Motor cortical inactivation impairs corrective submovements in mice performing a hold-still center-out reach task.

Holding still and aiming reaches to spatial targets may depend on distinct neural circuits. Using automated homecage training and a sensitive joystick, we trained freely-moving mice to contact a joystick, hold their forelimb still, and then reach to rewarded target locations. Mice learned the task by initiating forelimb sequences with clearly resolved submillimeter-scale micromovements followed by millimeter-scale reaches to learned spatial targets. Hundreds of thousands of trajectories were decomposed into millions of kinematic submovements, while photoinhibition was used to test roles of motor cortical areas. Inactivation of both caudal and rostral forelimb areas preserved the ability to produce aimed reaches, but reduced reach speed. Inactivation specifically of contralateral caudal forelimb area (CFA) additionally impaired the ability to aim corrective submovements to remembered locations following target undershoots. Our findings show that motor cortical inactivations reduce the gain of forelimb movements but that inactivation specifically of contralateral CFA impairs corrective movements important for reaching a target location.

Cortex-dependent corrections as the tongue reaches for and misses targets.

Precise tongue control is necessary for drinking, eating and vocalizing1-3. However, because tongue movements are fast and difficult to resolve, neural control of lingual kinematics remains poorly understood. Here we combine kilohertz-frame-rate imaging and a deep-learning-based neural network to resolve 3D tongue kinematics in mice drinking from a water spout. Successful licks required corrective submovements that-similar to online corrections during primate reaches4-11-occurred after the tongue missed unseen, distant or displaced targets. Photoinhibition of anterolateral motor cortex impaired corrections, which resulted in hypometric licks that missed the spout. Neural activity in anterolateral motor cortex reflected upcoming, ongoing and past corrective submovements, as well as errors in predicted spout contact. Although less than a tenth of a second in duration, a single mouse lick exhibits the hallmarks of online motor control associated with a primate reach, including cortex-dependent corrections after misses.

Automated home cage training of mice in a hold-still center-out reach task.

An obstacle to understanding neural mechanisms of movement is the complex, distributed nature of the mammalian motor system. Here we present a novel behavioral paradigm for high-throughput dissection of neural circuits underlying mouse forelimb control. Custom touch-sensing joysticks were used to quantify mouse forelimb trajectories with micron-millisecond spatiotemporal resolution. Joysticks were integrated into computer-controlled, rack-mountable home cages, enabling batches of mice to be trained in parallel. Closed loop behavioral analysis enabled online control of reward delivery for automated training. We used this system to show that mice can learn, with no human handling, a direction-specific hold-still center-out reach task in which a mouse first held its right forepaw still before reaching out to learned spatial targets. Stabilogram diffusion analysis of submillimeter-scale micromovements produced during the hold demonstrate that an active control process, akin to upright balance, was implemented to maintain forepaw stability. Trajectory decomposition methods, previously used in primates, were used to segment hundreds of thousands of forelimb trajectories into millions of constituent kinematic primitives. This system enables rapid dissection of neural circuits for controlling motion primitives from which forelimb sequences are built. NEW & NOTEWORTHY A novel joystick design resolves mouse forelimb kinematics with micron-millisecond precision. Home cage training is used to train mice in a hold-still center-out reach task. Analytical methods, previously used in primates, are used to decompose mouse forelimb trajectories into kinematic primitives.

A Stable Neural Code for Birdsong.

Proteins, synapses, and neural connections are in constant flux, yet motor behaviors somehow remain stable. In this issue of Neuron, Katlowitz et al. (2018) show that temporally precise neural activity driving birdsong production is stable for weeks.

Experimentally constrained circuit model of cortical arteriole networks for understanding flow redistribution due to occlusion and neural activation.

Computations are described which estimate flows in all branches of the cortical surface arteriole network from two-photon excited fluorescence (2PEF) microscopy images which provide the network topology and, in selected branches red blood cell (RBC) speeds and lumen diameters. Validation is done by comparing the flow predicted by the model with experimentally measured flows and by comparing the predicted flow redistribution in the network due to single-vessel strokes with experimental observations. The model predicts that tissue is protected from RBC flow decreases caused by multiple occlusions of surface arterioles but not penetrating arterioles. The model can also be used to study flow rerouting due to vessel dilations and constrictions.

Origins of basal ganglia output signals in singing juvenile birds.

Across species, complex circuits inside the basal ganglia (BG) converge on pallidal output neurons that exhibit movement-locked firing patterns. Yet the origins of these firing patterns remain poorly understood. In songbirds during vocal babbling, BG output neurons homologous to those found in the primate internal pallidal segment are uniformly activated in the tens of milliseconds prior to syllable onsets. To test the origins of this remarkably homogenous BG output signal, we recorded from diverse upstream BG cell types during babbling. Prior to syllable onsets, at the same time that internal pallidal segment-like neurons were activated, putative medium spiny neurons, fast spiking and tonically active interneurons also exhibited transient rate increases. In contrast, pallidal neurons homologous to those found in primate external pallidal segment exhibited transient rate decreases. To test origins of these signals, we performed recordings following lesion of corticostriatal inputs from premotor nucleus HVC. HVC lesions largely abolished these syllable-locked signals. Altogether, these findings indicate a striking homogeneity of syllable timing signals in the songbird BG during babbling and are consistent with a role for the indirect and hyperdirect pathways in transforming cortical inputs into BG outputs during an exploratory behavior.