@article {67951, title = {A midbrain-thalamus-cortex circuit reorganizes cortical dynamics to initiate movement.}, journal = {Cell}, volume = {185}, year = {2022}, month = {2022 Mar 17}, pages = {1065}, abstract = {

Motor behaviors are often planned long before execution but only released after specific sensory events. Planning and execution are each associated with distinct patterns of motor cortex activity. Key questions are how these dynamic activity patterns are generated and how they relate to behavior. Here, we investigate the multi-regional neural circuits that link an auditory "Go cue" and the transition from planning to execution of directional licking. Ascending glutamatergic neurons in the midbrain reticular and pedunculopontine nuclei show short latency and phasic changes in spike rate that are selective for the Go cue. This signal is transmitted via the thalamus to the motor cortex, where it triggers a rapid reorganization of motor cortex state from planning-related activity to a motor command, which in turn drives appropriate movement. Our studies show how midbrain can control cortical dynamics via the thalamus for rapid and precise motor behavior.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2022.02.006}, author = {Inagaki, Hidehiko K and Chen, Susu and Ridder, Margreet C and Sah, Pankaj and Li, Nuo and Yang, Zidan and Hasanbegovic, Hana and Gao, Zhenyu and Gerfen, Charles R and Svoboda, Karel} } @article {49061, title = {Cell type-specific variation of somatotopic precision across corticostriatal projections. }, journal = {bioRxiv}, year = {2018}, month = {2018 Feb 7}, abstract = {

The striatum shows general topographic organization and regional differences in behavioral functions. How corticostriatal topography differs across cortical areas and cell types to support these distinct functions is unclear. This study contrasted corticostriatal projections from two layer 5 cell types, intratelencephalic (IT-type) and pyramidal tract (PT-type) neurons, using viral vectors expressing fluorescent reporters in Cre-driver mice. Long-range corticostriatal projections from sensory and motor cortex are somatotopic, with a decreasing somatotopic specificity as injections move from sensory to motor and frontal areas. Somatotopic organization differs between IT-type and PT-type neurons, including injections in the same site, with IT-type neurons having higher somatotopic stereotypy than PT-type neurons. Furthermore, IT-type projections from interconnected cortical areas have stronger correlations in corticostriatal targeting than PT-type projections do. Thus, as predicted by a long-standing basal ganglia model, corticostriatal projections of interconnected cortical areas form parallel circuits in basal ganglia-thalamus-cortex loops.

}, doi = {10.1101/261446}, author = {Hooks, Bryan M and Papale, Andrew E and Paletzki, Ronald and Feroze, Muhammad and Eastwood, Brian S and Couey, Jonathan J and Winnubst, Johan and Chandrashekar, Jayaram and Gerfen, Charles R} } @article {49496, title = {Distinct descending motor cortex pathways and their roles in movement.}, journal = {Nature}, volume = {563}, year = {2018}, month = {2018 Nov}, pages = {79-84}, abstract = {

Activity in the motor cortex predicts movements, seconds before they are initiated. This preparatory activity has been observed across cortical layers, including in descending pyramidal tract neurons in layer 5. A key question is how preparatory activity is maintained without causing movement, and is ultimately converted to a motor command to trigger appropriate movements. Here, using single-cell transcriptional profiling and axonal reconstructions, we identify two types of pyramidal tract neuron. Both types project to several targets in the basal ganglia and brainstem. One type projects to thalamic regions that connect back to motor cortex; populations of these neurons produced early preparatory activity that persisted until the movement was initiated. The second type projects to motor centres in the medulla and mainly\ produced late preparatory activity and motor commands. These results indicate that two types of motor cortex output neurons have specialized roles in motor control.

