Welcome to the Soltesz Lab website! Our lab is part of the Stanford School of Medicine, Department of Neurosurgery, and is led by Dr. Ivan Soltesz.
We are interested in how brain cells communicate with each other in the normal brain, and how the communication changes in epilepsy.
Postdoctoral fellows and graduate students in the lab employ closely integrated, cutting-edge experimental and computational modeling techniques to understand normal and epilepsy-related plasticity in neuronal networks. The techniques include simultaneous patch clamp recordings from rigorously identified interneurons and principal cells, in vivo recordings and functional imaging, closed-loop optogenetics, behavioral methods, and biologically highly realistic large-scale supercomputational modeling approaches.
Epilepsy study links mossy brain cells to seizures and memory loss
NIH-funded study in mice suggests loss of mossy cells plays a critical role in both
One Scientist's Quest To Vanquish Epileptic Seizures
Ivan Soltesz studies epilepsy in mice, but says children with chronic seizures are his inspiration. He's closing in on a way to quell the seizures with light — and without drugs' side effects.
02/15/2018 Anh's paper published in Science:
Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory
08/08/2017 Gergely's paper published in Cell Reports: Extended Interneuronal Network of the Dentate Gyrus
12/23/2016 Marianne's paper published in eLife: Interneuronal mechanisms of hippocampal theta oscillation in a full-scale model of the rodent CA1 circuit
05/19/2016 Soltesz Lab research mentioned in Nature News article, Light-controlled genes and neurons poised for clinical trials
05/12/2016 Ivan has been elected to the Hungarian Academy of Sciences! http://mta.hu/english/introducing-the-newly-elected-members-of-the-hungarian-academy-of-sciences-106486
04/04/2016 Ivan has been awarded computing time allocation on Blue Waters, the NSF-funded petascale computing system, for constructing full-scale computational models of the hippocampus.
I am using electrophysiological and optogenetic methods to investigate how neurons in the dentate gyrus control seizures.
I use 2-photon calcium imaging and electrophysiological methods to investigate the role of endocannabinoids in hippocampal function.
I take care of administrative duties and also help lab members with technical aspects of their research.
I am interested in studying learning and memory in epilepsy, and how optogenetic suppression of seizures can affect the cognitive deficits found in a mouse model of epilepsy.
I incorporate experimental data generated in the Soltesz lab and the labs of our collaborators to build a computational model of the hippocampus.
I am using genetics, in vitro and in vivo electrophysiology, 2-photon calcium imaging, and closed-loop optogenetics to investigate the molecular and circuit mechanisms of epilepsy.
I help lab members with technical aspects of their research.
I am working on building a computational model of the hippocampus.
I am studying the structure and function of hippocampal GABAergic circuitry using juxtacellular recordings in awake mice combined with imaging and optogenetic tools.
- Mattia Maroso (Post-doc through 2017), now Associate Editor, AAAS.
- Sanghun Lee (Post-doc through 2015), now Assistant Professor at the University of Arkansas for Medical Sciences.
- Esther Krook-Magnuson (Post-doc through 2014), now Assistant Professor at the University of Minnesota.
- Csaba Varga (Post-doc through 2014), now Assistant Professor at the University of Pecs, Hungary.
- Caren Armstrong (Doctoral student and post-doc through 2011) now a Resident in Pediatric Neurology at Johns Hopkins University.
- Soo Yeun Lee (Doctoral student through 2011) now a Postdoctoral Fellow at Department of Bioengineering, Stanford University
- Sarah Feldt (Post-doc through 2011) now Assistant Professor at the University at Buffalo, State University of New York.
- Csaba Foldy (Doctoral student and post-doc through 2010) now a Postdoctoral Fellow at Department of Molecular and Cellular Physiology, Stanford University
- Kang Chen (Post-doc through 2009) now an Associate Specialist at Department of Neuroniology and Behavior, University of California, Irvine
- Janos Szabadics (Postdoc through 2009) now a Faculty at Central Medical Research Institute, Budapest, Hungary
- Robert J. Morgan (Doctoral student through 2009) now a Resident Psychiatrist at Rochester, MN
- Julio Echegoyen (Doctoral student through 2008) now a Fellow at Shiley Eye Institute, University of California, San Diego.
