About

David Kleinfeld is a Professor in the Physics Department at UC San Diego. His laboratory focuses on active sensation, microcirculation, neurotechnology, and techniques related to neuroscience research. As the Principal Investigator, he leads efforts in understanding neural mechanisms and developing innovative neurotechnological tools. His work involves collaboration with project scientists, postdoctoral fellows, graduate students, and data analysts, contributing to advancing knowledge in neurophysics and related fields.

Research topics

• Neuroscience
• Biology
• Pathology
• Medicine
• Chemistry
• Materials science
• Biophysics
• Internal medicine
• Biochemistry
• Nanotechnology
• Psychology

Selected publications

• Touch sensation: Convergent mechanical sensitivity between elephant and rat whiskers

  Current Biology · 2026-05-01

  articleOpen access

  New work reveals that elephant whiskers, also known as vibrissae, have elliptical, stiff, and porous bases along with soft tips. This contrasts with the uniform, highly tapered nature of rodent vibrissae. Nonetheless, these differences in design lead to similar mechanical sensitivity to vibrissa-based touch.

  PublisherDOI

• Microvascular architecture and physiological fluctuations constrain the control of cerebral microcirculation - figure data

  Zenodo (CERN European Organization for Nuclear Research) · 2026-01-15

  datasetOpen accessSenior author
  PublisherDOI

• The neurovascular impulse response function differentially reflects intrinsic neuromodulation across cortical regions

  Nature Neuroscience · 2026-03-26 · 1 citations

  article
  PublisherDOI

• Fast and accessible morphology-free functional fluorescence imaging analysis

  PLoS Computational Biology · 2026-03-12

  articleOpen access

  Optical calcium imaging is a powerful tool for recording neural activity across a wide range of spatial scales, from dendrites and spines to whole-brain imaging through two-photon and widefield microscopy. Traditional methods for analyzing functional calcium imaging data rely heavily on spatial features, such as the compact shapes of somas, to extract regions of interest and their associated temporal traces. This spatial dependency can introduce biases in time trace estimation and limit the applicability of these methods across different neuronal morphologies and imaging scales. To address these limitations, the Graph Filtered Temporal Dictionary Learning (GraFT) uses a graph-based approach to identify neural components based on shared temporal activity rather than spatial proximity, enhancing generalizability across diverse datasets. Here we present significant advancements to the GraFT algorithm, including the integration of a more efficient solver for the L1 least absolute shrinkage and selection operator (LASSO) problem and the application of compressive sensing techniques to reduce computational complexity. By employing random projections to reduce data dimensionality, we achieve substantial speedups while maintaining analytical accuracy. These advancements significantly accelerate the GraFT algorithm, making it more scalable for larger and more complex datasets. Moreover, to increase accessibility, we developed a graphical user interface to facilitate running and analyzing the outputs of GraFT. Finally, we demonstrate the utility of GraFT to imaging data beyond meso-scale imaging, including vascular and axonal imaging.

  PublisherDOI

• A hypoxia-sensitive medullary nucleus modulates cerebral blood flow via a disynaptic pathway to cortex

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-21

  articleOpen accessSenior authorCorresponding

  Abstract The RVLM (rostral ventral lateral medulla) region of the brainstem is implicated as a controller of both systemic and cerebral blood flow (CBF). Past studies leave open the question of how the RVLM stabilizes CBF in awake animals. Here, we focus on CBF regulation by the adenergic subpopulation of RVLM neurons (RVLM Dβh ). Hypoxic challenge increases the variability of the activity of RVLM Dβh neurons along with increased CBF. Experimental photoactivation of RVLM Dβh neurons leads to rapid vasodilation of pial arterioles across the cortical mantle and increased CBF, which is only then followed by an increase in cortical activity. No significant changes in systemic physiology are observed. Virus tracing establishes disynaptic pathways from the RVLM to neocortex with predominant relays involving the lateral hypothalamus and the zona incerta subthalamic nuclei. Chemogenetic inhibition of those nuclei led to a 70 % reduction in the ability of photoactivated RVLM Dβh neurons to induce cortical vasodilation and increase CBF. In toto, these findings reveal a major RVLM subcortical pathway to drive transcortical increases in CBF and represent an adaptive mechanism to inform the cerebral vasculature about environmental shifts in pO 2 .

  PublisherDOI

• Microvascular architecture and physiological fluctuations constrain the control of cerebral microcirculation

