scales Movements.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · November 2023 The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) treatments of Parkinsonian motor symptoms. According to the dominant model, the STN output can suppress movement by enhancing inhibitory basal ganglia (BG) output via the ind ... Full text Cite

Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control.

Journal Article Nat Commun · September 8, 2023 Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant conditioning via lever-press for food reward training ... Full text Link to item Cite

The role of the parafascicular thalamic nucleus in action initiation and steering.

Journal Article Current biology : CB · July 2023 The parafascicular (Pf) nucleus of the thalamus has been implicated in arousal and attention, but its contributions to behavior remain poorly characterized. Here, using in vivo and in vitro electrophysiology, optogenetics, and 3D motion capture, we studied ... Full text Cite

Cortical regulation of neurogenesis and cell proliferation in the ventral subventricular zone.

Journal Article Cell reports · July 2023 Neurogenesis and differentiation of neural stem cells (NSCs) are controlled by cell-intrinsic molecular pathways that interact with extrinsic signaling cues. In this study, we identify a circuit that regulates neurogenesis and cell proliferation in the lat ... Full text Cite

A one-photon endoscope for simultaneous patterned optogenetic stimulation and calcium imaging in freely behaving mice.

Journal Article Nature biomedical engineering · April 2023 Optogenetics and calcium imaging can be combined to simultaneously stimulate and record neural activity in vivo. However, this usually requires two-photon microscopes, which are not portable nor affordable. Here we report the design and implementation of a ... Full text Cite

Elucidating a locus coeruleus-dentate gyrus dopamine pathway for operant reinforcement.

Journal Article eLife · April 2023 Animals can learn to repeat behaviors to earn desired rewards, a process commonly known as reinforcement learning. While previous work has implicated the ascending dopaminergic projections to the basal ganglia in reinforcement learning, little is known abo ... Full text Cite

Striatal mechanisms of turning behaviour following unilateral dopamine depletion in mice.

Journal Article The European journal of neuroscience · September 2022 Unilateral dopamine (DA) depletion produces ipsiversive turning behaviour, and the injection of DA receptor agonists can produce contraversive turning, but the underlying mechanisms remain unclear. We conducted in vivo recording and pharmacological and opt ... Full text Cite

Neural circuit pathology driven by Shank3 mutation disrupts social behaviors.

Journal Article Cell reports · June 2022 Dysfunctional sociability is a core symptom in autism spectrum disorder (ASD) that may arise from neural-network dysconnectivity between multiple brain regions. However, pathogenic neural-network mechanisms underlying social dysfunction are largely unknown ... Full text Cite

Closing the loop on models of interval timing.

Journal Article Nature neuroscience · March 2022 Full text Cite

Achieving natural behavior in a robot using neurally inspired hierarchical perceptual control

Journal Article iScience · September 24, 2021 Terrestrial locomotion presents tremendous computational challenges on account of the enormous degrees of freedom in legged animals, and complex, unpredictable properties of natural environments, including the body and its effectors, yet the nervous system ... Full text Cite

Hypothalamic-Extended Amygdala Circuit Regulates Temporal Discounting.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · March 2021 Choice behavior is characterized by temporal discounting, i.e., preference for immediate rewards given a choice between immediate and delayed rewards. Agouti-related peptide (AgRP)-expressing neurons located in the arcuate nucleus of the hypothalamus (ARC) ... Full text Cite

Thalamic projections to the subthalamic nucleus contribute to movement initiation and rescue of parkinsonian symptoms.

Journal Article Science advances · February 2021 The parafascicular nucleus (Pf) of the thalamus provides major projections to the basal ganglia, a set of subcortical nuclei involved in action initiation. Here, we show that Pf projections to the subthalamic nucleus (STN), but not to the striatum, are res ... Full text Cite

Protocol for Recording from Ventral Tegmental Area Dopamine Neurons in Mice while Measuring Force during Head-Fixation.

