About

Professor Spencer LaVere Smith, Ph.D., is a faculty member in the Department of Electrical and Computer Engineering at the University of California, Santa Barbara, where he also serves as Chair of the Dynamical Neuroscience Graduate Program and CEO of Pacific Optica. His research integrates computation, neuroscience, and optics, focusing on developing innovative optical systems and neurotechnology to advance the understanding of neuronal activity and brain computation. His lab has pioneered next-generation multiphoton imaging techniques that enable visualization of neuronal and synaptic activity across multiple brain areas with high resolution. This work supports new neuroscience experiments by overcoming previous technical limitations in imaging, such as short working distances and immersion requirements. Additionally, Professor Smith's research explores quantitative behavior technology, employing optimized instrumentation to study psychophysical behavior in contexts involving complex visual stimuli, thereby linking cellular and population neural activity to behaviorally relevant mechanisms.

Research topics

• Computer Science
• Biology
• Neuroscience
• Artificial Intelligence
• Physics
• Biological system
• Data science
• Optics
• Psychology
• Materials science

Selected publications

• Synergy mediates long-range correlations in the visual cortex near criticality

  Frontiers in Computational Neuroscience · 2026-02-06

  articleOpen access

  Long-range correlations are a key signature of systems operating near criticality, indicating spatially-extended interactions across large distances. These extended dependencies underlie other emergent properties of critical dynamics, such as high susceptibility and multi-scale coordination. In the brain, along with other signatures of criticality, long-range correlations have been observed across various spatial scales, suggesting that the brain may operate near a critical point to optimize information processing and adaptability. However, the mechanisms underlying these long-range correlations remain poorly understood. Here, we investigate the role of synergistic interactions in mediating long-range correlations in the visual cortex of awake mice. We leverage recent advances in mesoscale two-photon calcium imaging to analyse the activity of thousands of neurons across a wide field of view, allowing us to confirm the presence of long-range correlations at the level of neuronal populations. By applying the Partial Information Decomposition (PID) framework, we decompose the correlations into synergistic and redundant information interactions. Our results reveal that the increase in long-range correlations during visual stimulation is accompanied by a significant increase in synergistic rather than redundant interactions among neurons. Furthermore, we analyse a combined network formed by the union of synergistic and redundant interaction networks, and find that both types of interactions complement each other to facilitate efficient information processing across long distances. This complementarity is further enhanced during the visual stimulation. These findings provide new insights into the computational mechanisms that give rise to long-range correlations in neural systems and highlight the importance of considering different types of information interactions in understanding correlations in the brain.

  PublisherOA PDFDOI

• Open-source modular field-programmable gate array system for two-photon mesoscope enabling multiarea, multidepth neural activity recording and lifetime imaging

  Neurophotonics · 2026-03-03

  articleOpen access

  SignificanceLarge field-of-view (FOV) two-photon microscopy enables simultaneous recording across multiple brain regions, but larger FOVs lengthen raster scans and limit temporal resolution. A modular, open-source solution that increases imaging speed and adds fluorescence-lifetime capability on standard systems would broaden access to mesoscale neural measurements.AimWe aimed to develop and validate an open-source, modular field-programmable gate array (FPGA)-based acquisition platform and a circular delay-path (CDP) module that together enable multiarea, multidepth mesoscale two-photon imaging and large-FOV two-photon fluorescence lifetime imaging (2p-FLIM) using an 80 MHz laser.ApproachWe built an FPGA system that digitizes photomultiplier signals at 3.2 GS/s and integrated it with a CDP module for a Diesel2p mesoscope. The CDP temporally multiplexes excitation for four focal planes; the FPGA demultiplexes and reconstructs images. Lifetime imaging was implemented on the same platform.ResultsThe system enabled simultaneous recording of >10,000 neurons across the bilateral dorsal cortex at up to four depths and demonstrated large-FOV 2p-FLIM. All hardware and software are open-source and compatible with existing two-photon microscopes.ConclusionsThis modular, open-source FPGA + CDP system increases throughput of large-FOV two-photon imaging and adds lifetime contrast without specialized lasers, facilitating multiscale in vivo studies and broad biomedical applications.