- Raphael Winkels (Visiting doctoral student through 2008) now a Postdoctoral Fellow at Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University Frankfurt, Frankfurt, Germany
- Jonas Dhyrfjeld-Johnsen (Post-doc through 2007) now a Senior Project Leader in Sensorion.
- Axel Neu (Post-doc through 2007) now a Principal Investigator at Hamburg University
- Allyson Alexander (Doctoral student through 2006) now a Resident Neurosurgeon at Stanford University
- Mykola Lysetskiy (Post-doc through 2005) now at Northwestern University
- Ildiko Aradi (Post-doc through 2003) now Head of Clinical Development of Biologics at Gedeon Richter Plc., Hungary
- Viji Santhakumar (Post-doc and doctoral student through 2003) now an Assistant Professor at New Jersey Medical School
- Anna de Haas Ratzliff (Doctoral student through 2003) now an Assistant Professor at Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle
- Stephen Ross (Doctoral student through 2001) now a General Manager of Product and Marketing at Nikon Instruments USA, Inc.
- Niklas Thon (Doctoral student through 2001) (Visited from the University of Freiburg, Germany)
- Greg Hollrigel (Doctoral student through 1998) now an Attorney at Stout Uxa Buyan & Mullins LLP
- Zsolt Toth (Post-doc through 1997) now a Cardiac Surgeon at Department of Cardiac Surgery, Al-Dabbous Cardiac Center, Al-Adan Hospital
We imagine the brain as a neural forest, with the trees represented by pyramidal cells with their characteristic long apical dendrites. Located among this forest of principal cells are the diverse and heterogeneous interneurons which are comprised of many "species" of cell types. The goal of the Soltesz lab is to understand this diversity of the interneurons, to define and characterize the different cell types, determine how they interact with one another and the principal cells in the neural forest, and ultimately decipher the functional necessity for this diversity.
We are interested in an area of the brain that is critical for learning and memory called the hippocampus. Utilizing various molecular, genetic, electrophysiological, imaging, and behavioral tools we aim to decipher how interneurons modulate the flow of information through the hippocampus and how their dysfunction in neurological disorders such as epilepsy contribute to neurocognitive decline.
NIH BRAIN Initiative: Understanding the Circuitry Underlying Sharp-Wave Mediated Memory Replay
We are making the first attempt to fully understand a cognitively important event, called memory replay, in terms of the detailed properties of the brain cells involved. We use cutting-edge large-scale recording technologies to study and manipulate identified cell types, and are developing novel methods to provide needed information about the connectivity between the neurons involved. Finally, we are constructing the first full-scale computational of model of the brain area that produces the memory replay in which every cell is explicitly simulated. These powerful new approaches are likely to yield major insights into the principles by which the interactions of neurons gives rise to cognitive function, with important implications for memory disorders.
NIH and NASA: Characterizing the Effects of Medical and Space Irradiation on Neuronal Function
The future of space exploration involves human travel to, and eventually colonization of, other planets. However, before we send our brave astronauts there, it is imperative to know the effects ionizing space irradiation can have on their neuronal function. With support from NASA and in collaboration with the Limoli lab at UC Irvine, the Soltesz lab is helping characterize the effects of space irradiation on synapses, circuits, and behavior.
For those back on Earth, the Limoli and Soltesz labs, with support from NIH, are also characterizing the effects of medical doses of radiation on neuronal function.
Ultimately, we want to identify the molecular mechanisms underlying radiation-induced neurocognitive deficits for future therapeutic intervention, both here at home on Earth and millions of miles away.
Techniques We Employ
In vivo 2-photon microscopy
In vitro & In vivo Electrophysiology
Neuronal Reconstruction & Identification
Full-scale neuronal network modeling of spatial learning & memory in the hippocampus
The hippocampal circuits that store and recall spatial information are comprised of diverse cell types, each exhibiting distinct dynamics and complex patterns of synaptic connectivity. Thus, even highly specific experimental perturbations of a single component of these neuronal circuits can have counterintuitive effects on their internal dynamics and output. Computational modeling offers experimentalists a framework to integrate their knowledge, make explicit the assumptions of their conceptual models, and quantitatively predict how each element of a neuronal network is expected to respond to cell type- or projection-specific perturbations.