}, issn = {1476-4687}, doi = {10.1038/s41586-018-0642-9}, author = {Economo, Michael N and Viswanathan, Sarada and Tasic, Bosiljka and Bas, Erhan and Winnubst, Johan and Menon, Vilas and Graybuck, Lucas T and Nguyen, Thuc Nghi and Smith, Kimberly A and Yao, Zizhen and Wang, Lihua and Gerfen, Charles R and Chandrashekar, Jayaram and Zeng, Hongkui and Looger, Loren L and Svoboda, Karel} } @article {49413, title = {Topographic precision in sensory and motor corticostriatal projections varies across cell type and cortical area.}, journal = {Nature Communications}, volume = {9}, year = {2018}, month = {2018 Sep 03}, pages = {3549}, abstract = {

The striatum shows general topographic organization and regional differences in behavioral functions. How corticostriatal topography differs across cortical areas and cell types to support these distinct functions is unclear. This study contrasted corticostriatal projections from two layer 5 cell types, intratelencephalic (IT-type) and pyramidal tract (PT-type) neurons, using viral vectors expressing fluorescent reporters in Cre-driver mice. Corticostriatal projections from sensory and motor cortex are somatotopic, with a decreasing topographic specificity as injection sites move from sensory to motor and frontal areas. Topographic organization differs between IT-type and PT-type neurons, including injections in the same site, with IT-type neurons having higher topographic stereotypy than PT-type neurons. Furthermore, IT-type projections from interconnected cortical areas have stronger correlations in corticostriatal targeting than PT-type projections do. As predicted by a longstanding model, corticostriatal projections of interconnected cortical areas form parallel circuits in the basal ganglia.

}, issn = {2041-1723}, doi = {10.1038/s41467-018-05780-7}, author = {Hooks, Bryan M and Papale, Andrew E and Paletzki, Ronald F and Feroze, Muhammad W and Eastwood, Brian S and Couey, Jonathan J and Winnubst, Johan and Chandrashekar, Jayaram and Gerfen, Charles R} } @article {48459, title = {Maintenance of persistent activity in a frontal thalamocortical loop.}, journal = {Nature}, volume = {545}, year = {2017}, month = {2017 May 03}, pages = {181-6}, abstract = {

Persistent neural activity maintains information that connects past and future events. Models of persistent activity often invoke reverberations within local cortical circuits, but long-range circuits could also contribute. Neurons in the mouse anterior lateral motor cortex (ALM) have been shown to have selective persistent activity that instructs future actions. The ALM is connected bidirectionally with parts of the thalamus, including the ventral medial and ventral anterior-lateral nuclei. We recorded spikes from the ALM and thalamus during tactile discrimination with a delayed directional response. Here we show that, similar to ALM neurons, thalamic neurons exhibited selective persistent delay activity that predicted movement direction. Unilateral photoinhibition of delay activity in the ALM or thalamus produced contralesional neglect. Photoinhibition of the thalamus caused a short-latency and near-complete collapse of ALM activity. Similarly, photoinhibition of the ALM diminished thalamic activity. Our results show that the thalamus is a circuit hub in motor preparation and suggest that persistent activity requires reciprocal excitation across multiple brain areas.

}, issn = {1476-4687}, doi = {10.1038/nature22324}, author = {Guo, Zengcai V and Inagaki, Hidehiko K and Daie, Kayvon and Druckmann, Shaul and Gerfen, Charles R and Svoboda, Karel} } @article {47934, title = {A designer AAV variant permits efficient retrograde access to projection neurons.}, journal = {Neuron}, volume = {92}, year = {2016}, month = {2016 Oct 19}, pages = {372-82}, abstract = {

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 and highly distributed networks. Viral vectors, in particular, are powerful gene delivery vehicles for the nervous system, but all available tools suffer from inefficient retrograde transport or limited clinical potential. To address this need, we applied in\ vivo directed evolution to engineer potent retrograde functionality into the capsid of adeno-associated virus (AAV), a vector that has shown promise in neuroscience research and the clinic. A newly evolved variant, rAAV2-retro, permits robust retrograde access to projection neurons with efficiency comparable to classical synthetic retrograde tracers and enables sufficient sensor/effector expression for functional circuit interrogation and in\ vivo genome editing in targeted neuronal populations. VIDEO ABSTRACT.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2016.09.021}, author = {Tervo, D Gowanlock R and Hwang, Bum-Yeol and Viswanathan, Sarada and Gaj, Thomas and Lavzin, Maria and Ritola, Kimberly D and Lindo, Sarah and Michael, Susan and Kuleshova, Elena and Ojala, David and Huang, Cheng-Chiu and Gerfen, Charles R and Schiller, Jackie and Dudman, Joshua T and Hantman, Adam W and Looger, Loren L and Schaffer, David V and Karpova, Alla Y} } @article {48044, title = {Long distance projections of cortical pyramidal neurons.}, journal = {Journal of Neuroscience Research}, year = {2016}, month = {2016 Nov 12}, abstract = {

