About

Emre Aksay, Ph.D., is an Associate Professor of Physiology and Biophysics and an Associate Professor of Computational Neuroscience in the Institute for Computational Biomedicine at Weill Cornell Medicine. His research focuses on understanding the molecular, cellular, and circuit mechanisms that give rise to the rich neural dynamics observed in the brain. His work explores neural dynamics, which are critical for motor and cognitive behaviors, by working at the interface between physics and biology. His approach combines molecular-genetic manipulations, electrophysiology, multi-photon imaging, connectomics, statistical and machine learning, computational modeling, and control theory to yield insights into neuronal computations and how neurons interact to generate global brain functions. His research aims to not only advance basic science but also outline therapeutic strategies for disorders of neural dynamics.

Research topics

• Neuroscience
• Computer science
• Biology
• Psychology
• Physics

Selected publications

• Lyapunov theory demonstrating a fundamental limit on the speed of systems consolidation

  Physical Review Research · 2025-05-21 · 1 citations

  articleOpen access

  The nervous system reorganizes memories from an early site to a late site, a commonly observed feature of learning and memory systems known as systems consolidation. Previous work has suggested learning rules by which consolidation may occur. Here, we provide conditions under which such rules are guaranteed to lead to stable convergence of learning and consolidation. We use the theory of Lyapunov functions, which enforces stability by requiring learning rules to decrease an energy-like (Lyapunov) function. We present the theory in the context of a simple circuit architecture motivated by classic models of cerebellum-mediated learning and consolidation. Stability is only guaranteed if the learning rate in the late stage is not faster than the learning rate in the early stage. Further, the slower the learning rate at the late stage, the larger the perturbation the system can tolerate with a guarantee of stability. We provide intuition for this result by mapping a simple example consolidation model to a damped driven oscillator system and showing that the ratio of early- to late-stage learning rates in the consolidation model can be directly identified with the oscillator's damping ratio. We then apply the theory to modeling the tuning by the cerebellum of a well-characterized analog short-term memory system, the oculomotor neural integrator, and find similar stability conditions. This work suggests the power of the Lyapunov approach to provide constraints on nervous system function.

  PublisherOA PDFDOI

• Predicting modular functions and neural coding of behavior from a synaptic wiring diagram

  Nature Neuroscience · 2024-11-22 · 25 citations

  articleOpen access

  A long-standing goal in neuroscience is to understand how a circuit’s form influences its function. Here, we reconstruct and analyze a synaptic wiring diagram of the larval zebrafish brainstem to predict key functional properties and validate them through comparison with physiological data. We identify modules of strongly connected neurons that turn out to be specialized for different behavioral functions, the control of eye and body movements. The eye movement module is further organized into two three-block cycles that support the positive feedback long hypothesized to underlie low-dimensional attractor dynamics in oculomotor control. We construct a neural network model based directly on the reconstructed wiring diagram that makes predictions for the cellular-resolution coding of eye position and neural dynamics. These predictions are verified statistically with calcium imaging-based neural activity recordings. This work demonstrates how connectome-based brain modeling can reveal previously unknown anatomical structure in a neural circuit and provide insights linking network form to function. The authors determine the synaptic wiring diagram of a vertebrate circuit and reveal behaviorally associated modules. A model based on this connectome predicts neural coding and dynamics that are verified with calcium imaging data.

  PublisherDOI

• Cyclic structure with cellular precision in a vertebrate sensorimotor neural circuit

