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  1. Article ; Online: Using rodent data to elucidate dopaminergic mechanisms of ADHD: Implications for human personality.

    Tripp, Gail / Wickens, Jeff

    Personality neuroscience

    2024  Volume 7, Page(s) e2

    Abstract: An altered behavioral response to positive reinforcement has been proposed to be a core deficit in attention deficit hyperactivity disorder (ADHD). The spontaneously hypertensive rat (SHR), a congenic animal strain, displays a similarly altered response ... ...

    Abstract An altered behavioral response to positive reinforcement has been proposed to be a core deficit in attention deficit hyperactivity disorder (ADHD). The spontaneously hypertensive rat (SHR), a congenic animal strain, displays a similarly altered response to reinforcement. The presence of this genetically determined phenotype in a rodent model allows experimental investigation of underlying neural mechanisms. Behaviorally, the SHR displays increased preference for immediate reinforcement, increased sensitivity to individual instances of reinforcement relative to integrated reinforcement history, and a steeper delay of reinforcement gradient compared to other rat strains. The SHR also shows less development of incentive to approach sensory stimuli, or cues, that predict reward after repeated cue-reward pairing. We consider the underlying neural mechanisms for these characteristics. It is well known that midbrain dopamine neurons are initially activated by unexpected reward and gradually transfer their responses to reward-predicting cues. This finding has inspired the dopamine transfer deficit (DTD) hypothesis, which predicts certain behavioral effects that would arise from a deficient transfer of dopamine responses from actual rewards to reward-predicting cues. We argue that the DTD predicts the altered responses to reinforcement seen in the SHR and individuals with ADHD. These altered responses to reinforcement in turn predict core symptoms of ADHD. We also suggest that variations in the degree of dopamine transfer may underlie variations in personality dimensions related to altered reinforcement sensitivity. In doing so, we highlight the value of rodent models to the study of human personality.
    Language English
    Publishing date 2024-01-31
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2513-9886
    ISSN (online) 2513-9886
    DOI 10.1017/pen.2023.12
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Ramping activity in the striatum.

    Ponzi, Adam / Wickens, Jeff

    Frontiers in computational neuroscience

    2022  Volume 16, Page(s) 902741

    Abstract: Control of the timing of behavior is thought to require the basal ganglia (BG) and BG pathologies impair performance in timing tasks. Temporal interval discrimination depends on the ramping activity of medium spiny neurons (MSN) in the main BG input ... ...

    Abstract Control of the timing of behavior is thought to require the basal ganglia (BG) and BG pathologies impair performance in timing tasks. Temporal interval discrimination depends on the ramping activity of medium spiny neurons (MSN) in the main BG input structure, the striatum, but the underlying mechanisms driving this activity are unclear. Here, we combine an MSN dynamical network model with an action selection system applied to an interval discrimination task. We find that when network parameters are appropriate for the striatum so that slowly fluctuating marginally stable dynamics are intrinsically generated, up and down ramping populations naturally emerge which enable significantly above chance task performance. We show that emergent population activity is in very good agreement with empirical studies and discuss how MSN network dysfunction in disease may alter temporal perception.
    Language English
    Publishing date 2022-08-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452964-3
    ISSN 1662-5188
    ISSN 1662-5188
    DOI 10.3389/fncom.2022.902741
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book: A theory of the striatum

    Wickens, Jeff

    (Pergamon studies in neuroscience ; 7)

    1993  

    Author's details J. Wickens
    Series title Pergamon studies in neuroscience ; 7
    Collection
    Keywords Corpus Striatum / anatomy & histology ; Corpus Striatum / physiology ; Models, Neurological ; Computer Simulation ; Corpus striatum
    Subject Striatum ; Streifenkörper ; Streifenhügel
    Language English
    Size XI, 182 S. : Ill., graph. Darst.
    Publisher Pergamon Press
    Publishing place Oxford u.a.
    Publishing country Great Britain
    Document type Book
    HBZ-ID HT006181762
    ISBN 0-08-042278-0 ; 978-0-08-042278-7
    Database Catalogue ZB MED Medicine, Health

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  4. Article: Designing AAV Vectors for Monitoring the Subtle Calcium Fluctuations of Inferior Olive Network

    Dorgans, Kevin / Guo, Da / Kurima, Kiyoto / Wickens, Jeff / Uusisaari, Marylka Yoe

    Frontiers in cellular neuroscience

    2022  Volume 16, Page(s) 825056

    Abstract: Adeno-associated viral (AAV) vectors, used as vehicles for gene transfer into the brain, are a versatile and powerful tool of modern neuroscience that allow identifying specific neuronal populations, monitoring and modulating their activity. For ... ...

