Joshua T Dudman

Joshua T Dudman
Howard Hughes Medical Institute | HHMI · Janelia Research Campus

Ph.D., Columbia University

About

77
Publications
19,235
Reads
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4,660
Citations
Introduction
I entered college as a confused student majoring in philosophy and biology. A course in Physiological Psychology converted me to a neuroscientist. After working as a technician with Christine Konradi, I went to graduate school with Steve Siegelbaum. Befitting an erstwhile philosophy student, I have worked on a range of questions from X-ray crystallography to the function of ion channels to clinical work. My current work focuses on the role of basal ganglia in adaptive behavior in mice.
Additional affiliations
May 2013 - present
Howard Hughes Medical Institute
Position
  • Group Leader
January 2008 - May 2013
Howard Hughes Medical Institute
Position
  • Fellow
November 2006 - November 2008
Columbia University
Position
  • NRSA Postodoctoral Fellow
Education
September 2001 - September 2006
Columbia University
Field of study
  • Neurobiology and Behavior
September 1995 - December 1999
Amherst College
Field of study
  • Neuroscience

Publications

Publications (77)
Article
Full-text available
For goal-directed behaviour it is critical that we can both select the appropriate action and learn to modify the underlying movements (for example, the pitch of a note or velocity of a reach) to improve outcomes. The basal ganglia are a critical nexus where circuits necessary for the production of behaviour, such as the neocortex and thalamus, are...
Article
Full-text available
Progressive depletion of midbrain dopamine neurons (PDD) is associated with deficits in the initiation, speed, and fluidity of voluntary movement. Models of basal ganglia function focus on initiation deficits; however, it is unclear how they account for deficits in the speed or amplitude of movement (vigor). Using an effort-based operant conditioni...
Article
Full-text available
We recently demonstrated that the collaterals of substantia nigra (SN) projection neurons can implement divisive feedback inhibition, or gain control (Brown et al., 2014). While in vivo recordings were consistent with divisive feedback inhibition, a causal test was lacking. A gain control model of the nigral microcircuit implies behavioral effects...
Article
Full-text available
Midbrain dopaminergic (DA) neurons are thought to guide learning via phasic elevations of firing in response to reward predicting stimuli. The mechanism for these signals remains unclear. Using extracellular recording during associative learning, we found that inhibitory neurons in the ventral midbrain of mice responded to salient auditory stimuli...
Article
The interaction of descending neocortical outputs and subcortical premotor circuits is critical for shaping skilled movements. Two broad classes of motor cortical output projection neurons provide input to many subcortical motor areas: pyramidal tract (PT) neurons, which project throughout the neuraxis, and intratelencephalic (IT) neurons, which pr...
Article
Full-text available
Sensory cues that precede reward acquire predictive (expected value) and incentive (drive reward-seeking action) properties. Mesolimbic dopamine neurons’ responses to sensory cues correlate with both expected value and reward-seeking action. This has led to the proposal that phasic dopamine responses may be sufficient to inform value-based decision...
Preprint
Full-text available
Recent success in training artificial agents and robots derives from a combination of direct learning of behavioral policies and indirect learning via value functions. Policy learning and value learning employ distinct algorithms that depend upon evaluation of errors in performance and reward prediction errors, respectively. In animals, behavioral...
Article
Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic imp...
Article
Full-text available
Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic imp...
Preprint
Full-text available
The hippocampus encodes both spatial and non-spatial features of an environment thought to be critical to guide navigational trajectories and associative learning, respectively. These seemingly dichotomous roles have been reconciled in a proposed cognitive map - a representation of environment structure abstracted away from specific behavioral dema...
Preprint
Full-text available
The midbrain dorsal raphe (DR) and ventral tegmental area (VTA) contain two of the brain's main ascending neuromodulatory transmitters: serotonin and dopamine. We studied the pathway from DR to VTA using single-cell RNA sequencing, anatomical tracing, and electrophysiology and behavior in mice. Single-cell sequencing confirmed a differential distri...
Chapter
Optogenetic reagents allow for depolarization and hyperpolarization of cells with light. This provides unprecedented spatial and temporal resolution to the control of neuronal activity both in vitro and in vivo. In the intact animal this requires strategies to deliver light deep into the highly scattering tissue of the brain. A general approach tha...