Journal Article STAR protocols · September 2020 Many studies in systems neuroscience use head-fixation preparations for in vivo experimentation. While head-fixation confers several advantages, one major limitation is the lack of behavioral measures that quantify whole-body movements. Here, we det ... Full text Cite

Mediodorsal Thalamus Contributes to the Timing of Instrumental Actions.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · August 2020 The perception of time is critical to adaptive behavior. While prefrontal cortex and basal ganglia have been implicated in interval timing in the seconds to minutes range, little is known about the role of the mediodorsal thalamus (MD), which is a key comp ... Full text Cite

Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction.

Journal Article Cell Rep · July 28, 2020 Psychiatric disorders are highly heritable pathologies of altered neural circuit functioning. How genetic mutations lead to specific neural circuit abnormalities underlying behavioral disruptions, however, remains unclear. Using circuit-selective transgeni ... Full text Link to item Cite

Ventral Tegmental Dopamine Neurons Control the Impulse Vector during Motivated Behavior.

Journal Article Current biology : CB · July 2020 The ventral tegmental area (VTA) is a major source of dopamine, especially to the limbic brain regions. Despite decades of research, the function of VTA dopamine neurons remains controversial. Here, using a novel head-fixed behavioral system with five orth ... Full text Cite

Opponent regulation of action performance and timing by striatonigral and striatopallidal pathways.

Journal Article eLife · April 2020 The basal ganglia have been implicated in action selection and timing, but the relative contributions of the striatonigral (direct) and striatopallidal (indirect) pathways to these functions remain unclear. We investigated the effects of optogenetic stimul ... Full text Cite

Striatal Projection Neurons Require Huntingtin for Synaptic Connectivity and Survival.

Journal Article Cell Rep · January 21, 2020 Huntington's disease (HD) is caused by an autosomal dominant polyglutamine expansion mutation of Huntingtin (HTT). HD patients suffer from progressive motor, cognitive, and psychiatric impairments, along with significant degeneration of the striatal projec ... Full text Link to item Cite

A Head-Fixation System for Continuous Monitoring of Force Generated During Behavior.

Journal Article Frontiers in integrative neuroscience · January 2020 Many studies in neuroscience use head-fixed behavioral preparations, which confer a number of advantages, including the ability to limit the behavioral repertoire and use techniques for large-scale monitoring of neural activity. But traditional studies usi ... Full text Cite

The crisis in neuroscience

Chapter · January 1, 2020 The dominant paradigm in neuroscience, the linear causation paradigm, has led to a number of conceptual confusions about how the brain generates behavior. Because biological organisms are collections of closed loop control systems, their behaviors cannot b ... Full text Cite

Precise Coordination of Three-Dimensional Rotational Kinematics by Ventral Tegmental Area GABAergic Neurons.

Journal Article Current biology : CB · October 2019 The ventral tegmental area (VTA) is a midbrain region implicated in a variety of motivated behaviors. However, the function of VTA GABAergic (Vgat+) neurons remains poorly understood. Here, using three-dimensional motion capture, in vivo electrophysiology, ... Full text Cite

ANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity.

Journal Article Proc Natl Acad Sci U S A · July 23, 2019 Giant ankyrin-B (ankB) is a neurospecific alternatively spliced variant of ANK2, a high-confidence autism spectrum disorder (ASD) gene. We report that a mouse model for human ASD mutation of giant ankB exhibits increased axonal branching in cultured neuron ... Full text Link to item Cite

A striatal interneuron circuit for continuous target pursuit.

Journal Article Nat Commun · June 20, 2019 Most adaptive behaviors require precise tracking of targets in space. In pursuit behavior with a moving target, mice use distance to target to guide their own movement continuously. Here, we show that in the sensorimotor striatum, parvalbumin-positive fast ... Full text Link to item Cite

Thrombospondin receptor α2δ-1 promotes synaptogenesis and spinogenesis via postsynaptic Rac1.