    Abstract Adeno-associated viral (AAV) vectors, used as vehicles for gene transfer into the brain, are a versatile and powerful tool of modern neuroscience that allow identifying specific neuronal populations, monitoring and modulating their activity. For consistent and reproducible results, the AAV vectors must be engineered so that they reliably and accurately target cell populations. Furthermore, transgene expression must be adjusted to sufficient and safe levels compatible with the physiology of studied cells. We undertook the effort to identify and validate an AAV vector that could be utilized for researching the inferior olivary (IO) nucleus, a structure gating critical timing-related signals to the cerebellum. By means of systematic construct generation and quantitative expression profiling, we succeeded in creating a viral tool for specific and strong transfection of the IO neurons without adverse effects on their physiology. The potential of these tools is demonstrated by expressing the calcium sensor GCaMP6s in adult mouse IO neurons. We could monitor subtle calcium fluctuations underlying two signatures of intrinsic IO activity: the subthreshold oscillations (STOs) and the variable-duration action potential waveforms both
    Language English
    Publishing date 2022-04-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2022.825056
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Kinematic analysis of bimanual movements during food handling by head-fixed rats.

    Igarashi, Masakazu / Wickens, Jeff

    Journal of neurophysiology

    2018  Volume 121, Issue 2, Page(s) 490–499

    Abstract: Bimanual coordination, in which both hands work together to achieve a goal, is crucial for the basic needs of life, such as gathering and feeding. Such coordinated motor skill is highly developed in primates, where it has been most extensively studied. ... ...

    Abstract Bimanual coordination, in which both hands work together to achieve a goal, is crucial for the basic needs of life, such as gathering and feeding. Such coordinated motor skill is highly developed in primates, where it has been most extensively studied. Rodents also exhibit remarkable dexterity and coordination of forelimbs during food handling and consumption. However, rodents have been less commonly used in the study of bimanual coordination because of limited quantitative measuring techniques. In this article we describe a high-resolution tracking system that enables kinematic analysis of rat forelimb movement. The system is used to quantify forelimb movements bilaterally in head-fixed rats during food handling and consumption. Forelimb movements occurring naturally during feeding were encoded as continuous three-dimensional trajectories. The trajectories were then automatically segmented and analyzed, using a novel algorithm, according to the laterality of movement speed or the asymmetry of movement direction across the forelimbs. Bilateral forelimb movements were frequently observed during spontaneous food handling. Both symmetry and asymmetry in movement direction were frequently observed, with symmetric bilateral movements quantitatively more common. The proposed method overcomes a limitation in the precise quantification of bimanual coordination in rodents. This enables the use of powerful rodent-based research tools such as optogenetics and chemogenetics in the further investigation of neural mechanisms of bimanual coordination. NEW & NOTEWORTHY We describe a new method for quantifying and classifying three-dimensional, bilateral forelimb trajectories in head-fixed rats. The method overcomes limits on quantifying bimanual coordination in rats. When applied to kinematic analysis of food handling behavior, continuous forelimb trajectories were automatically segmented and classified. Bilateral forelimb movements were observed more frequently than unilateral movements during spontaneous food handling. Both symmetry and asymmetry in movement direction were frequently observed. However, symmetric bilateral forelimb movements were more common.
    MeSH term(s) Animals ; Biomechanical Phenomena ; Feeding Behavior ; Forelimb/physiology ; Functional Laterality ; Head Movements ; Male ; Motor Skills ; Rats ; Rats, Long-Evans ; Restraint, Physical
    Language English
    Publishing date 2018-11-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80161-6
    ISSN 1522-1598 ; 0022-3077
    ISSN (online) 1522-1598
    ISSN 0022-3077
    DOI 10.1152/jn.00295.2018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cholinergic mechanisms in adaptive behaviour.