The neuronal circuits defined by the axonal projections of pyramidal neurons in the cerebral cortex are responsible for processing sensory and other information to plan and execute behavior. Subtypes of cortical pyramidal neurons are organized across layers, with those in different layers distinguished by their patterns of axonal projections and connectivity. For example, those in layers 2 and 3 project between cortical areas to integrate sensory and other information with motor areas; while those in layers 5 and 6 also integrate information between cortical areas, but also project to subcortical structures involved in the generation of behavior. Recent advances in neuroanatomical techniques allow one to target specific subtypes of cortical pyramidal neurons and label both their inputs and projections. Combining these methods with neurophysiological recording techniques and newly introduced atlases of the mouse brain provide the opportunity to achieve a detailed view of the organization of cerebral cortical circuits.

}, doi = {10.1002/jnr.23978}, author = {Gerfen, Charles R and Economo, Michael N and Chandrashekar, Jayaram} } @article {47274, title = {A platform for brain-wide imaging and reconstruction of individual neurons.}, journal = {eLife}, volume = {5}, year = {2016}, month = {2016 Jan 20}, abstract = {

The structure of axonal arbors controls how signals from individual neurons are routed within the mammalian brain. However, the arbors of very few long-range projection neurons have been reconstructed in their entirety, as axons with diameters as small as 100 nm arborize in target regions dispersed over many millimeters of tissue. We introduce a platform for high-resolution, three-dimensional fluorescence imaging of complete tissue volumes that enables the visualization and reconstruction of long-range axonal arbors. This platform relies on a high-speed two-photon microscope integrated with a tissue vibratome and a suite of computational tools for large-scale image data. We demonstrate the power of this approach by reconstructing the axonal arbors of multiple neurons in the motor cortex across a single mouse brain.

}, issn = {2050-084X}, doi = {10.7554/eLife.10566}, author = {Economo, Michael N and Clack, Nathan G and Lavis, Luke D and Gerfen, Charles R and Svoboda, Karel and Myers, Eugene W and Chandrashekar, Jayaram} } @article {46576, title = {High-performance probes for light and electron microscopy.}, journal = {Nature Methods}, volume = {12}, year = {2015}, month = {2015 Apr 27}, pages = {568-76}, abstract = {

We describe an engineered family of highly antigenic molecules based on GFP-like fluorescent proteins. These molecules contain numerous copies of peptide epitopes and simultaneously bind IgG antibodies at each location. These {\textquoteright}spaghetti monster{\textquoteright} fluorescent proteins (smFPs) distributed well in neurons, notably into small dendrites, spines and axons. smFP immunolabeling localized weakly expressed proteins not well resolved with traditional epitope tags. By varying epitope and scaffold, we generated a diverse family of mutually orthogonal antigens. In cultured neurons and mouse and fly brains, smFP probes allowed robust, orthogonal multicolor visualization of proteins, cell populations and neuropil. smFP variants complement existing tracers and greatly increase the number of simultaneous imaging channels, and they performed well in advanced preparations such as array tomography, super-resolution fluorescence imaging and electron microscopy. In living cells, the probes improved single-molecule image tracking and increased yield for RNA-seq. These probes facilitate new experiments in connectomics, transcriptomics and protein localization.

}, issn = {1548-7105}, doi = {10.1038/nmeth.3365}, author = {Viswanathan, Sarada and Williams, Megan E. and Bloss, Erik B. and Stasevich, Timothy J. and Speer, Colenso M. and Nern, Aljoscha and Pfeiffer, Barret D. and Hooks, Bryan M. and Li, Wei-Ping and English, Brian P. and Tian, Teresa and Henry, Gilbert L. and Macklin, John J. and Patel, Ronak and Gerfen, Charles R and Zhuang, Xiaowei and Wang, Yalin and Rubin, Gerald M and Looger, Loren L} }