Optogenetic perturbations

Neural dynamics represent the hard-to-interpret substrate of circuit computations. Advances in large-scale recordings have highlighted the sheer spatiotemporal complexity of circuit dynamics within and across circuits, portraying in detail the difficulty of interpreting such dynamics and relating it to computation. Indeed, even in extremely simplified experimental conditions, one observes high-dimensional temporal dynamics in the relevant circuits. This complexity can be potentially addressed by the notion that not all changes in population activity have equal meaning, i.e., a small change in

…capture the effects of cell-specific optogenetic perturbations on neural activity and behavior. To address this gap, we introduce the "cell-type dynamical systems" (CTDS) model, which extends latent linear dynamical systems to contain distinct latent variables for each cell

Most brain functions rely on constant interactions among specialized brain areas. In primates, synchronized oscillations in distinct frequency bands have been suggested to facilitate the routing of feedforward and feedback signals across hierarchically organized visual areas. However, the underlying mechanisms remain largely unknown. Previous studies in mice identified two distinct visually induced gamma rhythms: a luminance-dependent narrowband high gamma rhythm (~60Hz) in both V1 and higher visual areas and a context-dependent low gamma rhythm (~30Hz) in V1. Our analysis of the open-source A

Motor cortex (MCtx) comprise the primary descending circuits for flexible control of voluntary movements and plays an important role in motor skill learning. The proposed mechanism for motor learning and updating is dopaminergic modulation of local neuronal activity. However, little is known about the organization of dopaminoceptive circuits in the MCtx. Therefore, we targeted cells expressing D1 and D2 receptors in the MCtx and discovered that neurons located in the superficial layer 2/3 have D2 receptors, whereas the majority of cells in deep output layers 5-6 express D1 receptors. We then i

…imaging, fiber photometry, and optogenetic perturbations in awake, behaving mice. Multi-modal recording of single units and local field potentials across cortex, hippocampus and thalamus alongside calcium activity via GCaMP6F in cortical neurons in triple-transgenic animals or in hippocampal astrocytes via viral transduction are brought to bear to reveal hitherto inaccessible and under-appreciated a

Task-related neural activity is widespread across populations of neurons during goal-directed behaviors. However, little is known about the synaptic reorganization and circuit mechanisms that lead to broad activity changes. Here we trained a limited subset of neurons in a spiking network with strong synaptic interactions to reproduce the activity of neurons in the motor cortex during a decision-making task. We found that task-related activity, resembling the neural data, emerged across the network, even in the untrained neurons. Analysis of trained networks showed that strong untrained synapse

Walking is a familiar but complex behavior, requiring the continuous coordination of multiple muscles while integrating proprioceptive feedback to correct for unanticipated disturbances. Although a variety of walking models propose mechanisms for this coordination, the neural computations proposed by these models have yet to be experimentally validated. Two crucial barriers are (1) gaps in modeling approaches that integrate specific neural dynamics with realistic kinematics to connect predictions to observations and (2) the inherent difficulty in perturbing or recording from neurons during wal

The ability to reach, grasp, and manipulate objects is a remarkable expression of motor skill, and the loss of this ability in injury, stroke, or disease can be devastating. These behaviors are controlled by the coordinated activity of tens of millions of neurons distributed across many CNS regions, including the primary motor cortex. While many studies have characterized the activity of single cortical neurons during reaching, the principles governing the dynamics of large, distributed neural populations remain largely unknown. Recent work in primates has suggested that during the execution o