Journal Article J Cell Biol · October 1, 2018 Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus the TSP-α2δ-1 interaction is imp ... Full text Link to item Cite

Postnatal TrkB ablation in corticolimbic interneurons induces social dominance in male mice.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · October 2018 The tight balance between synaptic excitation and inhibition (E/I) within neocortical circuits in the mammalian brain is important for complex behavior. Many loss-of-function studies have demonstrated that brain-derived neurotrophic factor (BDNF) and its c ... Full text Cite

Publisher Correction: A craniofacial-specific monosynaptic circuit enables heightened affective pain.

Journal Article Nat Neurosci · June 2018 In the version of this article initially published, ORCID links were missing for authors Erica Rodriguez, Koji Toda and Fan Wang. The error has been corrected in the HTML and PDF versions of the article. ... Full text Link to item Cite

Brain region-specific disruption of Shank3 in mice reveals a dissociation for cortical and striatal circuits in autism-related behaviors.

Journal Article Transl Psychiatry · April 27, 2018 We previously reported a new line of Shank3 mutant mice which led to a complete loss of Shank3 by deleting exons 4-22 (Δe4-22) globally. Δe4-22 mice display robust ASD-like behaviors including impaired social interaction and communication, increased stereo ... Full text Link to item Cite

Recent Insights into Corticostriatal Circuit Mechanisms underlying Habits: Invited review for Current Opinions in Behavioral Sciences.

Journal Article Curr Opin Behav Sci · April 2018 Habits have been studied for decades, but it was not until recent years that experiments began to elucidate the underlying cellular and circuit mechanisms. The latest experiments have been enabled by advances in cell-type specific monitoring and manipulati ... Full text Link to item Cite

A craniofacial-specific monosynaptic circuit enables heightened affective pain.

Journal Article Nat Neurosci · December 2017 Humans often rank craniofacial pain as more severe than body pain. Evidence suggests that a stimulus of the same intensity induces stronger pain in the face than in the body. However, the underlying neural circuitry for the differential processing of facia ... Full text Open Access Link to item Cite

Nigrotectal Stimulation Stops Interval Timing in Mice.

Journal Article Current biology : CB · December 2017 Considerable evidence implicates the basal ganglia in interval timing, yet the underlying mechanisms remain poorly understood. Using a novel behavioral task, we demonstrate that head-fixed mice can be trained to show the key features of timing behavior wit ... Full text Cite

Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers.

Journal Article JCI Insight · October 19, 2017 Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underly ... Full text Link to item Cite

Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior.

Journal Article Elife · September 5, 2017 Habit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these ci ... Full text Link to item Cite

The Basal Ganglia in Action.

Journal Article The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · June 2017 The basal ganglia (BG) are the major subcortical nuclei in the brain. Disorders implicating the BG are characterized by diverse symptoms, but it remains unclear what these symptoms have in common or how they can be explained by changes in the BG circuits. ... Full text Cite

Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism.

Journal Article Nat Commun · May 10, 2016 Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout m ... Full text Open Access Link to item Cite

A GABAergic nigrotectal pathway for coordination of drinking behavior.

Journal Article Nat Neurosci · May 2016 The contribution of basal ganglia outputs to consummatory behavior remains poorly understood. We recorded from the substantia nigra pars reticulata (SNR), the major basal ganglia output nucleus, during self-initiated drinking in mice. The firing rates of m ... Full text Link to item Cite

The role of opponent basal ganglia outputs in behavior

Journal Article Future Neurology · May 1, 2016 This review is an attempt to explain the role of basal ganglia (BG) outputs in generating movements. Recent work showed that opponent outputs from the BG represent instantaneous body position coordinates during behavior. On the other hand, projection neuro ... Full text Cite

Striatonigral control of movement velocity in mice.