  Current Biology · 2023-05-25 · 12 citations

  articleOpen access

  Neuronal wiring diagrams reconstructed by electron microscopy1Wanner A.A. Friedrich R.W. Whitening of odor representations by the wiring diagram of the olfactory bulb.Nat. Neurosci. 2020; 23: 433-442Crossref PubMed Scopus (32) Google Scholar,2Witvliet D. Mulcahy B. Mitchell J.K. Meirovitch Y. Berger D.R. Wu Y. Liu Y. Koh W.X. Parvathala R. Holmyard D. et al.Connectomes across development reveal principles of brain maturation.Nature. 2021; 596: 257-261Crossref PubMed Scopus (83) Google Scholar,3Scheffer L.K. Xu C.S. Januszewski M. Lu Z. Takemura S.Y. Hayworth K.J. Huang G.B. Shinomiya K. Maitlin-Shepard J. Berg S. et al.A connectome and analysis of the adult Drosophila central brain.eLife. 2020; 9e57443https://doi.org/10.7554/eLife.57443Crossref Google Scholar,4Alexander Bae J. Baptiste M. Bodor A.L. Brittain D. Buchanan J. Bumbarger D.J. Castro M.A. Celii B. Cobos E. et al.MICrONS ConsortiumFunctional connectomics spanning multiple areas of mouse visual cortex.2021https://doi.org/10.1101/2021.07.28.454025Crossref Google Scholar,5Shapson-Coe A. Januszewski M. Berger D.R. Pope A. A connectomic study of a petascale fragment of human cerebral cortex.2021https://doi.org/10.1101/2021.05.29.446289Crossref Google Scholar pose new questions about the organization of nervous systems following the time-honored tradition of cross-species comparisons.6Bullock T. Horridge G.A. Structure and Function in the Nervous Systems of Invertebrates. Stony Brook University, 1965Google Scholar,7Nieuwenhuys R. ten Donkelaar H.J. Nicholson C. The Central Nervous System of Vertebrates: With Posters. Springer Science & Business Media, 1998Crossref Google Scholar The C. elegans connectome has been conceptualized as a sensorimotor circuit that is approximately feedforward,8Durbin R.M. Studies on the Development and Organisation of the Nervous System of Caenorhabditis elegans. University of Cambridge, 1987Google Scholar,9Varshney L.R. Chen B.L. Paniagua E. Hall D.H. Chklovskii D.B. Structural properties of the Caenorhabditis elegans neuronal network.PLoS Comput. Biol. 2011; 7e1001066Crossref PubMed Scopus (552) Google Scholar,10Jarrell T.A. Wang Y. Bloniarz A.E. Brittin C.A. Xu M. Thomson J.N. Albertson D.G. Hall D.H. Emmons S.W. The connectome of a decision-making neural network.Science. 2012; 337: 437-444Crossref PubMed Scopus (297) Google Scholar,11Cook S.J. Jarrell T.A. Brittin C.A. Wang Y. Bloniarz A.E. Yakovlev M.A. Nguyen K.C.Q. Tang L.T.-H. Bayer E.A. Duerr J.S. et al.Whole-animal connectomes of both Caenorhabditis elegans sexes.Nature. 2019; 571: 63-71Crossref PubMed Scopus (286) Google Scholar starting from sensory neurons proceeding to interneurons and ending with motor neurons. Overrepresentation of a 3-cell motif often known as the “feedforward loop” has provided further evidence for feedforwardness.10Jarrell T.A. Wang Y. Bloniarz A.E. Brittin C.A. Xu M. Thomson J.N. Albertson D.G. Hall D.H. Emmons S.W. The connectome of a decision-making neural network.Science. 2012; 337: 437-444Crossref PubMed Scopus (297) Google Scholar,12Reigl M. Alon U. Chklovskii D.B. Search for computational modules in the C. elegans brain.BMC Biol. 2004; 2: 25Crossref PubMed Scopus (82) Google Scholar Here, we contrast with another sensorimotor wiring diagram that was recently reconstructed from a larval zebrafish brainstem.13Vishwanathan A. Ramirez A.D. Wu J. Sood A. Yang R. Kemnitz N. Ih D. Turner N. Lee K. Tartavull I. et al.Predicting modular functions and neural coding of behavior from a synaptic wiring diagram.2021https://doi.org/10.1101/2020.10.28.359620Crossref Google Scholar We show that the 3-cycle, another 3-cell motif, is highly overrepresented in the oculomotor module of this wiring diagram. This is a first for any neuronal wiring diagram reconstructed by electron microscopy, whether invertebrate12Reigl M. Alon U. Chklovskii D.B. Search for computational modules in the C. elegans brain.BMC Biol. 2004; 2: 25Crossref PubMed Scopus (82) Google Scholar,14Milo R. Shen-Orr S. Itzkovitz S. Kashtan N. Chklovskii D. Alon U. Network motifs: simple building blocks of complex networks.Science. 2002; 298: 824-827Crossref PubMed Scopus (5185) Google Scholar or mammalian.15Song S. Sjöström P.J. Reigl M. Nelson S. Chklovskii D.B. Highly nonrandom features of synaptic connectivity in local cortical circuits.PLoS Biol. 2005; 3e68PubMed Google Scholar,16Perin R. Berger T.K. Markram H. A synaptic organizing principle for cortical neuronal groups.Proc. Natl. Acad. Sci. USA. 2011; 108: 5419-5424Crossref PubMed Scopus (441) Google Scholar,17Turner N.L. Macrina T. Bae J.A. Yang R. Wilson A.M. Schneider-Mizell C. Lee K. Lu R. Wu J. Bodor A.L. et al.Reconstruction of neocortex: organelles, compartments, cells, circuits, and activity.Cell. 2022; 185: 1082-1100.e24Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar The 3-cycle of cells is “aligned” with a 3-cycle of neuronal groups in a stochastic block model (SBM)18Lee C. Wilkinson D.J. A review of stochastic block models and extensions for graph clustering.Appl. Netw. Sci. 2019; 4122https://doi.org/10.1007/s41109-019-0232-2Crossref Scopus (62) Google Scholar of the oculomotor module. However, the cellular cycles exhibit more specificity than can be explained by the group cycles—recurrence to the same neuron is surprisingly common. Cyclic structure could be relevant for theories of oculomotor function that depend on recurrent connectivity. The cyclic structure coexists with the classic vestibulo-ocular reflex arc for horizontal eye movements,19Szentagothai J. The elementary vestibulo-ocular reflex arc.J. Neurophysiol. 1950; 13: 395-407Crossref PubMed Scopus (192) Google Scholar and could be relevant for recurrent network models of temporal integration by the oculomotor system.20Seung H.S. How the brain keeps the eyes still.Proc. Natl. Acad. Sci. USA. 1996; 93: 13339-13344Crossref PubMed Scopus (361) Google Scholar,21Fisher D. Olasagasti I. Tank D.W. Aksay E.R. Goldman M.S. A modeling framework for deriving the structural and functional architecture of a short-term memory microcircuit.Neuron. 2013; 79: 987-1000Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar

  PublisherOA PDFDOI

• Oculomotor plant and neural dynamics suggest gaze control requires integration on distributed timescales

  The Journal of Physiology · 2022-07-05 · 10 citations

  articleOpen access

  A fundamental principle of biological motor control is that the neural commands driving movement must conform to the response properties of the motor plants they control. In the oculomotor system, characterizations of oculomotor plant dynamics traditionally supported models in which the plant responds to neural drive to extraocular muscles on exclusively short, subsecond timescales. These models predict that the stabilization of gaze during fixations between saccades requires neural drive that approximates eye position on longer timescales and is generated through the temporal integration of brief eye velocity-encoding signals that cause saccades. However, recent measurements of oculomotor plant behaviour have revealed responses on longer timescales. Furthermore, measurements of firing patterns in the oculomotor integrator have revealed a more complex encoding of eye movement dynamics. Yet, the link between these observations has remained unclear. Here we use measurements from the larval zebrafish to link dynamics in the oculomotor plant to dynamics in the neural integrator. The oculomotor plant in both anaesthetized and awake larval zebrafish was characterized by a broad distribution of response timescales, including those much longer than 1 s. Analysis of the firing patterns of oculomotor integrator neurons, which exhibited a broadly distributed range of decay time constants, demonstrates the sufficiency of this activity for stabilizing gaze given an oculomotor plant with distributed response timescales. This work suggests that leaky integration on multiple, distributed timescales by the oculomotor integrator reflects an inverse model for generating oculomotor commands, and that multi-timescale dynamics may be a general feature of motor circuitry. KEY POINTS: Recent observations of oculomotor plant response properties and neural activity across the oculomotor system have called into question classical formulations of both the oculomotor plant and the oculomotor integrator. Here we use measurements from new and published experiments in the larval zebrafish together with modelling to reconcile recent oculomotor plant observations with oculomotor integrator function. We developed computational techniques to characterize oculomotor plant responses over several seconds in awake animals, demonstrating that long timescale responses seen in anaesthetized animals extend to the awake state. Analysis of firing patterns of oculomotor integrator neurons demonstrates the sufficiency of this activity for stabilizing gaze given an oculomotor plant with multiple, distributed response timescales. Our results support a formulation of gaze stabilization by the oculomotor system in which commands for stabilizing gaze are generated through integration on multiple, distributed timescales.

  PublisherOA PDFDOI

• Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model

  Brain · 2022-02-21 · 24 citations

  articleOpen accessSenior author

  Seizures are thought to arise from an imbalance of excitatory and inhibitory neuronal activity. While most classical studies suggest excessive excitatory neural activity plays a generative role, some recent findings challenge this view and instead argue that excessive activity in inhibitory neurons initiates seizures. We investigated this question of imbalance in a zebrafish seizure model with two-photon imaging of excitatory and inhibitory neuronal activity throughout the brain using a nuclear-localized calcium sensor. We found that seizures consistently initiated in circumscribed zones of the midbrain before propagating to other brain regions. Excitatory neurons were both more prevalent and more likely to be recruited than inhibitory neurons in initiation as compared with propagation zones. These findings support a mechanistic picture whereby seizures initiate in a region of hyperexcitation, then propagate more broadly once inhibitory restraint in the surround is overcome.