Our team’s approach to neural circuit modeling is unique in that experimentalists and theorists in our lab are completely integrated. This allows constant interaction between data and model to help us generate hypotheses, design experiments, and analyze and interpret our results.
We are currently developing full-scale (1:1) network models of the dentate gyrus (DG), CA3, and CA1 subregions of the hippocampus to understand the cellular, synaptic and network mechanisms for memory storage and recall, and to aide in the interpretation of physiological and behavioral experimental data. Most previous neuronal network models have focused on either large networks with greatly simplified neuronal morphologies and biophysics, or small networks with more detailed descriptions of individual cells. However, over the last decade, advances in cellular and system neuroscience have revealed that the fundamental computations performed by networks of neurons in the brain cannot be simply abstracted from the physical substrate that implements them. Rather, computation in neural circuits depends heavily on
1) compartmentalized signaling in neuronal dendrites
2) diverse neuronal cell types with distinct morphology, genetics, and function
3) short- and long-term adaptation and synaptic plasticity
4) highly non-random, cell-type specific patterns of synaptic connectivity
Fortunately, advances in parallel computing now enable us to test our understanding of the fundamental mechanisms controlling neuronal network function without having to sacrifice detail at either the microscale of neuronal biophysics or the mesoscale of connectivity between cell types and brain regions. By constructing full-scale models that maintain a 1:1 correspondence to the cell types, synaptic mechanisms, and ion channels that are studied in the lab, we can directly compare various types of experimental data to the results of simulations, from spikes recorded electrophysiologically, to intracellular voltage or calcium measured optically.
Below are resources and datasets resulting from our computational work that we have made publicly available.
CA1 Quantitative Assessment
We have quantitatively assessed the CA1 network of the rat hippocampus. Sufficient information has been published about the rat CA1 to estimate the numbers of each interneuron type, as well as the connectivity of the pyramidal cells, interneurons, and afferents. We believe these estimates provide a valuable resource for modelers, theorists, and experimentalists wishing to close the gaps in our neuroanatomical knowledge of the CA1. To refer to the resources listed on this page, please cite the associated, published quantitative assessment:
Bezaire MJ, Soltesz I. 2013. Quantitative Assessment of CA1 Local Circuits: Knowledge Base for Interneuron-Pyramidal Cell Connectivity. Hippocampus.
Spreadsheet Contains all calculations used in the assessment. Available on Google Docs
Online Database Currently in progress; contains experimental data used in assessment. Available here.
Full-scale model of the hippocampal CA1 region with spontaneous theta, gamma: full scale & network clamp (Bezaire et al 2016)
This model is a full-scale, biologically constrained rodent hippocampal CA1 network model that includes 9 cell types (pyramidal cells and 8 interneurons) with anatomically realistic numbers of each and realistic connectivity between the cells. In addition, the model cells receive afferents from artificial cells representing hippocampal CA3 and entorhinal cortical layer III. The model is fully scaleable and parallelized so that it can be run at small scale on a personal computer or large scale on a supercomputer. The model network exhibits spontaneous theta and gamma rhythms without any rhythmic input. The model network can be perturbed in a variety of ways to study the mechanisms of CA1 network dynamics.
CA1 superdeep microcircuit model
The superdeep model is associated with Lee et al., (2014). This detailed microcircuit model explores the network level effects of sublayer specific connectivity in the mouse CA1.
This detailed 50,000+ neuron model of the rat dentate gyrus is used to study network dynamics in the healthy and epileptic dentate. It was first created by Santhakumar et al., (2005), and updated in Morgan et al., (2007, 2008), Dyhrfjeld-Johnsen et al., (2007), and Schneider et al., (2012).
Special thanks to our computational resource sponsors and collaborators!
Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory.
Science 16 Feb 2018 : 787-790
Authors: Bui A, Nguyen T, Limouse C, Kim HK, Szabo GG, Felong S, Maroso M, Soltesz I
Hippocampal Dentate Mossy Cells Improve Their CV and Trk into the Limelight.
Neuron. 2017 Aug 16;95(4):732-734. doi: 10.1016/j.neuron.2017.08.005.