Preprint
Full-text available
Motor cortex is a key node in the forebrain circuits that enable flexible control of limb movements. The influence of motor cortex on movement execution is primarily carried by either pyramidal tract neurons (PT), which project directly to the brainstem and spinal cord, or intratelencephalic neurons (IT), which project within the forebrain. The log...
Preprint
Full-text available
To study the dynamics of neural processing across timescales, we require the ability to follow the spiking of thousands of individually separable neurons over weeks and months, during unrestrained behavior. To address this need, we introduce the Neuropixels 2.0 probe together with novel analysis algorithms. The new probe has over 5,000 sites and is...
Article
Full-text available
Behavior is readily classified into patterns of movements with inferred common goals—actions. Goals may be discrete; movements are continuous. Through the careful study of isolated movements in laboratory settings, or via introspection, it has become clear that animals can exhibit exquisite graded specification to their movements. Moreover, graded...
Article
Full-text available
The thalamus is the central communication hub of the forebrain and provides the cerebral cortex with inputs from sensory organs, subcortical systems and the cortex itself. Multiple thalamic regions send convergent information to each cortical region, but the organizational logic of thalamic projections has remained elusive. Through comprehensive tr...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Poster
Full-text available
The learning and/or execution of motor sequences may be disrupted in disorders affecting dopamine inputs to the basal ganglia, but the neural basis of this disruption remains poorly understood. We developed a continuous movement sequence task for rodents that is learned in <300 trials and can dissociate aspects of sequence performance/execution f...
Article
Animals infer when and where a reward is available from experience with informative sensory stimuli and their own actions. In vertebrates, this is thought to depend upon the release of dopamine from midbrain dopaminergic neurons. Studies of the role of dopamine have focused almost exclusively on their encoding of informative sensory stimuli; howeve...
Preprint
Full-text available
Motor cortex is part of a network of central brain circuits that together enable robust, flexible, and efficient movement in mammals. Recent work has revealed rich dynamics in mammalian motor cortex thought to underlie robust and flexible movements. These dynamics are a consequence of recurrent connectivity between individual cortical neuron subtyp...
Article
Neuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neuron...
Article
Full-text available
Optical imaging has become a powerful tool for studying brains in vivo. The opacity of adult brains makes microendoscopy, with an optical probe such as a gradient index (GRIN) lens embedded into brain tissue to provide optical relay, the method of choice for imaging neurons and neural activity in deeply buried brain structures. Incorporating a Bess...
Article
Full-text available
Animals adapt their behavior in response to informative sensory cues using multiple brain circuits. The activity of midbrain dopaminergic neurons is thought to convey a critical teaching signal: reward-prediction error. Although reward-prediction error signals are thought to be essential to learning, little is known about the dynamic changes in the...
Article
Targeted manipulation of activity in specific populations of neurons is important for investigating the neural circuit basis of behavior. Optogenetic approaches using light-sensitive microbial rhodopsins have permitted manipulations to reach a level of temporal precision that is enabling functional circuit dissection. As demand for more precise per...
Article
Full-text available
In this Scientific Perspectives we first review the recent advances in our understanding of the functional architecture of basal ganglia circuits. Then we argue that these data can best be explained by a model in which basal ganglia act to control the gain of movement kinematics to shape performance based on prior experience, which we refer to as a...
Preprint
Full-text available
Uncovering common principles by which diverse modalities of information are processed is a fundamental goal in neuroscience. In mammalian brain, thalamus is the central processing station for inputs from sensory systems, subcortical motor systems, and cortex; a function subserved by over 30 defined nuclei 1,2 . Multiple thalamic nuclei send converg...
Preprint
Full-text available
Coherent control of purposive actions emerges from the coordination of multiple brain circuits during learning. Dissociable brain circuits and cell-types are thought to preferentially participate in distinct learning mechanisms. For example, the activity of midbrain dopamine (mDA) neurons is proposed to primarily, or even exclusively, reflect rewar...
Article
Full-text available
Dendritic release of dopamine activates dopamine D2 autoreceptors, which are inhibitory G protein-coupled receptors (GPCRs), to decrease the excitability of dopamine neurons. This study used tagged D2 receptors to identify the localization and distribution of these receptors in living midbrain dopamine neurons. GFP-tagged D2 receptors were found to...
