Honors & Awards

  • K99 Pathway to Independence Award, NIH NINDS (2020-2025)
  • AP Giannini Fellowship, AP Giannini Foundation (2018-2020)
  • Stanford Dean's Fellowship Award, Stanford School of Medicine (2017-2018)
  • Ruth L. Kirschstein National Research Service Award (Awarded, declined), NIH NINDS (2018)
  • Kavli Award for Distinguished Research (for PhD thesis), Columbia University (2016)
  • GRFP Fellow, National Science Foundation (2011-2014)
  • IGERT Fellow, National Science Foundation (2009-2010)
  • Departmental Honors (Cognitive Science), University of California San Diego (2007)
  • Chancellor's Undergraduate Research Scholarship, University of California San Diego (2007)
  • Provost's Honors, University of California San Diego (2005-2007)

Boards, Advisory Committees, Professional Organizations

  • Co-Founder and Advisor, CTRL-Labs (2015 - Present)

Professional Education

  • Bachelor of Science, University of California San Diego (2008)
  • Doctor of Philosophy, Columbia University (2015)

Stanford Advisors

All Publications

  • Cortical Observation by Synchronous Multifocal Optical Sampling Reveals Widespread Population Encoding of Actions. Neuron Kauvar, I. V., Machado, T. A., Yuen, E. n., Kochalka, J. n., Choi, M. n., Allen, W. E., Wetzstein, G. n., Deisseroth, K. n. 2020


    To advance the measurement of distributed neuronal population representations of targeted motor actions on single trials, we developed an optical method (COSMOS) for tracking neural activity in a largely uncharacterized spatiotemporal regime. COSMOS allowed simultaneous recording of neural dynamics at ∼30 Hz from over a thousand near-cellular resolution neuronal sources spread across the entire dorsal neocortex of awake, behaving mice during a three-option lick-to-target task. We identified spatially distributed neuronal population representations spanning the dorsal cortex that precisely encoded ongoing motor actions on single trials. Neuronal correlations measured at video rate using unaveraged, whole-session data had localized spatial structure, whereas trial-averaged data exhibited widespread correlations. Separable modes of neural activity encoded history-guided motor plans, with similar population dynamics in individual areas throughout cortex. These initial experiments illustrate how COSMOS enables investigation of large-scale cortical dynamics and that information about motor actions is widely shared between areas, potentially underlying distributed computations.

    View details for DOI 10.1016/j.neuron.2020.04.023

    View details for PubMedID 32433908

  • Cortical layer-specific critical dynamics triggering perception. Science (New York, N.Y.) Marshel, J. H., Kim, Y. S., Machado, T. A., Quirin, S. n., Benson, B. n., Kadmon, J. n., Raja, C. n., Chibukhchyan, A. n., Ramakrishnan, C. n., Inoue, M. n., Shane, J. C., McKnight, D. J., Yoshizawa, S. n., Kato, H. E., Ganguli, S. n., Deisseroth, K. n. 2019


    Perceptual experiences may arise from neuronal activity patterns in mammalian neocortex. We probed mouse neocortex during visual discrimination using a red-shifted channelrhodopsin (ChRmine, discovered through structure-guided genome mining) alongside multiplexed multiphoton-holography (MultiSLM), achieving control of individually-specified neurons spanning large cortical volumes with millisecond precision. Stimulating a critical number of stimulus-orientation-selective neurons drove widespread recruitment of functionally-related neurons, a process enhanced by (but not requiring) orientation-discrimination task learning. Optogenetic targeting of orientation-selective ensembles elicited correct behavioral discrimination. Cortical layer specific-dynamics were apparent, as emergent neuronal activity asymmetrically propagated from layer-2/3 to layer-5, and smaller layer-5 ensembles were as effective as larger layer-2/3 ensembles in eliciting orientation discrimination behavior. Population dynamics emerging after optogenetic stimulation both correctly predicted behavior and resembled natural neural representations of visual stimuli.

    View details for DOI 10.1126/science.aaw5202

    View details for PubMedID 31320556

  • Primacy of Flexor Locomotor Pattern Revealed by Ancestral Reversion of Motor Neuron Identity CELL Machado, T. A., Pnevmatikakis, E., Paninski, L., Jessell, T. M., Miri, A. 2015; 162 (2): 338-350


    Spinal circuits can generate locomotor output in the absence of sensory or descending input, but the principles of locomotor circuit organization remain unclear. We sought insight into these principles by considering the elaboration of locomotor circuits across evolution. The identity of limb-innervating motor neurons was reverted to a state resembling that of motor neurons that direct undulatory swimming in primitive aquatic vertebrates, permitting assessment of the role of motor neuron identity in determining locomotor pattern. Two-photon imaging was coupled with spike inference to measure locomotor firing in hundreds of motor neurons in isolated mouse spinal cords. In wild-type preparations, we observed sequential recruitment of motor neurons innervating flexor muscles controlling progressively more distal joints. Strikingly, after reversion of motor neuron identity, virtually all firing patterns became distinctly flexor like. Our findings show that motor neuron identity directs locomotor circuit wiring and indicate the evolutionary primacy of flexor pattern generation.