  PublisherDOI

• Reviewer #1 (Public review): Mesoscale functional architecture in medial posterior parietal cortex

  2026-02-26

  peer-reviewOpen accessSenior author

  The posterior parietal cortex (PPC) in mice has various functions including multisensory integration–, vision-guided behaviors–, working memory–, and posture control,. However, an integrated understanding of these functions and their cortical localizations in and around the PPC and higher visual areas (HVAs) has not been completely elucidated. Here we simultaneously imaged the activity of thousands of neurons within a 3 x 3 mm2 field-of-view, including eight cortical areas around the PPC, during behavior with a two-photon mesoscope. Mice performed both a vision-guided task and a choice history-dependent task, and the imaging results revealed distinct, localized, behavior-related functions of two medial PPC areas. Neurons in the anteromedial (AM) HVA responded to both vision and choice information, and thus AM is a locus of association between these channels. By contrast, the anterior (A) HVA stores choice history with sequential dynamics and represents posture. Mesoscale correlation analysis on the intertrial variability of neuronal activity demonstrated that neurons in AM exhibited diverse, area-dependent interactions, while neurons in area A shared fluctuations with the primary somatosensory area. Pairwise interareal interactions among neurons were precisely predicted by the anatomical input correlations, with the exception of some global interactions. Thus, the medial PPC has two distinct modules, areas AM and A, with each having distinctive modes of cortical communication. These medial PPC modules can serve separate higher-order functions: area AM for multisensory and cognitive integration with locally processed signals and area A for transmission of information including posture, movement, and working memory.

  PublisherDOI

• Ecological Visual Processing in the Mouse

  Annual Review of Neuroscience · 2026-03-20

  articleSenior author

  Visual systems evolved to extract behaviorally relevant information while animals move through and interact with their world. Such ecological vision differs fundamentally from standard laboratory paradigms in many key aspects, making this a much harder problem for the brain to solve, and for the neuroscientist to study. However, emerging technologies and experimental approaches have enabled investigation of visual computations under these ecological conditions. These approaches are particularly powerful in the mouse, combining well-developed genetic tools, high-throughput recordings, and quantifiable ethological tasks. Here we review computations that are engaged in ecological contexts, including active sensing, motion processing, scene analysis, distance estimation, and spatial perception. We delineate experimental approaches that engage these computations and synthesize current understanding of their neural implementations based on mouse research. These studies reveal how ecological vision engages distinct processing strategies and novel neural circuitry, while highlighting the vast territory that remains unexplored in understanding real-world visual computation.

  PublisherDOI

• Author response: Mesoscale functional architecture in medial posterior parietal cortex

  2026-02-26

  peer-reviewOpen accessSenior author

  The posterior parietal cortex (PPC) in mice has various functions including multisensory integration–, vision-guided behaviors–, working memory–, and posture control,. However, an integrated understanding of these functions and their cortical localizations in and around the PPC and higher visual areas (HVAs) has not been completely elucidated. Here we simultaneously imaged the activity of thousands of neurons within a 3 x 3 mm2 field-of-view, including eight cortical areas around the PPC, during behavior with a two-photon mesoscope. Mice performed both a vision-guided task and a choice history-dependent task, and the imaging results revealed distinct, localized, behavior-related functions of two medial PPC areas. Neurons in the anteromedial (AM) HVA responded to both vision and choice information, and thus AM is a locus of association between these channels. By contrast, the anterior (A) HVA stores choice history with sequential dynamics and represents posture. Mesoscale correlation analysis on the intertrial variability of neuronal activity demonstrated that neurons in AM exhibited diverse, area-dependent interactions, while neurons in area A shared fluctuations with the primary somatosensory area. Pairwise interareal interactions among neurons were precisely predicted by the anatomical input correlations, with the exception of some global interactions. Thus, the medial PPC has two distinct modules, areas AM and A, with each having distinctive modes of cortical communication. These medial PPC modules can serve separate higher-order functions: area AM for multisensory and cognitive integration with locally processed signals and area A for transmission of information including posture, movement, and working memory.

