@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 {67965, title = {Neural Algorithms and Circuits for Motor Planning.}, journal = {Annual Reviews Neuroscience}, year = {2022}, month = {2022 Feb 22}, abstract = {

The brain plans and executes volitional movements. The underlying patterns of neural population activity have been explored in the context of movements of the eyes, limbs, tongue, and head in nonhuman primates and rodents. How do networks of neurons produce the slow neural dynamics that prepare specific movements and the fast dynamics that ultimately initiate these movements? Recent work exploits rapid and calibrated perturbations of neural activity to test specific dynamical systems models that are capable of producing the observed neural activity. These joint experimental and computational studies show that cortical dynamics during motor planning reflect fixed points of neural activity (attractors). Subcortical control signals reshape and move attractors over multiple timescales, causing commitment to specific actions and rapid transitions to movement execution. Experiments in rodents are beginning to reveal how these algorithms are implemented at the level of brain-wide neural circuits. Expected final online publication date for the , Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

}, issn = {1545-4126}, doi = {10.1146/annurev-neuro-092021-121730}, author = {Inagaki, Hidehiko K and Chen, Susu and Daie, Kayvon and Finklestein, Arseny and Fontolan, Lorenzo and Romani, Sandro and Svoboda, Karel} } @article {68224, title = {Neural Algorithms and Circuits for Motor Planning.}, journal = {Annual Review Neuroscience}, volume = {45}, year = {2022}, month = {2022 Jul 08}, pages = {249-271}, abstract = {

The brain plans and executes volitional movements. The underlying patterns of neural population activity have been explored in the context of movements of the eyes, limbs, tongue, and head in nonhuman primates and rodents. How do networks of neurons produce the slow neural dynamics that prepare specific movements and the fast dynamics that ultimately initiate these movements? Recent work exploits rapid and calibrated perturbations of neural activity to test specific dynamical systems models that are capable of producing the observed neural activity. These joint experimental and computational studies show that cortical dynamics during motor planning reflect fixed points of neural activity (attractors). Subcortical control signals reshape and move attractors over multiple timescales, causing commitment to specific actions and rapid transitions to movement execution. Experiments in rodents are beginning to reveal how these algorithms are implemented at the level of brain-wide neural circuits.

}, keywords = {Algorithms, Animals, Brain, Motor Cortex, Movement, Neurons}, issn = {1545-4126}, doi = {10.1146/annurev-neuro-092021-121730}, author = {Inagaki, Hidehiko K and Chen, Susu and Daie, Kayvon and Finkelstein, Arseny and Fontolan, Lorenzo and Romani, Sandro and Svoboda, Karel} } @article {64781, title = {Discrete attractor dynamics underlies persistent activity in the frontal cortex.}, journal = {Nature}, volume = {566}, year = {2019}, month = {2019 Feb 06}, pages = {212-7}, abstract = {

Short-term memories link events separated in time, such as past sensation and future actions. Short-term memories are correlated with slow neural dynamics, including selective persistent activity, which can be maintained over seconds. In a delayed response task that requires short-term memory, neurons in the mouse anterior lateral motor cortex (ALM) show persistent activity that instructs future actions. To determine the principles that underlie this persistent activity, here we combined intracellular and extracellular electrophysiology with optogenetic perturbations and network modelling. We show that during the delay epoch, the activity of ALM neurons moved towards discrete end points that correspond to specific movement directions. These end points were robust to transient shifts in ALM activity caused by optogenetic perturbations. Perturbations occasionally switched the population dynamics to the other end point, followed by incorrect actions. Our results show that discrete attractor dynamics underlie short-term memory related to motor planning.

}, issn = {1476-4687}, doi = {10.1038/s41586-019-0919-7}, author = {Inagaki, Hidehiko K and Fontolan, Lorenzo and Romani, Sandro and Svoboda, Karel} } @article {65226, title = {Spatiotemporal constraints on optogenetic inactivation in cortical circuits.}, journal = {eLife}, volume = {8}, year = {2019}, month = {2019 Nov 18}, abstract = {

