Publications - Salk Institute for Biological Studies

2026 PUBLICATIONS

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Sejnowski, T.J. Dynamical mechanisms for coordinating long-term working memory based on the precision of spike-timing in cortical neurons. (2026) Biol Cybern. 120(3-4). DOI: 10.1007/s00422-026-01039-3

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In the last century, most sensorimotor studies of cortical neurons relied on average firing rates. Rate coding is efficient for fast sensorimotor processing that occurs within a few seconds. Much less is known about the neural mechanisms underlying long-term working memory with a time scale of hours (Ericsson and Kintsch in Psychol Rev 102(2):211, 1995). Cognitive states may not have sensory or motor correlates. For example, you can sit in a quiet room making plan without moving or sensory processing. You can also make plans while out walking. This suggests that the neural substrate for cognitive states neither depends on nor interferes with ongoing sensorimotor brain activity. In this perspective, I make the case for a possible second tier of neural activity that coexists with the well-established sensorimotor tier. The prominent physiological feature of the second tier is coordinated spike timing activity. The interplay of data supporting this hypothesis involves three puzzling yet highly intriguing experimental observations, without any obvious indication that they might actually represent different aspects of a single functional organization. First, consider the precision of spiking in individual neurons. The discovery of millisecond-precision spike initiation in cortical neurons was unexpected (Mainen and Sejnowski in Science 268:1503-1506, 1995). Even more striking was the precision of spiking in vivo, in response to rapidly fluctuating sensory inputs. Second, high temporal resolution can also mediate spike timing-dependent plasticity (STDP) by controlling the relative timing of presynaptic and postsynaptic spikes at the millisecond scale. Third, we observe waves across many frequency bands traveling across the cortex. Strikingly, their timing is highly precise. Gamma waves, for example, which are triggered by attention, can plausibly trigger STDP that lasts for hours in cortical neurons. This temporary cortical network, ostensibly a second tier of functionality, rides astride the long-term sensorimotor network and could support cognitive processing and long-term working memory.

Hughes, J.B., Sandholm, A., Croll, D., Senchyna, F., Schneider, K., Butterfield, R., McHugh, T.L.M., Brown, I., Deguchi, H., Hilsabeck, T.A.U., Mak, S., Wilson, K.A., Davtyan, H., Blurton-Jones, M., Herdy, J., Higuchi-Sanabria, R., Gage, F.H., Furman, D., Ellerby, L.M., Desprez, P.Y., Campisi, J. DNA damage drives a unique, Alzheimer's disease-relevant senescent state in neurons. (2026) bioRxiv. DOI: 10.64898/2026.04.02.716205

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Da Silva, I.I.N., Ramirez, D., Parylak, S.L., Wallace, L.A., Tucker, J.K., Erberich, J.M., Katariya, R., McDonald, A.H., Gallina, I.S., Tucker, A.L., Burgado, J., Jaeger, B.N., Barron, J.J., Pratt, J.M., Pena, M., Racha, V., Lim, C.K., Fernandes, S., Benassi, S., Randolph-Moore, L., Vadodaria, K.C., Marchetto, M.C., Allen, N.J., Gage, F.H. CK2 inhibition suppresses glial inflammation in models of neuroinflammation and neurodegeneration. (2026) Nature Communications. DOI: 10.1038/s41467-026-71736-x

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Barykina, N.V., Carey, E.M., Oliinyk, O.S., Mendonça-Gomes, J.M., de Oliveira, S., Nimmerjahn, A., Verkhusha, V.V. Synthetic multicolor antigen-stabilizable nanobody platform for intersectional labeling and functional imaging. (2026) Nature Methods. DOI: 10.1038/s41592-026-03056-3

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Lucciola, R., Herdy, J.R., Vajaphattana, Y., Karbacher, L., Sabedot, T.S., Cuoco, M.S., Traxler, L., Kang, A., Reynolds, M., Jones, J.R., Schafer, S.T., Mertens, J., Gage, F.H. RUNX1 and YY1 modulate neuronal fate and energy metabolism in Alzheimer's disease. (2026) bioRxiv. DOI: 10.64898/2026.04.13.716801

