@article {48935, title = {Fully integrated silicon probes for high-density recording of neural activity.}, journal = {Nature}, volume = {551}, year = {2017}, month = {2017 Nov 08}, pages = {232-236}, abstract = {

Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca(2+) imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal-oxide-semiconductor (CMOS) processing-compatible low-impedance TiN sites that tile a single 10-mm long, 70 {\texttimes} 20-μm cross-section shank. The 6 {\texttimes} 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.

}, issn = {1476-4687}, doi = {10.1038/nature24636}, author = {Jun, James J and Steinmetz, Nicholas A and Siegle, Joshua H and Denman, Daniel J and Bauza, Marius and Barbarits, Brian and Lee, Albert K and Anastassiou, Costas A and Andrei, Alexandru and Ayd{\i}n, {\c C}a{\u g}atay and Barbic, Mladen and Blanche, Timothy J and Bonin, Vincent and Couto, Jo{\~a}o and Dutta, Barundeb and Gratiy, Sergey L and Gutnisky, Diego A and H{\"a}usser, Michael and Karsh, Bill and Ledochowitsch, Peter and Lopez, Carolina Mora and Mitelut, Catalin and Musa, Silke and Okun, Michael and Pachitariu, Marius and Putzeys, Jan and Rich, P Dylan and Rossant, Cyrille and Sun, Wei-Lung and Svoboda, Karel and Carandini, Matteo and Harris, Kenneth D and Koch, Christof and O{\textquoteright}Keefe, John and Harris, Timothy D} } @article {47974, title = {Layer 4 fast-spiking interneurons filter thalamocortical signals during active somatosensation.}, journal = {Nature Neuroscience}, volume = {19}, year = {2016}, month = {2016 Oct 17}, pages = {1647-57}, abstract = {

We rely on movement to explore the environment, for example, by palpating an object. In somatosensory cortex, activity related to movement of digits or whiskers is suppressed, which could facilitate detection of touch. Movement-related suppression is generally assumed to involve corollary discharges. Here we uncovered a thalamocortical mechanism in which cortical fast-spiking interneurons, driven by sensory input, suppress movement-related activity in layer 4 (L4) excitatory neurons. In mice locating objects with their whiskers, neurons in the ventral posteromedial nucleus (VPM) fired in response to touch and whisker movement. Cortical L4 fast-spiking interneurons inherited these responses from VPM. In contrast, L4 excitatory neurons responded mainly to touch. Optogenetic experiments revealed that fast-spiking interneurons reduced movement-related spiking in excitatory neurons, enhancing selectivity for touch-related information during active tactile sensation. These observations suggest a fundamental computation performed by the thalamocortical circuit to accentuate salient tactile information.

}, issn = {1546-1726}, doi = {10.1038/nn.4412}, author = {Yu, Jianing and Gutnisky, Diego A and Hires, S Andrew and Svoboda, Karel} } @article {46987, title = {Low-noise encoding of active touch by layer 4 in the somatosensory cortex.}, journal = {eLife}, volume = {4}, year = {2015}, month = {2015 Aug 6}, abstract = {

Cortical spike trains often appear noisy, with the timing and number of spikes varying across repetitions of stimuli. Spiking variability can arise from internal (behavioral state, unreliable neurons, or chaotic dynamics in neural circuits) and external (uncontrolled behavior or sensory stimuli) sources. The amount of irreducible internal noise in spike trains, an important constraint on models of cortical networks, has been difficult to estimate, since behavior and brain state must be precisely controlled or tracked. We recorded from excitatory barrel cortex neurons in layer 4 during active behavior, where mice control tactile input through learned whisker movements. Touch was the dominant sensorimotor feature, with \>70\% spikes occurring in millisecond timescale epochs after touch onset. The variance of touch responses was smaller than expected from Poisson processes, often reaching the theoretical minimum. Layer 4 spike trains thus reflect the millisecond-timescale structure of tactile input with little noise.