Optogenetics allows manipulations of genetically and spatially defined neuronal populations with excellent temporal control. However, neurons are coupled with other neurons over multiple length scales, and the effects of localized manipulations thus spread beyond the targeted neurons. We benchmarked several optogenetic methods to inactivate small regions of neocortex. Optogenetic excitation of GABAergic neurons produced more effective inactivation than light-gated ion pumps. Transgenic mice expressing the light-dependent chloride channel GtACR1 produced the most potent inactivation. Generally, inactivation spread substantially beyond the photostimulation light, caused by strong coupling between cortical neurons. Over some range of light intensity, optogenetic excitation of inhibitory neurons reduced activity in these neurons, together with pyramidal neurons, a signature of inhibition-stabilized neural networks ({\textquoteright}paradoxical effect{\textquoteright}). The offset of optogenetic inactivation was followed by rebound excitation in a light dose-dependent manner, limiting temporal resolution. Our data offer guidance for the design of optogenetics experiments.

}, issn = {2050-084X}, doi = {10.7554/eLife.48622}, author = {Li, Nuo and Chen, Susu and Guo, Zengcai V and Chen, Han and Huo, Yan and Inagaki, Hidehiko K and Chen, Guang and Davis, Courtney and Hansel, David and Guo, Caiying and Svoboda, Karel} } @article {49124, title = {Low-dimensional and monotonic preparatory activity in mouse anterior lateral motor cortex.}, journal = {The Journal of Neuroscience : the official journal of the Society for Neuroscience}, volume = {38}, year = {2018}, month = {2018 Apr 25}, pages = {4163-85}, abstract = {

Neurons in multiple brain regions fire trains of action potentials anticipating specific movements, but this {\textquoteright}preparatory activity{\textquoteright} has not been systematically compared across behavioral tasks. We compared preparatory activity in auditory and tactile delayed-response tasks in male mice. Skilled, directional licking was the motor output. The anterior lateral motor cortex (ALM) is necessary for motor planning in both tasks. Multiple features of ALM preparatory activity during the delay epoch were similar across tasks. First, majority of neurons showed direction-selective activity and spatially intermingled neurons were selective for either movement direction. Second, many cells showed mixed coding of sensory stimulus and licking direction, with a bias toward licking direction. Third, delay activity was monotonic and low-dimensional. Fourth, pairs of neurons with similar direction selectivity showed high spike-count correlations. Our study forms the foundation to analyze the neural circuit mechanisms underlying preparatory activity in a genetically tractable model organism.Short-term memories link events separated in time. Neurons in frontal cortex fire trains of action potentials anticipating specific movements, often seconds before the movement. This {\textquoteright}preparatory activity{\textquoteright} has been observed in multiple brain regions, but has rarely been compared systematically across behavioral tasks in the same brain region. To identify common features of preparatory activity, we developed and compared preparatory activity in auditory and tactile delayed-response tasks in mice. The same cortical area is necessary for both tasks. Multiple features of preparatory activity, measured with high-density silicon probes, were similar across tasks. We find that preparatory activity is low-dimensional and monotonic. Our study forms the foundation to analyze the circuit mechanisms underlying preparatory activity in a genetically tractable model organism.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.3152-17.2018}, author = {Inagaki, Hidehiko K and Inagaki, Miho and Romani, Sandro and Svoboda, Karel} } @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 {47304, title = {P1 interneurons promote a persistent internal state that enhances inter-male aggression in Drosophila.}, journal = {eLife}, volume = {4}, year = {2015}, month = {2015 Dec 29}, abstract = {

How brains are hardwired to produce aggressive behavior, and how aggression circuits are related to those that mediate courtship, is not well understood. A large-scale screen for aggression-promoting neurons in Drosophila identified several independent hits that enhanced both inter-male aggression and courtship. Genetic intersections revealed that 8-10 P1 interneurons, previously thought to exclusively control male courtship, were sufficient to promote fighting. Optogenetic experiments indicated that P1 activation could promote aggression at a threshold below that required for wing extension. P1 activation in the absence of wing extension triggered persistent aggression via an internal state that could endure for minutes. High-frequency P1 activation promoted wing extension and suppressed aggression during photostimulation, whereas aggression resumed and wing extension was inhibited following photostimulation offset. Thus, P1 neuron activation promotes a latent, internal state that facilitates aggression and courtship, and controls the overt expression of these social behaviors in a threshold-dependent, inverse manner.

}, issn = {2050-084X}, doi = {10.7554/eLife.11346}, author = {Hoopfer, Eric D and Jung, Yonil and Inagaki, Hidehiko K and Rubin, Gerald M and Anderson, David J} }