Article
Full-text available
Behavior has molecular, cellular, and circuit determinants. However, because many proteins are broadly expressed, their acute manipulation within defined cells has been difficult. Here, we combined the speed and molecular specificity of pharmacology with the cell type specificity of genetic tools. DART (drugs acutely restricted by tethering) is a t...
Article
Efficient retrograde access to projection neurons for the delivery of sensors and effectors constitutes an important and enabling capability for neural circuit dissection. Such an approach would also be useful for gene therapy, including the treatment of neurodegenerative disorders characterized by pathological spread through functionally connected...
Article
Vertebrates are remarkable for their ability to select and execute goal-directed actions: motor skills critical for thriving in complex, competitive environments. A key aspect of a motor skill is the ability to execute its component movements over a range of speeds, amplitudes and frequencies (vigor). Recent work has indicated that a subcortical ci...
Chapter
Full-text available
The basal ganglia plays a significant role in transforming activity in the cerebral cortex into directed behavior, involving motor learning, habit formation and the selection of actions based on desirable outcomes, and the organization of the basal ganglia is intimately linked to that of the cerebral cortex. In this chapter, we focus primarily on t...
Article
Full-text available
The ability to image neurons anywhere in the mammalian brain is a major goal of optical microscopy. Here we describe a minimally invasive microendoscopy system for studying the morphology and function of neurons at depth. Utilizing a guide cannula with an ultrathin wall, we demonstrated in vivo two-photon fluorescence imaging of deeply buried nucle...
Article
Full-text available
Midbrain dopamine (DA) neurons are thought to be a critical node in the circuitry that mediates reward learning. DA neurons receive diverse inputs from regions distributed throughout the neuraxis from frontal neocortex to the mesencephalon. While a great deal is known about changes in the activity of individual DA neurons during learning, much less...
Article
Full-text available
Midbrain dopamine (DA) neurons are thought to be a critical node in the circuitry that mediates reward learning. DA neurons receive diverse inputs from regions distributed throughout the neuraxis from frontal neocortex to the mesencephalon. While a great deal is known about changes in the activity of individual DA neurons during learning, much less...
Article
Full-text available
Compared to the dorsal hippocampus, relatively few studies have characterized neuronal responses in the ventral hippocampus. In particular, it is unclear whether and how cells in the ventral region represent space and/or respond to contextual changes. We recorded from dorsal and ventral CA1 neurons in freely moving mice exposed to manipulations of...
Article
Full-text available
A number of recent studies have provided compelling demonstrations that both mice and rats can be trained to perform a variety of behavioral tasks while restrained by mechanical elements mounted to the skull. The independent development of this technique by a number of laboratories has led to diverse solutions. We found that these solutions often u...
Article
Full-text available
Animals learn both whether and when a reward will occur. Neural models of timing posit that animals learn the mean time until reward perturbed by a fixed relative uncertainty. Nonetheless, animals can learn to perform actions for reward even in highly variable natural environments. Optimal inference in the presence of variable information requires...
Article
Full-text available
The basal ganglia play a critical role in the regulation of voluntary action in vertebrates. Our understanding of the function of the basal ganglia relies heavily upon anatomical information, but continued progress will require an understanding of the specific functional roles played by diverse cell types and their connectivity. An increasing numbe...
Article
Full-text available
The transformation of synaptic input into patterns of spike output is a fundamental operation that is determined by the particular complement of ion channels that a neuron expresses. Although it is well established that individual ion channel proteins make stochastic transitions between conducting and non-conducting states, most models of synaptic...