    View details for DOI 10.1016/j.cell.2015.06.036

    View details for Web of Science ID 000358087700014

    View details for PubMedID 26186188

    View details for PubMedCentralID PMC4540486

  • Community-based benchmarking improves spike rate inference from two-photon calcium imaging data PLOS COMPUTATIONAL BIOLOGY Berens, P., Freeman, J., Deneux, T., Chenkov, N., McColgan, T., Speiser, A., Macke, J. H., Turaga, S. C., Mineault, P., Rupprecht, P., Gerhard, S., Friedrich, R. W., Friedrich, J., Paninski, L., Pachitariu, M., Harris, K. D., Bolte, B., Machado, T. A., Ringach, D., Stone, J., Rogerson, L. E., Sofroniew, N. J., Reimer, J., Froudarakis, E., Euler, T., Roson, M., Theis, L., Tolias, A. S., Bethge, M. 2018; 14 (5): e1006157


    In recent years, two-photon calcium imaging has become a standard tool to probe the function of neural circuits and to study computations in neuronal populations. However, the acquired signal is only an indirect measurement of neural activity due to the comparatively slow dynamics of fluorescent calcium indicators. Different algorithms for estimating spike rates from noisy calcium measurements have been proposed in the past, but it is an open question how far performance can be improved. Here, we report the results of the spikefinder challenge, launched to catalyze the development of new spike rate inference algorithms through crowd-sourcing. We present ten of the submitted algorithms which show improved performance compared to previously evaluated methods. Interestingly, the top-performing algorithms are based on a wide range of principles from deep neural networks to generative models, yet provide highly correlated estimates of the neural activity. The competition shows that benchmark challenges can drive algorithmic developments in neuroscience.

    View details for DOI 10.1371/journal.pcbi.1006157

    View details for Web of Science ID 000434012100031

    View details for PubMedID 29782491

    View details for PubMedCentralID PMC5997358

  • Robust and scalable Bayesian analysis of spatial neural tuning function data The Annals of Applied Statistics Rad, K. R., Machado, T. A., Paninski, L. 2017; 11 (2): 598-637

    View details for DOI 10.1214/16-AOAS996

  • Spinal Inhibitory Interneuron Diversity Delineates Variant Motor Microcircuits CELL Bikoff, J. B., Gabitto, M. I., Rivard, A. F., Drobac, E., Machado, T. A., Miri, A., Brenner-Morton, S., Famojure, E., Diaz, C., Alvarez, F. J., Mentis, G. Z., Jessell, T. M. 2016; 165 (1): 207-219


    Animals generate movement by engaging spinal circuits that direct precise sequences of muscle contraction, but the identity and organizational logic of local interneurons that lie at the core of these circuits remain unresolved. Here, we show that V1 interneurons, a major inhibitory population that controls motor output, fractionate into highly diverse subsets on the basis of the expression of 19 transcription factors. Transcriptionally defined V1 subsets exhibit distinct physiological signatures and highly structured spatial distributions with mediolateral and dorsoventral positional biases. These positional distinctions constrain patterns of input from sensory and motor neurons and, as such, suggest that interneuron position is a determinant of microcircuit organization. Moreover, V1 diversity indicates that different inhibitory microcircuits exist for motor pools controlling hip, ankle, and foot muscles, revealing a variable circuit architecture for interneurons that control limb movement.

    View details for DOI 10.1016/j.cell.2016.01.027

    View details for Web of Science ID 000372785600021

    View details for PubMedID 26949184

    View details for PubMedCentralID PMC4808435

  • Simultaneous Denoising, Deconvolution, and Demixing of Calcium Imaging Data NEURON Pnevmatikakis, E. A., Soudry, D., Gao, Y., Machado, T. A., Merel, J., Pfau, D., Reardon, T., Mu, Y., Lacefield, C., Yang, W., Ahrens, M., Bruno, R., Jessell, T. M., Peterka, D. S., Yuste, R., Paninski, L. 2016; 89 (2): 285-299


    We present a modular approach for analyzing calcium imaging recordings of large neuronal ensembles. Our goal is to simultaneously identify the locations of the neurons, demix spatially overlapping components, and denoise and deconvolve the spiking activity from the slow dynamics of the calcium indicator. Our approach relies on a constrained nonnegative matrix factorization that expresses the spatiotemporal fluorescence activity as the product of a spatial matrix that encodes the spatial footprint of each neuron in the optical field and a temporal matrix that characterizes the calcium concentration of each neuron over time. This framework is combined with a novel constrained deconvolution approach that extracts estimates of neural activity from fluorescence traces, to create a spatiotemporal processing algorithm that requires minimal parameter tuning. We demonstrate the general applicability of our method by applying it to in vitro and in vivo multi-neuronal imaging data, whole-brain light-sheet imaging data, and dendritic imaging data.