Authors: Milstein AD, Soltesz I.
Extended Interneuronal Network of the Dentate Gyrus.
Cell Reports, 2017 Aug 8; 20 (6): 1262-1268.
Authors: Szabo G, Du X, Oijala M, Varga C, Parent J, Soltesz I.
Involvement of fast-spiking cells in ictal sequences during spontaneous seizures in rats with chronic temporal lobe epilepsy.
Brain, 2017; 140 (9): 2355–2369.
Authors: Neumann A, Raedt R, Steenland H, Sprengers M, Bzymek K, Navratilova Z, Mesina L, Xie J, Lapointe V, Kloosterman F, Vonck K, Boon P, Soltesz I, McNaughton B, Luczak A.
Network models of epilepsy-related pathological structural and functional alterations in the dentate gyrus.
In: van Ooyen A, Butz-Ostendorf M, eds., The Rewiring Brain: A Computational Approach to Structural Plasticity in the Adult Brain. San Diego: Academic Press, 2017
Authors: Raikov I, Plitt M, Soltesz I.
Hippocampal in silico models of seizures and epilepsy.
In: Pitkänen A, Buckmaster P, Galanopoulou A, Moshé S, eds., Models of Seizures and Epilepsy, 2nd ed. Academic Press, 2017.
Authors: Raikov I, Soltesz I.
Interneuronal mechanisms of hippocampal theta oscillation in a full-scale model of the rodent CA1 circuit
Authors: Bezaire MJ, Raikov I, Burk K, Vyas D, Soltesz I.
Neurophysiology of space travel: energetic solar particles cause cell type-specific plasticity of neurotransmission.
Brain Struct Funct. 2016 Nov 30.
Authors: Lee SH, Dudok B, Parihar VK, Jung KM, Zöldi M, Kang YJ, Maroso M, Alexander AL, Nelson GA, Piomelli D, Katona I, Limoli CL, Soltesz I.
Organization and control of epileptic circuits in temporal lobe epilepsy.
Prog Brain Res. 2016;226:127-54. doi: 10.1016/bs.pbr.2016.04.007. Epub 2016 Jun 7.
Authors: Alexander A, Maroso M, Soltesz I.
Cannabinoid Control of Learning and Memory through HCN Channels.
Neuron. 2016 Feb 16. pii: S0896-6273(16)00048-9.
Authors: Maroso M, Szabo GG, Kim HK, Alexander A, Bui AD, Lee SH, Lutz B, Soltesz I.
Hippogate: a break-in from entorhinal cortex.
Nat Neurosci. 2016 Feb 15.
Authors: Alexander A, Soltesz I.
Publications in 2015
Seizing Control: From Current Treatments to Optogenetic Interventions in Epilepsy
Neuroscientist. 2015 Dec 23. pii: 1073858415619600.
Authors: Bui AD, Alexander A, Soltesz I
Target-Selectivity of Parvalbumin-Positive Interneurons in Layer II of Medial Entorhinal Cortex in Normal and Epileptic Animals
Hippocampus. 2015 Dec 13. doi: 10.1002/hipo.22559
Authors: Armstrong C, Wang J, Lee SY, Broderick J, Bezaire MJ, Lee SH, Soltesz I
Brain State Is a Major Factor in Preseizure Hippocampal Network Activity and Influences Success of Seizure Intervention
J Neurosci. 2015 Nov 25;35(47):15635-48.
Authors: Ewell LA, Liang L, Armstrong C, Soltesz I, Leutgeb S, Leutgeb JK.
Microcircuits in Epilepsy: Heterogeneity and Hub Cells in Network Synchronization.
Cold Spring Harb Perspect Med. 2015;5(11)
Authors: Bui A, Kim HK, Maroso M, Soltesz I
Pass-Through Code of Synaptic Integration.
Neuron. 2015 Sep 23;87(6):1124-6
Authors: Szabo GG, Soltesz I
A Master Plan for the Epilepsies? Toward a General Theory of Seizure Dynamics.
Epilepsy Curr. 2015 May-Jun;15(3):133-5
Authors: Raikov I, Soltesz I
Optogenetics: 10 years after ChR2 in neurons--views from the community.