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• Zebrafish 2-photon imaging data during seizures; Original data

  Zenodo (CERN European Organization for Nuclear Research) · 2022-02-25

  datasetOpen accessSenior author

  This is imaging data in .tiff format from the publication "Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model"

  PublisherDOI

• Zebrafish 2-photon imaging data during seizures; Original data

  Zenodo (CERN European Organization for Nuclear Research) · 2022-02-25

  datasetOpen accessSenior author

  This is imaging data in .tiff format from the publication "Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model"

  PublisherDOI

• Ramp-to-threshold dynamics in a hindbrain population controls the timing of spontaneous saccades

  Nature Communications · 2021-07-06 · 23 citations

  articleOpen accessSenior author

  Organisms have the capacity to make decisions based solely on internal drives. However, it is unclear how neural circuits form decisions in the absence of sensory stimuli. Here we provide a comprehensive map of the activity patterns underlying the generation of saccades made in the absence of visual stimuli. We perform calcium imaging in the larval zebrafish to discover a range of responses surrounding spontaneous saccades, from cells that display tonic discharge only during fixations to neurons whose activity rises in advance of saccades by multiple seconds. When we lesion cells in these populations we find that ablation of neurons with pre-saccadic rise delays saccade initiation. We analyze spontaneous saccade initiation using a ramp-to-threshold model and are able to predict the times of upcoming saccades using pre-saccadic activity. These findings suggest that ramping of neuronal activity to a bound is a critical component of self-initiated saccadic movements.

  PublisherOA PDFDOI

• Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model

  bioRxiv (Cold Spring Harbor Laboratory) · 2021-03-30 · 4 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Seizures are thought to arise from an imbalance of excitatory and inhibitory neuronal activity. While most classical studies suggest excessive excitatory neural activity plays a generative role, some recent findings challenge this view and instead argue that excessive activity in inhibitory neurons initiates seizures. We investigated this question of imbalance in a zebrafish seizure model with multi-regional two-photon imaging of excitatory and inhibitory neuronal activity using a nuclear-localized calcium sensor. We found that seizures consistently initiated in circumscribed zones of the midbrain before propagating to other brain regions. Excitatory neurons were both more prevalent and more likely to be recruited than inhibitory neurons in initiation as compared with propagation zones. These findings support a mechanistic picture whereby seizures initiate in a region of hyper-excitation, then propagate more broadly once inhibitory restraint in the surround is overcome. Teaser We uncover the roles of excitation and inhibition during seizures, thus opening a path to more targeted therapy of epilepsy.

  PublisherOA PDFDOI

• Spontaneous-SR-Data

  Figshare · 2021-01-01

  datasetOpen accessSenior author

  Calcium and eye movement traces that support the findings in Ramirez, A.D &amp; Aksay E.A. <i>Ramp-to-threshold dynamics in a hindbrain population controls the timing of spontaneous saccades. </i>Nature Communications (2021).<i> </i>In this paper we show that a group of hindbrain neurons whose neuronal activity is predictive of upcoming saccades under a ramp-to-threshold model are necessary for natural saccade patterning. <br>

  PublisherDOI

Recent grants

• CRCNS: Collaborative Research: The Role of Dendritic Processing in Persistent Neural Activity

  NSF · $395k · 2012–2015

• Circuit Mechanisms Underlying Learned Changes in Persistent Neural Activity

  NIH · $4.1M · 2018–2024

• NIH Grant R01EY021581

  NIH · $2.8M · 2018

• Circuit Mechanisms Underlying Persistent Activity in a Neural Integrator

  NIH · $5.7M · 2016–2027

Frequent coauthors

• David W. Tank

  Princeton University

  53 shared

• H. Sebastian Seung

  Princeton University

  53 shared

• R. Baker

  46 shared

• Guy Major

  42 shared

• Brett D. Mensh

  Howard Hughes Medical Institute

  35 shared

• Theodore H. Schwartz

  24 shared

• Alexandro D. Ramirez

  Cornell University

  24 shared

• Hongtao Ma

  Cornell University

  24 shared