    View details for DOI 10.1016/j.neuron.2015.11.037

    View details for Web of Science ID 000373564700007

    View details for PubMedID 26774160

    View details for PubMedCentralID PMC4881387

  • Clustered factor analysis of multineuronal spike data Advances in Neural Information Processing Systems 27 (NIPS 2014) Buesing, L., Machado, T. A., Cunningham, J. P., Paninski, L. 2014; 1
  • Efficient Coding of Spatial Information in the Primate Retina JOURNAL OF NEUROSCIENCE Doi, E., Gauthier, J. L., Field, G. D., Shlens, J., Sher, A., Greschner, M., Machado, T. A., Jepson, L. H., Mathieson, K., Gunning, D. E., Litke, A. M., Paninski, L., Chichilnisky, E. J., Simoncelli, E. P. 2012; 32 (46): 16256-16264


    Sensory neurons have been hypothesized to efficiently encode signals from the natural environment subject to resource constraints. The predictions of this efficient coding hypothesis regarding the spatial filtering properties of the visual system have been found consistent with human perception, but they have not been compared directly with neural responses. Here, we analyze the information that retinal ganglion cells transmit to the brain about the spatial information in natural images subject to three resource constraints: the number of retinal ganglion cells, their total response variances, and their total synaptic strengths. We derive a model that optimizes the transmitted information and compare it directly with measurements of complete functional connectivity between cone photoreceptors and the four major types of ganglion cells in the primate retina, obtained at single-cell resolution. We find that the ganglion cell population exhibited 80% efficiency in transmitting spatial information relative to the model. Both the retina and the model exhibited high redundancy (~30%) among ganglion cells of the same cell type. A novel and unique prediction of efficient coding, the relationships between projection patterns of individual cones to all ganglion cells, was consistent with the observed projection patterns in the retina. These results indicate a high level of efficiency with near-optimal redundancy in visual signaling by the retina.

    View details for DOI 10.1523/JNEUROSCI.4036-12.2012

    View details for Web of Science ID 000311091000019

    View details for PubMedID 23152609

    View details for PubMedCentralID PMC3537829

  • Fast Nonnegative Deconvolution for Spike Train Inference From Population Calcium Imaging JOURNAL OF NEUROPHYSIOLOGY Vogelstein, J. T., Packer, A. M., Machado, T. A., Sippy, T., Babadi, B., Yuste, R., Paninski, L. 2010; 104 (6): 3691-3704


    Fluorescent calcium indicators are becoming increasingly popular as a means for observing the spiking activity of large neuronal populations. Unfortunately, extracting the spike train of each neuron from a raw fluorescence movie is a nontrivial problem. This work presents a fast nonnegative deconvolution filter to infer the approximately most likely spike train of each neuron, given the fluorescence observations. This algorithm outperforms optimal linear deconvolution (Wiener filtering) on both simulated and biological data. The performance gains come from restricting the inferred spike trains to be positive (using an interior-point method), unlike the Wiener filter. The algorithm runs in linear time, and is fast enough that even when simultaneously imaging >100 neurons, inference can be performed on the set of all observed traces faster than real time. Performing optimal spatial filtering on the images further refines the inferred spike train estimates. Importantly, all the parameters required to perform the inference can be estimated using only the fluorescence data, obviating the need to perform joint electrophysiological and imaging calibration experiments.

    View details for DOI 10.1152/jn.01073.2009

    View details for Web of Science ID 000285392700067

    View details for PubMedID 20554834

    View details for PubMedCentralID PMC3007657

  • Functional connectivity in the retina at the resolution of photoreceptors NATURE Field, G. D., Gauthier, J. L., Sher, A., Greschner, M., Machado, T. A., Jepson, L. H., Shlens, J., Gunning, D. E., Mathieson, K., Dabrowski, W., Paninski, L., Litke, A. M., Chichilnisky, E. J. 2010; 467 (7316): 673-U54


    To understand a neural circuit requires knowledge of its connectivity. Here we report measurements of functional connectivity between the input and ouput layers of the macaque retina at single-cell resolution and the implications of these for colour vision. Multi-electrode technology was used to record simultaneously from complete populations of the retinal ganglion cell types (midget, parasol and small bistratified) that transmit high-resolution visual signals to the brain. Fine-grained visual stimulation was used to identify the location, type and strength of the functional input of each cone photoreceptor to each ganglion cell. The populations of ON and OFF midget and parasol cells each sampled the complete population of long- and middle-wavelength-sensitive cones. However, only OFF midget cells frequently received strong input from short-wavelength-sensitive cones. ON and OFF midget cells showed a small non-random tendency to selectively sample from either long- or middle-wavelength-sensitive cones to a degree not explained by clumping in the cone mosaic. These measurements reveal computations in a neural circuit at the elementary resolution of individual neurons.

    View details for DOI 10.1038/nature09424

    View details for Web of Science ID 000282572500030

    View details for PubMedID 20930838

    View details for PubMedCentralID PMC2953734