Nat Neurosci. 2015 Sep;18(9):1202-12
Authors: Adamantidis A, Arber S, Bains JS, Bamberg E, Bonci A, Buzsáki G, Cardin JA, Costa RM, Dan Y, Goda Y, Graybiel AM, Häusser M, Hegemann P, Huguenard JR, Insel TR, Janak PH, Johnston D, Josselyn SA, Koch C, Kreitzer AC, Lüscher C, Malenka RC, Miesenböck G, Nagel G, Roska B, Schnitzer MJ, Shenoy KV, Soltesz I, Sternson SM, Tsien RW, Tsien RY, Turrigiano GG, Tye KM, Wilson RI
Multiple Forms of Endocannabinoid and Endovanilloid Signaling Regulate the Tonic Control of GABA Release.
J Neurosci. 2015 Jul 8;35(27):10039-57
Authors: Lee SH, Ledri M, Tóth B, Marchionni I, Henstridge CM, Dudok B, Kenesei K, Barna L, Szabó SI, Renkecz T, Oberoi M, Watanabe M, Limoli CL, Horvai G, Soltesz I, Katona I
Future of seizure prediction and intervention: closing the loop.
J Clin Neurophysiol. 2015 Jun;32(3):194-206
Authors: Nagaraj V, Lee ST, Krook-Magnuson E, Soltesz I, Benquet P, Irazoqui PP, Netoff TI
Neuroelectronics and Biooptics: Closed-Loop Technologies in Neurological Disorders.
JAMA Neurol. 2015 Jul;72(7):823-9
Authors: Krook-Magnuson E, Gelinas JN, Soltesz I, Buzsáki G
Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy.
Nat Rev Neurosci. 2015 May;16(5):264-77
Authors: Soltesz I, Alger BE, Kano M, Lee SH, Lovinger DM, Ohno-Shosaku T, Watanabe M
In vivo evaluation of the dentate gate theory in epilepsy.
J Physiol. 2015 May 15;593(10):2379-88
Authors: Krook-Magnuson E, Armstrong C, Bui A, Lew S, Oijala M, Soltesz I
Beyond the hammer and the scalpel: selective circuit control for the epilepsies.
Nat Neurosci. 2015 Mar;18(3):331-8
Authors: Krook-Magnuson E, Soltesz I
Net worth of networks: specificity in anticonvulsant action.
Epilepsy Curr. 2015 Jan-Feb;15(1):45-6. doi: 10.5698/1535-7597-15.1.45.
Authors: Schneider CJ, Soltesz I.
Proton radiation alters intrinsic and synaptic properties of CA1 pyramidal neurons of the mouse hippocampus.
Sokolova IV, Schneider CJ, Bezaire M, Soltesz I, Vlkolinsky R, Nelson GA.
Radiat Res. 2015 Feb;183(2):208-18. doi: 10.1667/RR13785.1. Epub 2015 Jan 26.
Upcoming Scientific Events
Society for Neuroscience Annual Meeting. November 11-15, 2017.
Ivan Raikov will be presenting his poster at SFN this year. Come check it out!
Soltesz Lab Retreat. November 17-19, 2017.
We will be having our annual lab retreat at the Hilton hotel at Scotts Valley, up in the beautiful Santa Cruz mountains.
NASA Human Research Program Investigators' Workshop. January 23-26, 2017.
Ivan will be presenting the findings from our NASA-sponsored research project involving the functional consequences of deep space radiation in the CNS.
Past Scientific Events
Cannabinoid Signaling in Epilepsy: Pathways to Therapy. October 9-10, 2017.
Ivan co-hosted a workshop on cannabinoid signaling in epilepsy that took place at Stanford and featured speakers from the basic, clinical, and biopharmaceutical fields.
Gordon Research Conference: Cannabinoid Function in the CNS. August 20-25, 2017.
Ivan and Barna presented at the GRC on Cannabinoid Function in the CNS which took place in Waterville Valley, NH.
Stanford Epilepsy Seminar: Liset de la Prida. July 26, 2017.
Quynh Anh hosted Liset de la Prida, Director of the Laboratory for Neural Circuits at the Cajal Institute in Madrid, Spain to present to members of the Stanford School of Medicine and trainees in the Stanford Epilepsy Training Program.