Journal Article The European journal of neuroscience · April 2016 The basal ganglia have long been implicated in action initiation. Using three-dimensional motion capture, we quantified the effects of optogenetic stimulation of the striatonigral (direct) pathway on movement kinematics. We generated transgenic mice with c ... Full text Cite

Pathway-Specific Striatal Substrates for Habitual Behavior.

Journal Article Neuron · February 3, 2016 The dorsolateral striatum (DLS) is implicated in habit formation. However, the DLS circuit mechanisms underlying habit remain unclear. A key role for DLS is to transform sensorimotor cortical input into firing of output neurons that project to the mutually ... Full text Link to item Cite

Luminopsins integrate opto- and chemogenetics by using physical and biological light sources for opsin activation.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · January 2016 Luminopsins are fusion proteins of luciferase and opsin that allow interrogation of neuronal circuits at different temporal and spatial resolutions by choosing either extrinsic physical or intrinsic biological light for its activation. Building on previous ... Full text Cite

Human Umbilical Tissue-Derived Cells Promote Synapse Formation and Neurite Outgrowth via Thrombospondin Family Proteins.

Journal Article J Neurosci · November 25, 2015 UNLABELLED: Cell therapy demonstrates great potential for the treatment of neurological disorders. Human umbilical tissue-derived cells (hUTCs) were previously shown to have protective and regenerative effects in animal models of stroke and retinal degener ... Full text Link to item Cite

Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine.

Journal Article Nat Neurosci · June 2015 Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical beh ... Full text Link to item Cite

Elevated dopamine alters consummatory pattern generation and increases behavioral variability during learning

Journal Article Frontiers in Integrative Neuroscience · May 15, 2015 The role of dopamine in controlling behavior remains poorly understood. In this study we examined licking behavior in an established hyperdopaminergic mouse model—dopamine transporter knockout (DAT KO) mice. DAT KO mice showed higher rates of licking, whic ... Full text Cite

Spotlight on movement disorders: What optogenetics has to offer.

Journal Article Mov Disord · April 15, 2015 Elucidating the neuronal mechanisms underlying movement disorders is a major challenge because of the intricacy of the relevant neural circuits, which are characterized by diverse cell types and complex connectivity. A major limitation of traditional techn ... Full text Link to item Cite

Basal ganglia outputs map instantaneous position coordinates during behavior.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · February 2015 The basal ganglia (BG) are implicated in many movement disorders, yet how they contribute to movement remains unclear. Using wireless in vivo recording, we measured BG output from the substantia nigra pars reticulata (SNr) in mice while monitoring their mo ... Full text Cite

Giant ankyrin-G: a critical innovation in vertebrate evolution of fast and integrated neuronal signaling.

Journal Article Proc Natl Acad Sci U S A · January 27, 2015 Axon initial segments (AISs) and nodes of Ranvier are sites of clustering of voltage-gated sodium channels (VGSCs) in nervous systems of jawed vertebrates that facilitate fast long-distance electrical signaling. We demonstrate that proximal axonal polarity ... Full text Link to item Cite

A wirelessly controlled implantable LED system for deep brain optogenetic stimulation.

Journal Article Frontiers in integrative neuroscience · January 2015 In recent years optogenetics has rapidly become an essential technique in neuroscience. Its temporal and spatial specificity, combined with efficacy in manipulating neuronal activity, are especially useful in studying the behavior of awake behaving animals ... Full text Open Access Cite

Beyond reward prediction errors: the role of dopamine in movement kinematics.

Journal Article Frontiers in integrative neuroscience · January 2015 We recorded activity of dopamine (DA) neurons in the substantia nigra pars compacta in unrestrained mice while monitoring their movements with video tracking. Our approach allows an unbiased examination of the continuous relationship between single unit ac ... Full text Cite

Striatal firing rate reflects head movement velocity.