  Proceedings of the National Academy of Sciences · 2026-01-15 · 2 citations

  articleOpen accessSenior author

  Brain vasculature is a multiscale network that actively regulates cerebral blood flow to maintain homeostasis. A systematic understanding of how this network enables robust and precise flow control has been hindered by the lack of understanding of flow in networks, as opposed to single vessels. To address this gap at the conceptual level, we theoretically studied nonperturbative, network-level flow responses to hydrodynamic conductance changes in individual vessels. We show vasodilation can either increase or decrease flow in the neighboring branches, yet selectively positioning the "controller" in the inflow branch of diverging nodes guarantees downstream increases in flow, regardless of surrounding network topology. Moreover, the effect of an individual vasodilation is small, so coordinated vasodilation is essential for effective regulation. To validate and refine our theoretical analysis, we developed a computational framework to analyze individual blood cell motion captured by confocal light field microscopy. This approach enabled tracking over one million cell detections across a network of more than 3,000 interconnected branches, with 2 µm spatial and 14 ms temporal resolution. Network-based analysis uncovered significant flow fluctuations, exhibiting long-range anticorrelation in spatially separated segments. The prevalence of diverging nodes within three branches of penetrating arterioles suggests that ensheathing pericytes are optimally positioned for fine-scale flow regulation. Finally, we quantified a phase separation of blood serum and cells at diverging nodes. This revealed a stochastic partition ratio with a nonlinear dependence on local hemodynamics. Collectively, our work highlights principles of organization for the control of blood flow among the seemingly random connectivity of brain microvessels.

  PublisherOA PDFDOI

• Microvascular architecture and physiological fluctuations constrain the control of cerebral microcirculation - figure data

  Open MIND · 2026-01-15

  datasetSenior author
  DOI

• Defects, parcellation, and renormalized negative diffusivities in non-homogeneous oscillatory media

  ArXiv.org · 2025-02-13

  preprintOpen access

  Spatial non-homogeneities can synchronize clusters of spatially-extended oscillators in different frequency plateaus. Motivated by physiological rhythms, we fully characterize the phase diagram of a Ginzburg-Landau (GL) model with a gradient of frequencies. For large gradients and diffusion, the rest state is stable, and the linear spectrum around it maps onto the non-Hermitian Bloch-Torrey equation. When complex pairs of eigenvalues turn unstable, precursors of plateaus grow, separated by defects where the GL amplitude vanishes. Nonlinear effects either saturate the amplitude of plateaus or lead to a phase-locked state, with saddle-node bifurcations separating the two regimes. In the region of plateaus, we trace the formation of defects to a non-linear renormalization of the diffusivity, and determine the scaling of their number and length vs dynamical parameters.

  PublisherOA PDFDOI

• Glutamate indicators with increased sensitivity and tailored deactivation rates

  Research Square · 2025-04-08

  preprintOpen access
  PublisherOA PDFDOI

• A brainstem map of orofacial rhythms

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-27 · 10 citations

  preprintOpen access

  Rhythmic orofacial movements, such as eating, drinking, or vocalization, are controlled by distinct premotor oscillator networks in the brainstem. Orofacial movements must be coordinated with rhythmic breathing to avoid aspiration and because they share muscles. Understanding how brainstem circuits coordinate rhythmic motor programs requires neurophysiological measurements in behaving animals. We used Neuropixels probe recordings to map brainstem neural activity related to breathing, licking, and swallowing in mice drinking water. Breathing and licking rhythms were tightly coordinated and phase-locked, whereas intermittent swallowing paused breathing and licking. Multiple clusters of neurons, each recruited during different orofacial rhythms, delineated a lingual premotor network in the intermediate nucleus of the reticular formation (IRN). Local optogenetic perturbation experiments identified a region in the IRN where constant stimulation can drive sustained rhythmic licking, consistent with a central pattern generator for licking. Stimulation to artificially induce licking showed that coupled brainstem oscillators autonomously coordinated licking and breathing. The brainstem oscillators were further patterned by descending inputs at moments of licking initiation. Our results reveal the logic governing interactions of orofacial rhythms during behavior and outline their neural circuit dynamics, providing a model for dissecting multi-oscillator systems controlling rhythmic motor programs.

  PublisherDOI

Recent grants

• Direct wavefront sensing and adaptive optics to enable two-photon imaging axons and spines throughout all of cortex

  NIH · $1.8M · 2019–2026

• MRI: Development of a Pulsed Laser Source for Deep in Vivo Imaging, a Synergy of Physics and Brain Science

  NSF · $790k · 2015–2019

• NIH Grant R21MH108503

  NIH · $362k · 2019

• Project 1

  NIH · $26.9M · 2021–2026

• NIH Grant R01MH059867

  NIH · $1.3M · 2005

Frequent coauthors

• Philbert S. Tsai

  University of California, San Diego

  60 shared

• Beth Friedman

  39 shared

• Fan Wang

  Shanghai Hospital Development Center

  34 shared

• Martin Deschênes

  33 shared

• Patrick D. Lyden

  Keck Hospital of USC

  31 shared

• Andy Y. Shih

  30 shared

• Nozomi Nishimura

  Cornell University

  29 shared

• Chris B. Schaffer

  Cornell University

  26 shared

Labs

• David Kleinfeld LaboratoryPI

  Investigates how the vibrissa sensorimotor system of rodents extracts a stable world view through its actively moving sensors, the nature of binding orofacial actions into behavior, the biophysics of blood flow and patterned neurovascular dynamics at the level of single vessels in the brain, aspects of brain vasculature dysfunction, the nature of dopaminergic neuromodulatory dynamics in cortex, and new technologies for neuroscience.

Awards & honors

• David and Lucile Packard Foundation Interdisciplinary Scienc…
• NIH Directors Pioneer Award
• NINDS Research Program Award
• Dr. George Feher Experimental Biophysics Endowed Chair