  PublisherDOI

• Mesoscale functional architecture in medial posterior parietal cortex

  eLife · 2026-02-26

  articleOpen accessSenior author

  The posterior parietal cortex (PPC) in mice has various functions including multisensory integration1–3, vision-guided behaviors4–6, working memory7–13, and posture control14,15. However, an integrated understanding of these functions and their cortical localizations in and around the PPC and higher visual areas (HVAs) has not been completely elucidated. Here we simultaneously imaged the activity of thousands of neurons within a 3 x 3 mm2 field-of-view, including eight cortical areas around the PPC, during behavior with a two-photon mesoscope16. Mice performed both a vision-guided task and a choice history-dependent task, and the imaging results revealed distinct, localized, behavior-related functions of two medial PPC areas. Neurons in the anteromedial (AM) HVA responded to both vision and choice information, and thus AM is a locus of association between these channels. By contrast, the anterior (A) HVA stores choice history with sequential dynamics and represents posture. Mesoscale correlation analysis on the intertrial variability of neuronal activity demonstrated that neurons in AM exhibited diverse, area-dependent interactions, while neurons in area A shared fluctuations with the primary somatosensory area. Pairwise interareal interactions among neurons were precisely predicted by the anatomical input correlations, with the exception of some global interactions. Thus, the medial PPC has two distinct modules, areas AM and A, with each having distinctive modes of cortical communication. These medial PPC modules can serve separate higher-order functions: area AM for multisensory and cognitive integration with locally processed signals and area A for transmission of information including posture, movement, and working memory.

  PublisherDOI

• Reviewer #2 (Public review): Mesoscale functional architecture in medial posterior parietal cortex

  2026-02-26

  peer-reviewOpen accessSenior author

  The posterior parietal cortex (PPC) in mice has various functions including multisensory integration–, vision-guided behaviors–, working memory–, and posture control,. However, an integrated understanding of these functions and their cortical localizations in and around the PPC and higher visual areas (HVAs) has not been completely elucidated. Here we simultaneously imaged the activity of thousands of neurons within a 3 x 3 mm2 field-of-view, including eight cortical areas around the PPC, during behavior with a two-photon mesoscope. Mice performed both a vision-guided task and a choice history-dependent task, and the imaging results revealed distinct, localized, behavior-related functions of two medial PPC areas. Neurons in the anteromedial (AM) HVA responded to both vision and choice information, and thus AM is a locus of association between these channels. By contrast, the anterior (A) HVA stores choice history with sequential dynamics and represents posture. Mesoscale correlation analysis on the intertrial variability of neuronal activity demonstrated that neurons in AM exhibited diverse, area-dependent interactions, while neurons in area A shared fluctuations with the primary somatosensory area. Pairwise interareal interactions among neurons were precisely predicted by the anatomical input correlations, with the exception of some global interactions. Thus, the medial PPC has two distinct modules, areas AM and A, with each having distinctive modes of cortical communication. These medial PPC modules can serve separate higher-order functions: area AM for multisensory and cognitive integration with locally processed signals and area A for transmission of information including posture, movement, and working memory.

  PublisherDOI

• Reviewer #3 (Public review): Mesoscale functional architecture in medial posterior parietal cortex

  2026-02-26

  peer-reviewOpen accessSenior author

  The posterior parietal cortex (PPC) in mice has various functions including multisensory integration–, vision-guided behaviors–, working memory–, and posture control,. However, an integrated understanding of these functions and their cortical localizations in and around the PPC and higher visual areas (HVAs) has not been completely elucidated. Here we simultaneously imaged the activity of thousands of neurons within a 3 x 3 mm2 field-of-view, including eight cortical areas around the PPC, during behavior with a two-photon mesoscope. Mice performed both a vision-guided task and a choice history-dependent task, and the imaging results revealed distinct, localized, behavior-related functions of two medial PPC areas. Neurons in the anteromedial (AM) HVA responded to both vision and choice information, and thus AM is a locus of association between these channels. By contrast, the anterior (A) HVA stores choice history with sequential dynamics and represents posture. Mesoscale correlation analysis on the intertrial variability of neuronal activity demonstrated that neurons in AM exhibited diverse, area-dependent interactions, while neurons in area A shared fluctuations with the primary somatosensory area. Pairwise interareal interactions among neurons were precisely predicted by the anatomical input correlations, with the exception of some global interactions. Thus, the medial PPC has two distinct modules, areas AM and A, with each having distinctive modes of cortical communication. These medial PPC modules can serve separate higher-order functions: area AM for multisensory and cognitive integration with locally processed signals and area A for transmission of information including posture, movement, and working memory.

