The sensory representation of causally controlled objects.

Intentional control over external objects is informed by our sensory experience of them. To study how causal relationships are learned and effected, we devised a brain machine interface (BMI) task using wide-field calcium signals. Mice learned to entrain activity patterns in arbitrary pairs of cortical regions to guide a visual cursor to a target location for reward. Brain areas that were normally correlated could be rapidly reconfigured to exert control over the cursor in a sensory-feedback-dependent manner. Higher visual cortex was more engaged when expert but not naive animals controlled the cursor. Individual neurons in higher visual cortex responded more strongly to the cursor when mice controlled it than when they passively viewed it, with the greatest response boosting as the cursor approached the target location. Thus, representations of causally controlled objects are sensitive to intention and proximity to the subject's goal, potentially strengthening sensory feedback to allow more fluent control.

Locomotion-dependent remapping of distributed cortical networks.

The interactions between neocortical areas are fluid and state-dependent, but how individual neurons couple to cortex-wide network dynamics remains poorly understood. We correlated the spiking of neurons in primary visual (V1) and retrosplenial (RSP) cortex to activity across dorsal cortex, recorded simultaneously by widefield calcium imaging. Neurons were correlated with distinct and reproducible patterns of activity across the cortical surface; while some fired predominantly with their local area, others coupled to activity in distal areas. The extent of distal coupling was predicted by how strongly neurons correlated with the local network. Changes in brain state triggered by locomotion strengthened affiliations of V1 neurons with higher visual and motor areas, while strengthening distal affiliations of RSP neurons with sensory cortices. Thus, the diverse coupling of individual neurons to cortex-wide activity patterns is restructured by running in an area-specific manner, resulting in a shift in the mode of cortical processing during locomotion.

Structure of a single whisker representation in layer 2 of mouse somatosensory cortex.

Layer (L)2 is a major output of primary sensory cortex that exhibits very sparse spiking, but the structure of sensory representation in L2 is not well understood. We combined two-photon calcium imaging with deflection of many whiskers to map whisker receptive fields, characterize sparse coding, and quantitatively define the point representation in L2 of mouse somatosensory cortex. Neurons within a column-sized imaging field showed surprisingly heterogeneous, salt-and-pepper tuning to many different whiskers. Single whisker deflection elicited low-probability spikes in highly distributed, shifting neural ensembles spanning multiple cortical columns. Whisker-evoked response probability correlated strongly with spontaneous firing rate, but weakly with tuning properties, indicating a spectrum of inherent responsiveness across pyramidal cells. L2 neurons projecting to motor and secondary somatosensory cortex differed in whisker tuning and responsiveness, and carried different amounts of information about columnar whisker deflection. From these data, we derive a quantitative, fine-scale picture of the distributed point representation in L2.

Cellular mechanisms for response heterogeneity among L2/3 pyramidal cells in whisker somatosensory cortex.

Whisker deflection evokes sparse, low-probability spiking among L2/3 pyramidal cells in rodent somatosensory cortex (S1), with spiking distributed nonuniformly between more and less responsive cells. The cellular and local circuit factors that determine whisker responsiveness across neurons are unclear. To identify these factors, we used two-photon calcium imaging and loose-seal recording to identify more and less responsive L2/3 neurons in S1 slices in vitro, during feedforward recruitment of the L2/3 network by L4 stimulation. We observed a broad gradient of spike recruitment thresholds within local L2/3 populations, with low- and high-threshold cells intermixed. This recruitment gradient was significantly correlated across different L4 stimulation sites, and between L4-evoked and whisker-evoked responses in vivo, indicating that a substantial component of responsiveness is independent of tuning to specific feedforward inputs. Low- and high-threshold L2/3 pyramidal cells differed in L4-evoked excitatory synaptic conductance and intrinsic excitability, including spike threshold and the likelihood of doublet spike bursts. A gradient of intrinsic excitability was observed across neurons. Cells that spiked most readily to L4 stimulation received the most synaptic excitation but had the lowest intrinsic excitability. Low- and high-threshold cells did not differ in dendritic morphology, passive membrane properties, or L4-evoked inhibitory conductance. Thus multiple gradients of physiological properties exist across L2/3 pyramidal cells, with excitatory synaptic input strength best predicting overall spiking responsiveness during network recruitment.

Volitional modulation of optically recorded calcium signals during neuroprosthetic learning.

Brain-machine interfaces are not only promising for neurological applications, but also powerful for investigating neuronal ensemble dynamics during learning. We trained mice to operantly control an auditory cursor using spike-related calcium signals recorded with two-photon imaging in motor and somatosensory cortex. Mice rapidly learned to modulate activity in layer 2/3 neurons, evident both across and within sessions. Learning was accompanied by modifications of firing correlations in spatially localized networks at fine scales.