Journal Article The European journal of neuroscience · November 2014 Although the basal ganglia have long been implicated in the initiation of actions, their contribution to movement remains a matter of dispute. Using wireless multi-electrode recording and motion tracking, we examined the relationship between single-unit ac ... Full text Cite

Huntingtin is required for normal excitatory synapse development in cortical and striatal circuits.

Journal Article J Neurosci · July 9, 2014 Huntington's disease (HD) is a neurodegenerative disease caused by the expansion of a poly-glutamine (poly-Q) stretch in the huntingtin (Htt) protein. Gain-of-function effects of mutant Htt have been extensively investigated as the major driver of neurodeg ... Full text Open Access Link to item Cite

The role of the substantia nigra in posture control.

Journal Article The European journal of neuroscience · May 2014 Disorders implicating the basal ganglia are often characterized by postural deficits, but little is known about the role of the basal ganglia in posture control. Using wireless multi-electrode recording, we measured single unit activity from GABAergic and ... Full text Cite

The role of pedunculopontine nucleus in choice behavior under risk.

Journal Article The European journal of neuroscience · May 2014 The dopaminergic projections to the basal ganglia have long been implicated in reward-guided behavior and decision-making, yet little is known about the role of the posterior pedunculopontine nucleus (pPPN), a major source of excitatory input to the mesoli ... Full text Cite

Action, time and the basal ganglia.

Journal Article Philosophical transactions of the Royal Society of London. Series B, Biological sciences · March 2014 The ability to control the speed of movement is compromised in neurological disorders involving the basal ganglia, a set of subcortical cerebral nuclei that receive prominent dopaminergic projections from the midbrain. For example, bradykinesia, slowness o ... Full text Cite

Region-specific impairments in striatal synaptic transmission and impaired instrumental learning in a mouse model of Angelman syndrome.

Journal Article The European journal of neuroscience · March 2014 Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation and impaired speech. Because patients with this disorder often exhibit motor tremor and stereotypical behaviors, which are associated with basal ganglia pathology, ... Full text Cite

The role of pedunculopontine nucleus in choice behavior under risk

Journal Article European Journal of Neuroscience · 2014 Cite

Cortico-Basal Ganglia Networks and the Neural Substrates of Actions

Journal Article · January 1, 2014 This chapter reviews the mechanisms underlying reward-guided behavior and their implications for alcohol addiction. It can be divided into three parts. First, I review recent innovations in the analysis of goal-directed behavior using instrumental conditio ... Full text Cite

Restoring purpose in behavior

Chapter · January 1, 2013 The dominant paradigm in the study of behavior today is the linear causation paradigm. This paradigm, inspired by classical physics, assumes that causes precede effects, that the behavior of organisms is caused by antecedent events inside and outside the o ... Full text Cite

Operant self-stimulation of dopamine neurons in the substantia nigra.

Journal Article PloS one · January 2013 We examined the contribution of the nigrostriatal DA system to instrumental learning and behavior using optogenetics in awake, behaving mice. Using Cre-inducible channelrhodopsin-2 (ChR2) in mice expressing Cre recombinase driven by the tyrosine hydroxylas ... Full text Cite

Bidirectional modulation of substantia nigra activity by motivational state.

Journal Article PloS one · January 2013 A major output nucleus of the basal ganglia is the substantia nigra pars reticulata, which sends GABAergic projections to brainstem and thalamic nuclei. The GABAergic (GABA) neurons are reciprocally connected with nearby dopaminergic neurons, which project ... Full text Cite

Prefrontal cortical mechanisms underlying delayed alternation in mice.

Journal Article Journal of neurophysiology · August 2012 The prefrontal cortex (PFC) has been implicated in the maintenance of task-relevant information during goal-directed behavior. Using a combination of lesions, local inactivation, and optogenetics, we investigated the functional role of the medial prefronta ... Full text Cite

Methods for studying habitual behavior in mice

Journal Article Current protocols in neuroscience · July 2012 Cite

Mechanisms of action selection and timing in substantia nigra neurons.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · April 2012 The timing of actions is critical for adaptive behavior. In this study we measured neural activity in the substantia nigra as mice learned to change their action duration to earn food rewards. We observed dramatic changes in single unit activity during lea ... Full text Cite

Mechanisms of action selection and timing in substantia nigra neurons.

