@article {49597, title = {High-throughput synapse-resolving two-photon fluorescence microendoscopy for deep-brain volumetric imaging .}, journal = {eLife}, volume = {8}, year = {2019}, month = {2019 Jan 03}, abstract = {

Optical imaging has become a powerful tool for studying brains . 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 Bessel focus scanning module into two-photon fluorescence microendoscopy, we extended the excitation focus axially and improved its lateral resolution. Scanning the Bessel focus in 2D, we imaged volumes of neurons at high-throughput while resolving fine structures such as synaptic terminals. We applied this approach to the volumetric anatomical imaging of dendritic spines and axonal boutons in the mouse hippocampus, and functional imaging of GABAergic neurons in the mouse lateral hypothalamus .

}, issn = {2050-084X}, doi = {10.7554/eLife.40805}, author = {Meng, Guanghan and Liang, Yajie and Sarsfield, Sarah and Jiang, Wan-Chen and Lu, Rongwen and Dudman, Joshua Tate and Aponte, Yeka and Ji, Na} } @article {49122, title = {A proposed circuit computation in basal ganglia: History-dependent gain.}, journal = {Movement Disorders : official journal of the Movement Disorder Society}, year = {2018}, month = {2018 Mar 24}, abstract = {

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 history-dependent gain computation. Finally, we discuss how insights from the history-dependent gain model might translate from the bench to the bedside, primarily the implications for the design of adaptive deep brain stimulation. Thus, we explicate the key empirical and conceptual support for a normative, computational model with substantial explanatory power for the broad role of basal ganglia circuits in health and disease. {\textcopyright} 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

}, issn = {1531-8257}, doi = {10.1002/mds.27321}, author = {Yttri, Eric Allen and Dudman, Joshua Tate} } @article {45178, title = {The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output.}, journal = {eLife}, volume = {3}, year = {2014}, month = {2014 May 21}, pages = {e02397}, abstract = {

Dysfunction of the basal ganglia produces severe deficits in the timing, initiation, and vigor of movement. These diverse impairments suggest a control system gone awry. In engineered systems, feedback is critical for control. By contrast, models of the basal ganglia highlight feedforward circuitry and ignore intrinsic feedback circuits. In this study, we show that feedback via axon collaterals of substantia nigra projection neurons control the gain of the basal ganglia output. Through a combination of physiology, optogenetics, anatomy, and circuit mapping, we elaborate a general circuit mechanism for gain control in a microcircuit lacking interneurons. Our data suggest that diverse tonic firing rates, weak unitary connections and a spatially diffuse collateral circuit with distinct topography and kinetics from feedforward input is sufficient to implement divisive feedback inhibition. The importance of feedback for engineered systems implies that the intranigral microcircuit, despite its absence from canonical models, could be essential to basal ganglia function. DOI: http://dx.doi.org/10.7554/eLife.02397.001.

}, issn = {2050-084X}, doi = {10.7554/eLife.02397}, author = {Brown, Jennifer and Pan, Wei-Xing and Dudman, Joshua Tate} } @article {6485, title = {Mice infer probabilistic models for timing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, year = {2013}, month = {2013 Sep 30}, pages = {17154-9}, abstract = {

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 probabilistic models, yet it is unclear whether animals can infer such models for reward timing. Here, we develop a behavioral paradigm in which optimal performance required knowledge of the distribution from which reward delays were chosen. We found that mice were able to accurately adjust their behavior to the SD of the reward delay distribution. Importantly, mice were able to flexibly adjust the amount of prior information used for inference according to the moment-by-moment demands of the task. The ability to infer probabilistic models for timing may allow mice to adapt to complex and dynamic natural environments.

}, issn = {1091-6490}, doi = {10.1073/pnas.1310666110}, author = {Li, Yi and Dudman, Joshua Tate} } @article {5539, title = {Neural signals of extinction in the inhibitory microcircuit of the ventral midbrain.}, journal = {Nature Neuroscience}, volume = {16}, year = {2013}, month = {2013 Jan}, pages = {71-8}, abstract = {

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 with a burst of activity that occurred before the onset of the phasic response of DA neurons. This population of inhibitory neurons exhibited enhanced responses during extinction and was anticorrelated with the phasic response of simultaneously recorded DA neurons. Optogenetic stimulation revealed that this population was, in part, derived from inhibitory projection neurons of the substantia nigra that provide a robust monosynaptic inhibition of DA neurons. Thus, our results elaborate on the dynamic upstream circuits that shape the phasic activity of DA neurons and suggest that the inhibitory microcircuit of the midbrain is critical for new learning in extinction.

}, issn = {1546-1726}, doi = {10.1038/nn.3283}, author = {Pan, Wei-Xing and Brown, Jennifer and Dudman, Joshua Tate} }