Data
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Stochastic gating can produce substantial channel noise (0.70 MB PDF)
Data
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A regularly spiking MEC stellate neuron (0.80 MB PDF)
Data
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Membrane impedance determines the increased membrane potential fluctuations in the HCN1 knock-out model (3.38 MB PDF)
Data
Ih is not required for perithreshold oscillations (2.78 MB PDF)
Data
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Necessity and sufficiency of stochastic conductances (4.69 MB PDF)
Data
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Spiking properties of the deterministic model (0.14 MB PDF)
Data
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Partially stochastic model does not significantly differ from completely stochastic model (0.19 MB PDF)
Data
A wide range of HCN kinetics are sufficient for AHP enhancement (0.58 MB PDF)
Data
Components of the stellate model (0.18 MB PDF)
Data
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Voltage threshold for spike initiation is not correlated with ISI (0.08 MB PDF)
Data
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Determining the critical point for spike initiation (0.34 MB PDF)
Article
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Article
HCN1 hyperpolarization-activated cation channels act as an inhibitory constraint of both spatial learning and synaptic integration and long-term plasticity in the distal dendrites of hippocampal CA1 pyramidal neurons. However, as HCN1 channels provide an excitatory current, the mechanism of their inhibitory action remains unclear. Here we report th...
Article
Synaptic potentials originating at distal dendritic locations are severely attenuated when they reach the soma and, thus, are poor at driving somatic spikes. Nonetheless, distal inputs convey essential information, suggesting that such inputs may be important for compartmentalized dendritic signaling. Here we report a new plasticity rule in which s...
Article
Full-text available
Whereas recent studies have elucidated principles for representation of information within the entorhinal cortex, less is known about the molecular basis for information processing by entorhinal neurons. The HCN1 gene encodes ion channels that mediate hyperpolarization-activated currents (I(h)) that control synaptic integration and influence severa...
Article
Many organisms show an impressive capacity to store information for online recall in the performance of memory tasks (Goldman-Rakic, 1990). This rapid and temporary storage of information during an experimental trial has been called “working memory.” In many behavioral paradigms, individual cells in the prefrontal and medial temporal lobe cortices...
Article
Full-text available
Ligand-gated ion channels involved in the modulation of synaptic strength are the AMPA, kainate, and NMDA glutamate receptors. Small molecules that potentiate AMPA receptor currents relieve cognitive deficits caused by neurodegenerative diseases such as Alzheimer's disease and show promise in the treatment of depression. Previously, there has been...
Article
Molecular adaptations are believed to contribute to the mechanism of action of antipsychotic drugs (APDs). We attempted to establish common gene regulation patterns induced by chronic treatment with APDs. Gene expression analysis was performed with the Affymetrix U34A array in the frontal cortex (FC) and the striatum of rats chronically treated wit...
Article
The importance of long-term synaptic plasticity as a cellular substrate for learning and memory is well established. By contrast, little is known about how learning and memory are regulated by voltage-gated ion channels that integrate synaptic information. We investigated this question using mice with general or forebrain-restricted knockout of the...
Article
Full-text available
Responses to threat-related stimuli are influenced by conscious and unconscious processes, but the neural systems underlying these processes and their relationship to anxiety have not been clearly delineated. Using fMRI, we investigated the neural responses associated with the conscious and unconscious (backwardly masked) perception of fearful face...
Article
The importance of long-term synaptic plasticity as a cellular substrate for learning and memory is well established. By contrast, little is known about how learning and memory are regulated by voltage-gated ion channels that integrate synaptic information. We investigated this question using mice with general or forebrain-restricted knockout of the...
Article
Dopamine (DA) receptor-mediated signal transduction and gene expression play a central role in many brain disorders from schizophrenia to Parkinson's disease to addiction. While trying to evaluate the role of L-type Ca2+ channels in dopamine D1 receptor-mediated phosphorylation of the transcription factor cyclic AMP response element-binding protein...
Article
Addictive drugs such as amphetamine and cocaine stimulate the dopaminergic system, activate dopamine receptors and induce gene expression throughout the striatum. The signal transduction pathway leading from dopamine receptor stimulation at the synapse to gene expression in the nucleus has not been fully elucidated. Here, we present evidence that D...
Article
In contrast to our increasingly detailed understanding of how synaptic plasticity provides a cellular substrate for learning and memory, it is less clear how a neuron's voltage-gated ion channels interact with plastic changes in synaptic strength to influence behavior. We find, using generalized and regional knockout mice, that deletion of the HCN1...
Article
Full-text available
Enkephalin modulates striatal function, thereby affecting motor performance and addictive behaviors. The proenkephalin gene is also used as a model to study cyclic AMP-mediated gene expression in striatal neurons. The second messenger pathway leading to proenkephalin expression demonstrates how cyclic AMP pathways are synchronized with depolarizati...