Journal Article Journal of neuroscience · 2012 Cite

Dynamic changes in single unit activity and γ oscillations in a thalamocortical circuit during rapid instrumental learning.

Journal Article PloS one · January 2012 The medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) together form a thalamocortical circuit that has been implicated in the learning and production of goal-directed actions. In this study we measured neural activity in both regions simultaneo ... Full text Cite

The role of the substantia nigra in posture control

Journal Article Journal of neuroscience · 2012 Cite

The role of the dorsal striatum in instrumental conditioning

Journal Article Neuromethods · October 24, 2011 This chapter is divided into three parts. In the first part, we introduce the theoretical foundation of instrumental conditioning and the commonly used methods to study it. In the second part, we review some recent work using these methods to investigate t ... Full text Cite

A wireless multi-channel recording system for freely behaving mice and rats.

Journal Article PloS one · January 2011 To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brai ... Full text Open Access Cite

Motivational state and reward content determine choice behavior under risk in mice.

Journal Article PloS one · January 2011 Risk is a ubiquitous feature of the environment for most organisms, who must often choose between a small and certain reward and a larger but less certain reward. To study choice behavior under risk in a genetically well characterized species, we trained m ... Full text Cite

Instrumental uncertainty as a determinant of behavior under interval schedules of reinforcement

Journal Article Frontiers in Integrative Neuroscience · December 1, 2010 Interval schedules of reinforcement are known to generate habitual behavior, the performance of which is less sensitive to revaluation of the earned reward and to alterations in the action-outcome contingency. Here we report results from experiments using ... Full text Cite

The sensorimotor striatum is necessary for serial order learning.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · November 2010 Central to the production of adaptive behavior is the ability to learn the temporal order of behavioral elements (e.g., A, B, C). Yet little is known about neural substrates of serial order in self-initiated behavioral sequences. The present study assessed ... Full text Cite

The role of mediodorsal thalamus in temporal differentiation of reward-guided actions

Journal Article Frontiers in Integrative Neuroscience · May 1, 2010 The mediodorsal thalamus (MD) is a crucial component of the neural network involved in the learning and generation of goal-directed actions. A series of experiments reported here examined the contributions of MD to the temporal differentiation of reward-gu ... Full text Cite

The role of the murine motor cortex in action duration and order

Journal Article Frontiers in Integrative Neuroscience · October 9, 2009 This study examined the contributions of the primary and secondary motor cortices (M1 and M2) to action differentiation and sequencing in mice. In Experiment 1, mice with excitotoxic lesions of M1 and M2 and sham controls learned to emit lever presses exce ... Full text Cite

The role of the murine motor cortex in action duration and order

Journal Article Frontiers in integrative neuroscience · October 2009 Cite

From actions to habits

Journal Article Alcohol Research and Health · May 20, 2009 Recent work on the role of overlapping cerebral networks in action selection and habit formation has important implications for alcohol addiction research. As reviewed below, (1) these networks, which all involve a group of deep-brain structures called the ... Cite

Dynamic reorganization of striatal circuits during the acquisition and consolidation of a skill.

Journal Article Nature neuroscience · March 2009 The learning of new skills is characterized by an initial phase of rapid improvement in performance and a phase of more gradual improvements as skills are automatized and performance asymptotes. Using in vivo striatal recordings, we observed region-specifi ... Full text Cite

Neuroadaptations leading to alcohol addiction and dependence.

Journal Article Alcohol Research and Health · 2009 Cite

Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks.