}, issn = {2050-084X}, doi = {10.7554/eLife.06619}, author = {Andrew Hires, Samuel and Gutnisky, Diego A and Yu, Jianing and O{\textquoteright}Connor, Daniel H and Svoboda, Karel} } @article {6295, title = {Organization of cortical and thalamic input to pyramidal neurons in mouse motor cortex.}, journal = {The Journal of Neuroscience}, volume = {33}, year = {2013}, month = {2013 Jan 9}, pages = {748-60}, abstract = {

Determining how long-range synaptic inputs engage pyramidal neurons in primary motor cortex (M1) is important for understanding circuit mechanisms involved in regulating movement. We used channelrhodopsin-2-assisted circuit mapping to characterize the long-range excitatory synaptic connections made by multiple cortical and thalamic areas onto pyramidal neurons in mouse vibrissal motor cortex (vM1). Each projection innervated vM1 pyramidal neurons with a unique laminar profile. Collectively, the profiles for different sources of input partially overlapped and spanned all cortical layers. Specifically, orbital cortex (OC) inputs primarily targeted neurons in L6. Secondary motor cortex (M2) inputs excited neurons mainly in L5B, including pyramidal tract neurons. In contrast, thalamocortical inputs from anterior motor-related thalamic regions, including VA/VL (ventral anterior thalamic nucleus/ventrolateral thalamic nucleus), targeted neurons in L2/3 through L5B, but avoided L6. Inputs from posterior sensory-related thalamic areas, including POm (posterior thalamic nuclear group), targeted neurons only in the upper layers (L2/3 and L5A), similar to inputs from somatosensory (barrel) cortex. Our results show that long-range excitatory inputs target vM1 pyramidal neurons in a layer-specific manner. Inputs from sensory-related cortical and thalamic areas preferentially target the upper-layer pyramidal neurons in vM1. In contrast, inputs from OC and M2, areas associated with volitional and cognitive aspects of movements, bypass local circuitry and have direct monosynaptic access to neurons projecting to brainstem and thalamus.

}, keywords = {Animals, Cerebral Cortex, Data Interpretation, Efferent Pathways, Electric Stimulation, Electrophysiological Phenomena, Female, Inbred C57BL, Male, Mice, Motor Cortex, Neurons, Patch-Clamp Techniques, Pons, Pyramidal Tracts, Statistical, Thalamus}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.4338-12.2013}, author = {Hooks, Bryan M and Mao, Tianyi and Gutnisky, Diego A and Yamawaki, Naoki and Svoboda, Karel and Shepherd, Gordon M G} } @article {5162, title = {Activity in motor-sensory projections reveals distributed coding in somatosensation.}, journal = {Nature}, volume = {489}, year = {2012}, month = {2012 Sep 13}, pages = {299-303}, abstract = {

Cortical-feedback projections to primary sensory areas terminate most heavily in layer 1 (L1) of the neocortex, where they make synapses with tuft dendrites of pyramidal neurons. L1 input is thought to provide {\textquoteleft}contextual{\textquoteright} information, but the signals transmitted by L1 feedback remain uncharacterized. In the rodent somatosensory system, the spatially diffuse feedback projection from vibrissal motor cortex (vM1) to vibrissal somatosensory cortex (vS1, also known as the barrel cortex) may allow whisker touch to be interpreted in the context of whisker position to compute object location. When mice palpate objects with their whiskers to localize object features, whisker touch excites vS1 and later vM1 in a somatotopic manner. Here we use axonal calcium imaging to track activity in vM1{\textendash}\>vS1 afferents in L1 of the barrel cortex while mice performed whisker-dependent object localization. Spatially intermingled individual axons represent whisker movements, touch and other behavioural features. In a subpopulation of axons, activity depends on object location and persists for seconds after touch. Neurons in the barrel cortex thus have information to integrate movements and touches of multiple whiskers over time, key components of object identification and navigation by active touch.

}, issn = {1476-4687}, doi = {10.1038/nature11321}, author = {Petreanu, Leopoldo and Gutnisky, Diego A and Huber, Daniel and Xu, Ning-long and O{\textquoteright}Connor, Dan H and Tian, Lin and Looger, Loren and Svoboda, Karel} }