    Zucca, Aya / Zucca, Stefano / Wickens, Jeff

    The European journal of neuroscience

    2018  Volume 47, Issue 10, Page(s) 1146–1147

    MeSH term(s) Adaptation, Psychological/physiology ; Animals ; Cholinergic Neurons/physiology ; Corpus Striatum/physiology ; Humans ; Interneurons/physiology
    Language English
    Publishing date 2018-05-17
    Publishing country France
    Document type Editorial ; Introductory Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.13926
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Toward an anatomy of disappointment: reward-related signals from the globus pallidus.

    Wickens, Jeff

    Neuron

    2008  Volume 60, Issue 4, Page(s) 530–531

    Abstract: The globus pallidus (internal segment, GPi) is traditionally regarded as part of the motor system. In this issue of Neuron, Hong and Hikosaka report on a little known projection from the monkey GPi to the lateral habenula that is modulated by reward. ... ...

    Abstract The globus pallidus (internal segment, GPi) is traditionally regarded as part of the motor system. In this issue of Neuron, Hong and Hikosaka report on a little known projection from the monkey GPi to the lateral habenula that is modulated by reward. This adds an important branch to the brain's reward circuitry.
    MeSH term(s) Animals ; Dopamine/metabolism ; Emotions/physiology ; Globus Pallidus/anatomy & histology ; Globus Pallidus/physiology ; Habenula/anatomy & histology ; Habenula/physiology ; Humans ; Neural Pathways/anatomy & histology ; Neural Pathways/physiology ; Neurotransmitter Agents/metabolism ; Reinforcement (Psychology) ; Reward ; Ventral Tegmental Area/anatomy & histology ; Ventral Tegmental Area/physiology
    Chemical Substances Neurotransmitter Agents ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2008-11-26
    Publishing country United States
    Document type Comment ; Journal Article ; Review
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2008.11.002
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  8. Article ; Online: Reward modality modulates striatal responses to reward anticipation in ADHD: Effects of affiliative and food stimuli.

    Furukawa, Emi / Bado, Patricia / da Costa, Raquel Quimas Molina / Melo, Bruno / Erthal, Pilar / de Oliveira, Iara Peixoto / Wickens, Jeff R / Moll, Jorge / Tripp, Gail / Mattos, Paulo

    Psychiatry research. Neuroimaging

    2022  Volume 327, Page(s) 111561

    Abstract: Altered reward sensitivity has been proposed to underlie symptoms of attention deficit hyperactivity disorder (ADHD). Functional magnetic resonance imaging (fMRI) studies have reported hypoactivation to reward-predicting cues in the ventral striatum ... ...

    Abstract Altered reward sensitivity has been proposed to underlie symptoms of attention deficit hyperactivity disorder (ADHD). Functional magnetic resonance imaging (fMRI) studies have reported hypoactivation to reward-predicting cues in the ventral striatum among individuals with ADHD, using experimental designs with and without behavioral response requirements. These studies have typically used monetary incentives as rewards; however, it is unclear if these findings extend to other reward types. The current study examined striatal responses to anticipation and delivery of both affiliative and food reward images using a classical conditioning paradigm. Data from 20 typically developing young adults, and 20 individuals diagnosed with ADHD were included in a region-of-interest analysis for a priori striatal regions. Consistent with findings from studies using monetary rewards, individuals with ADHD showed decreased activation to cues predicting affiliative rewards in the bilateral ventral and dorsal striatum and increased activation to the delivery of affiliative rewards in the ventral striatum. No group differences were found in striatal responses to food reward cues or images. These results suggest hyposensitivity to reward-predicting cues in ADHD extends to affiliative rewards, with important implications for understanding and managing the learning and social functioning of those with ADHD.
    MeSH term(s) Young Adult ; Humans ; Attention Deficit Disorder with Hyperactivity/diagnostic imaging ; Reward ; Ventral Striatum/diagnostic imaging ; Magnetic Resonance Imaging ; Motivation
    Language English
    Publishing date 2022-10-25
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 445361-x
    ISSN 1872-7506 ; 1872-7123 ; 0925-4927 ; 0165-1781
    ISSN (online) 1872-7506 ; 1872-7123
    ISSN 0925-4927 ; 0165-1781
    DOI 10.1016/j.pscychresns.2022.111561
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  9. Article ; Online: Reinforcement, dopamine and rodent models in drug development for ADHD.