Journal Article The European journal of neuroscience · October 2008 Here we challenge the view that reward-guided learning is solely controlled by the mesoaccumbens pathway arising from dopaminergic neurons in the ventral tegmental area and projecting to the nucleus accumbens. This widely accepted view assumes that reward ... Full text Cite

The elephantine shape of addiction

Journal Article Behavioral and Brain Sciences · August 1, 2008 By summarizing, in a single piece, various current perspectives on addiction, Redish et al. have performed a useful service to the field. Their central message is that addiction comprises many vulnerabilities rather than a single vulnerability. Such a mess ... Full text Cite

From actions to habits: neuroadaptations leading to dependence.

Journal Article Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism · January 2008 Recent work on the role of overlapping cerebral networks in action selection and habit formation has important implications for alcohol addiction research. As reviewed below, (1) these networks, which all involve a group of deep-brain structures called the ... Cite

Neurotensin reduces glutamatergic transmission in the dorsolateral striatum via retrograde endocannabinoid signaling.

Journal Article Neuropharmacology · January 2008 Neurotensin is a peptide that has been suggested to mimic the actions of antipsychotics, but little is known about how it affects synaptic transmission in the striatum, the major input nucleus of the basal ganglia. In this study we measured the effects of ... Full text Cite

Endocannabinoid signaling is critical for habit formation

Journal Article Frontiers in Integrative Neuroscience · November 2, 2007 Extended training can induce a shift in behavioral control from goal-directed actions, which are governed by action-outcome contingencies and sensitive to change in the expected value of the outcome, to habits which are less dependent on action-outcome rel ... Full text Cite

Ethanol reverses the direction of long-term synaptic plasticity in the dorsomedial striatum.

Journal Article The European journal of neuroscience · June 2007 The striatum is a critical structure for the control of voluntary behaviour, and striatal synaptic plasticity has been implicated in instrumental learning. As ethanol consumption can cause impairments in cognition, learning, and action selection, it is imp ... Full text Cite

Endocannabinoid signaling is required for habit formation

Journal Article Frontiers in Integrative Neuroscience · 2007 Cite

The role of protein synthesis in striatal long-term depression.

Journal Article The Journal of neuroscience : the official journal of the Society for Neuroscience · November 2006 Long-term depression (LTD) at the corticostriatal synapse is postsynaptically induced but presynaptically expressed, the depression being a result of retrograde endocannabinoid signaling that activates presynaptic cannabinoid CB1 receptors and reduces the ... Full text Cite

Disrupted motor learning and long-term synaptic plasticity in mice lacking NMDAR1 in the striatum.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · October 2006 Much research has implicated the striatum in motor learning, but the underlying mechanisms have not been identified. Although NMDA receptor (NMDAR)-dependent long-term potentiation has been observed in the striatum, its involvement in motor learning remain ... Full text Cite

The role of the basal ganglia in habit formation.

Journal Article Nature reviews. Neuroscience · June 2006 Many organisms, especially humans, are characterized by their capacity for intentional, goal-directed actions. However, similar behaviours often proceed automatically, as habitual responses to antecedent stimuli. How are goal-directed actions transformed i ... Full text Cite

Frequency-specific and D2 receptor-mediated inhibition of glutamate release by retrograde endocannabinoid signaling.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · May 2006 The mechanisms underlying modulation of corticostriatal synaptic transmission by D2-like receptors (D2Rs) have been controversial. A recent study suggested that D2Rs inhibit glutamate release at this synapse, but only during high-frequency synaptic activat ... Full text Cite

Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons.

Journal Article Neuron · May 2006 Long-term depression (LTD) of the synapse formed between cortical pyramidal neurons and striatal medium spiny neurons is central to many theories of motor plasticity and associative learning. The induction of LTD at this synapse is thought to depend upon D ... Full text Cite

Instrumental learning in hyperdopaminergic mice.