  PublisherDOI

• Open-source modular FPGA system for two-photon mesoscope enabling multi-layer, multi-depth neural activity recording and lifetime imaging

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-18 · 2 citations

  preprintOpen access

  Abstract Large field-of-view (FOV) two-photon microscopy makes it possible to record a large number of neural activities from multiple brain regions simultaneously. However, the larger the field of view, the longer it takes to scan the entire FOV. To increase imaging speed, we have developed open-source software to digitize analogue signals from a photomultiplier tube using a field-programmable gate array (FPGA) at a rate of 3.2 GS/s. By combining this with a newly developed a circular delay-path module for a custom two-photon mesoscope (Diesel2p), we succeeded in simultaneous recording of >10,000 neurons from the entire bilateral dorsal cortex at up to four depths. We also demonstrated large FOV lifetime imaging using the same system. Our modular, open-source FPGA system can be readily integrated into any type of two-photon microscope and will accelerate the biomedical application of multi-scale two-photon imaging in a wide range of pathophysiological investigations.

  PublisherOA PDFDOI

• Mesoscale functional architecture in medial posterior parietal cortex

  eLife · 2025-02-07 · 2 citations

  preprintOpen accessSenior author

  Summary The posterior parietal cortex (PPC) in mice has various functions including multisensory integration1–3, vision-guided behaviors4–6, working memory7–13, and posture control14,15. However, an integrated understanding of these functions and their cortical localizations in and around the PPC and higher visual areas (HVAs), has not been completely elucidated. Here we simultaneously imaged the activity of thousands of neurons within a 3 x 3 mm2 field-of-view, including eight cortical areas around the PPC, during behavior with a two-photon mesoscope16. Mice performed both a vision-guided task and a choice history-dependent task, and the imaging results revealed distinct, localized, behavior-related functions of two medial PPC areas. Neurons in the anteromedial (AM) HVA responded to both vision and choice information, and thus AM is a locus of association between these channels. By contrast, the anterior (A) HVA stores choice history with sequential dynamics and represents posture. Mesoscale correlation analysis on the intertrial variability of neuronal activity demonstrated that neurons in area A shared fluctuations with the primary somatosensory area, while neurons in AM exhibited diverse, area-dependent interactions. Pairwise interarea interactions among neurons were precisely predicted by the anatomical input correlations, with the exception of some global interactions. Thus, the medial PPC has two distinct modules, areas A and AM, which each have distinctive modes of cortical communication. These medial PPC modules can serve separate higher-order functions: area A for transmission of information including posture, movement, and working memory; and area AM for multisensory and cognitive integration with locally processed signals.

  PublisherDOI

Recent grants

• NeuroNex Technology Hub: Nemonic: Next generation multiphoton neuroimaging consortium

  NSF · $7.4M · 2018–2023

• Development and function of higher visual areas in mice

  NIH · $1.7M · 2015–2021

• BRAIN EAGER: Panoramic, dynamic, multi-region two-photon microscopy for systems neuroscience

  NSF · $300k · 2014–2016

• NIH Grant F32EY016633

  NIH · $78k · 2008

• Modulation of dendritic spiking in vivo

  NIH · $2.0M · 2018–2022

Frequent coauthors

• Yiyi Yu

  University of California, Santa Barbara

  30 shared

• Ikuko T. Smith

  University of California, Santa Barbara

  26 shared

• Jeffrey N. Stirman

  University of North Carolina at Chapel Hill

  22 shared

• Riichiro Hira

  14 shared

• Che‐Hang Yu

  University of California, Santa Barbara

  14 shared

• Christopher R. Dorsett

  University of California, Santa Barbara

  11 shared

• Benjamin D. Philpot

  University of North Carolina at Chapel Hill

  8 shared

• L. B. TOWNSEND

  University of North Carolina at Chapel Hill

  8 shared

Labs

• SLABPI

  Computation, Optics, Neuroscience, and Neuroengineering. Research and Engineering Laboratory at UCSB.