    Tripp, Gail / Wickens, Jeff

    Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

    2012  Volume 9, Issue 3, Page(s) 622–634

    Abstract: Attention deficit hyperactivity disorder (ADHD) presents special challenges for drug development. Current treatment with psychostimulants and nonstimulants is effective, but their mechanism of action beyond the cellular level is incompletely understood. ... ...

    Abstract Attention deficit hyperactivity disorder (ADHD) presents special challenges for drug development. Current treatment with psychostimulants and nonstimulants is effective, but their mechanism of action beyond the cellular level is incompletely understood. We review evidence suggesting that altered reinforcement mechanisms are a fundamental characteristic of ADHD. We show that a deficit in the transfer of dopamine signals from established positive reinforcers to cues that predict such reinforcers may underlie these altered reinforcement mechanisms, and in turn explain key symptoms of ADHD. We argue that the neural substrates controlling the excitation and inhibition of dopamine neurons during the transfer process are a promising target for future drug development. There is a need to develop animal models and behavioral paradigms that can be used to experimentally investigate these mechanisms and their effects on sensitivity to reinforcement. More specific and selective targeting of drug development may be possible through this approach.
    MeSH term(s) Animals ; Attention Deficit Disorder with Hyperactivity/drug therapy ; Disease Models, Animal ; Dopamine/metabolism ; Dopamine Agents/therapeutic use ; Drug Design ; Humans ; Reinforcement, Psychology ; Rodentia
    Chemical Substances Dopamine Agents ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2012-07-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2316693-9
    ISSN 1878-7479 ; 1933-7213
    ISSN (online) 1878-7479
    ISSN 1933-7213
    DOI 10.1007/s13311-012-0132-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Input dependent cell assembly dynamics in a model of the striatal medium spiny neuron network.

    Ponzi, Adam / Wickens, Jeff

    Frontiers in systems neuroscience

    2012  Volume 6, Page(s) 6

    Abstract: The striatal medium spiny neuron (MSN) network is sparsely connected with fairly weak GABAergic collaterals receiving an excitatory glutamatergic cortical projection. Peri-stimulus time histograms (PSTH) of MSN population response investigated in various ...

    Abstract The striatal medium spiny neuron (MSN) network is sparsely connected with fairly weak GABAergic collaterals receiving an excitatory glutamatergic cortical projection. Peri-stimulus time histograms (PSTH) of MSN population response investigated in various experimental studies display strong firing rate modulations distributed throughout behavioral task epochs. In previous work we have shown by numerical simulation that sparse random networks of inhibitory spiking neurons with characteristics appropriate for UP state MSNs form cell assemblies which fire together coherently in sequences on long behaviorally relevant timescales when the network receives a fixed pattern of constant input excitation. Here we first extend that model to the case where cortical excitation is composed of many independent noisy Poisson processes and demonstrate that cell assembly dynamics is still observed when the input is sufficiently weak. However if cortical excitation strength is increased more regularly firing and completely quiescent cells are found, which depend on the cortical stimulation. Subsequently we further extend previous work to consider what happens when the excitatory input varies as it would when the animal is engaged in behavior. We investigate how sudden switches in excitation interact with network generated patterned activity. We show that sequences of cell assembly activations can be locked to the excitatory input sequence and outline the range of parameters where this behavior is shown. Model cell population PSTH display both stimulus and temporal specificity, with large population firing rate modulations locked to elapsed time from task events. Thus the random network can generate a large diversity of temporally evolving stimulus dependent responses even though the input is fixed between switches. We suggest the MSN network is well suited to the generation of such slow coherent task dependent response which could be utilized by the animal in behavior.
    Language English
    Publishing date 2012-03-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2453005-0
    ISSN 1662-5137 ; 1662-5137
    ISSN (online) 1662-5137
    ISSN 1662-5137
    DOI 10.3389/fnsys.2012.00006
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