Journal Article Neurobiology of learning and memory · May 2006 In two experiments we investigated the effects of elevated dopaminergic tone on instrumental learning and performance using dopamine transporter knockdown (DAT KD) mice. In Experiment 1, we showed that both DAT KD mice and wild-type controls were similarly ... Full text Cite

Inactivation of dorsolateral striatum enhances sensitivity to changes in the action-outcome contingency in instrumental conditioning.

Journal Article Behavioural brain research · January 2006 Actions become compulsive when they are no longer controlled by their consequences. Compulsivity can be assessed using the omission procedure in which animals are required to withhold a previously reinforced action to earn reward. The current study tested ... Full text Cite

Blockade of NMDA receptors in the dorsomedial striatum prevents action-outcome learning in instrumental conditioning.

Journal Article The European journal of neuroscience · July 2005 Although there is consensus that instrumental conditioning depends on the encoding of action-outcome associations, it is not known where this learning process is localized in the brain. Recent research suggests that the posterior dorsomedial striatum (pDMS ... Full text Cite

The role of the dorsomedial striatum in instrumental conditioning.

Journal Article The European journal of neuroscience · July 2005 Considerable evidence suggests that, in instrumental conditioning, rats learn the relationship between actions and their specific consequences or outcomes. The present study examined the role of the dorsomedial striatum (DMS) in this type of learning after ... Full text Cite

Addiction and learning in the brain

Chapter · January 1, 2005 Addiction can be viewed as a maladaptive form of learning. This chapter discusses the relevant types of learning implicated in addiction and their neural substrates. First, we describe the associative structures of various learning processes-abstract descr ... Full text Cite

Contributions of striatal subregions to place and response learning.

Journal Article Learning & memory (Cold Spring Harbor, N.Y.) · July 2004 The involvement of different subregions of the striatum in place and response learning was examined using a T-maze. Rats were given NMDA lesions of the dorsolateral striatum (DLS), anterior dorsomedial striatum (ADMS), posterior dorsomedial striatum (PDMS) ... Full text Cite

Lesions of the dorsolateral striatum abolish habits and preserve goal expectancy

Journal Article European Journal of Neuroscience · 2004 Cite

Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning.

Journal Article The European journal of neuroscience · January 2004 Habits are controlled by antecedent stimuli rather than by goal expectancy. Interval schedules of feedback have been shown to generate habits, as revealed by the insensitivity of behaviour acquired under this schedule to outcome devaluation treatments. Two ... Full text Cite

Kainic acid lesions disrupt fear-mediated memory processing.

Journal Article Neurobiology of learning and memory · May 2002 Previous research has shown that hippocampal lesions impair the expression of fear conditioning. This fear conditioning deficit may be due to memory impairment or a reduction in fear in lesioned animals. To address these possibilities, the authors examined ... Full text Cite

Reinforcer devaluation abolishes conditioned cue preference: evidence for stimulus-stimulus associations.

Journal Article Behavioral neuroscience · February 2002 In the conditioned cue preference (CCP) task, the subject is presented with a cue paired with food reward, resulting in a preference for the paired cue when allowed to choose later. To clarify the learning involved, the authors devalued the reinforcer afte ... Full text Cite

From habits to actions: Dorsolateral striatum lesions alter the content of learning

Conference ICONIP 2002 - Proceedings of the 9th International Conference on Neural Information Processing: Computational Intelligence for the E-Age · January 1, 2002 Actions are controlled by the expectation of an outcome, whereas habits are elicited by the prevailing stimuli, autonomous of the outcome. In this study, the dorsolateral striatum is shown to be necessary for the formation of a habit. Rats were trained to ... Full text Cite

Retail outlet location decision maker – franchisor or franchisee?

Journal Article Marketing Intelligence & Planning · June 1, 2001 This study focuses on a unique retail outlet location decision-making problem found in business format franchising industries. The problem is derived from the latent conflict in the relationship between franchisor and franchisees. An empirical study was ca ... Full text Cite