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Doludda, B., Barde, W., D'Egidio, F., Fitzsimons, C.P., Frisén, J., Gage, F.H., Jessberger, S., Lazarov, O., Lie, D.C., Lucassen, P.J., de Lucia, C., Salta, E., Song, H., Song, J., Thuret, S., Toda, T., Kempermann, G. Neurogénesis adulta: Nuevas neuronas, nuevas oportunidades. (2026) Células Madre. 33(3):382-392. DOI: 10.1016/j.stem.2026.01.014

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Bright, M., Mi, X., Duarte, D., Carey, E., Lyu, B., Wang, Y., Nimmerjahn, A., Yu, G. AQuA2-Cloud: a web platform for fluorescence bioimaging activity analysis. (2026) bioRxiv. DOI: 10.64898/2026.03.06.709938

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Duff, M.K., Li, M.J., Nimmerjahn, A. Astrocyte Regulation of Spinal Circuit Function. (2026) J Neurochem. 170(2):e70366. DOI: 10.1111/jnc.70366

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The spinal cord stands as a crucial nexus in the central nervous system (CNS), integrating and modulating signals that ultimately shape our everyday interactions with the world. Its gray matter is arranged into discrete laminae spanning the dorsal-ventral axis that encompass circuit-specific modalities. Concurrently, extensive interconnected interneuron networks within and between these laminae confer remarkable flexibility in the behavioral outputs for a given input. The flexibility of spinal cord information processing in light of its organized architecture makes it a particularly intriguing region to explore the neuronal computations underlying behaviors, particularly as they relate to neurological dysfunction. At the same time, astrocytes engage in highly dynamic interactions with underlying neuronal circuitries, suggesting they may add another dimension to spinal cord information processing. Technical limitations specific to the spinal cord have long limited our ability to interrogate the relationship between astrocyte-neuron interactions and ongoing spinal cord function. In this review, we highlight emerging insights-particularly those from recent in vivo studies-that illustrate astrocytes actively shape spinal cord behavioral outputs in both health and disease. We briefly review the spinal cord's neuronal organization to provide a structural foundation for assessing the relative spatial relationship between astrocyte and neuron activity as it relates to different spinal cord outputs. Within this architectural framework, we review growing evidence that spinal cord astrocytes respond to activity associated with spinal cord function and, in turn, modulate underlying neuronal circuits to alter future behavioral outputs. Moreover, we propose an overall conceptual framework for understanding circuit-specific spinal cord modulations through the lens of astrocyte-neuron interactions and underscore how it can be leveraged to uncover novel ways of targeting spinal cord disease states. Finally, we put forth key outstanding questions related to this conceptual framework and emphasize the technological advances that will facilitate future studies addressing them.

Tsuda, B., Pate, S.C., Tye, K.M., Siegelmann, H.T., Sejnowski, T.J. Neuromodulators Generate Multiple Context-Relevant Behaviors in Recurrent Neural Networks. (2026) Computación neuronal.:1-36 DOI: 10.1162/NECO.a.1489

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Keller, T.A., Muller, L., Sejnowski, T.J., Welling, M. A Spatiotemporal Perspective on Dynamical Computation in Neural Information Processing Systems. (2026) ArXiv.

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Argueti-Ostrovsky, S., Lim, S.M., Arogundade, O.A., Diaz-Garcia, S., Yunisova, G., Meng, A., Hermann, A., Ong, K., Eremenko, E., Bravo-Hernandez, M., Driscoll, S.P., Lee, C.Z., Jiang, X., Stavsky, A., Barel, S., Shani, T., Kahn, J., Pfaff, S.L., Monsonego, A., Marsala, M., Ravits, J., Lagier-Tourenne, C., Israelson, A. Impaired nucleocytoplasmic transport in SOD1-mediated ALS. (2026) Mol Neurodegener. DOI: 10.1186/s13024-026-00930-8

Wagner, M., Chen, Y., Karuvally, A., Cameron, M., Sejnowski, T.J. Balancing Stability and Flow in Hippocampal Networks via Inductive Bias and Learned Symmetry Breaking. (2026) bioRxiv. DOI: 10.64898/2026.02.06.704443

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Hur, M., Bartol, T.M., Rangamani, P., Sejnowski, T.J., Mjolsness, E. Synaptic spine head morphodynamics from graph grammar rules for actin dynamics. (2026) bioRxiv. DOI: 10.1101/2025.04.18.649558

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Centro Waitt de Biofotónica Avanzada

Instituto Salk de Estudios Biológicos - Center Avanzado de Biofotónica Waitt - Investigación

2026 PUBLICATIONS

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