News

December 18, 2019

Behavioral Experiments

A major impediment to progress towards reproducible, rigorous preclinical research in epilepsy is that current experimental approaches often require prohibitively time and labor-intensive 24/7 video-EEG monitoring and inherently subjective scoring of seizures by human observers. In collaboration with the Datta lab at Harvard, who showed that complex animal behaviors are structured in stereotyped modules (“syllables”) at sub-second timescales arranged according to specific rules (“grammar”), we are developing a technique employing video imaging with a 3D camera and artificial intelligence (AI)-assisted video analysis to assess epileptic behavior in an automated and unbiased manner.

Lab Members

Instructor

Tilo Gschwind

Instructor

Tilo Gschwind

Focusing on hippocampal network reorganization in temporal lobe epilepsy while tackling inherent problems of decade-old technology to advance epilepsy research, his project in the Soltesz lab provides an optimal opportunity to contribute to the interdisciplinary discourse between the fields of neuroscience and AI.

We use high-density silicon probes in the hippocampus and related circuits to record from single neurons and monitor the local field potential dynamics with high spatiotemporal resolution. When combined with optogenetics, we can “tag” neurons to achieve cell-type specific recordings as mice navigate a cue-rich treadmill while head-fixed or during restraint-free behavior. Optogenetics also enables us to study how specific cells within and outside of the hippocampus control important LFP dynamics, including theta and sharp-wave ripples. We use a variety of electrode layouts, including Neuropixel probes, to cover a range of research questions.

Lab Members

Postdoctoral Researcher

Ernie Hwaun

Instructor

Tilo Gschwind

Postdoctoral Researcher

Ernie Hwaun

Ernie completed his PhD in Neuroscience from the University of Texas at Austin. He is interested in how neurons connect with each other to support cognitive functions such as memory. To tackle this problem, Ernie has been using in vivo extracellular recording techniques to obtain neuronal activity while animals perform a memory task. Besides research, Ernie enjoys playing basketball with friends and reading manga.

Instructor

Tilo Gschwind

Focusing on hippocampal network reorganization in temporal lobe epilepsy while tackling inherent problems of decade-old technology to advance epilepsy research, his project in the Soltesz lab provides an optimal opportunity to contribute to the interdisciplinary discourse between the fields of neuroscience and AI.

December 18, 2019

Closed-Loop Optogenetics

Optogenetics is a control technology that allows the fast, selective excitation or inhibition of specific neurons with light by expressing light-sensitive proteins (opsins) in particular cell types, enabling causal control of neuronal activity in behaving animals. We have developed a closed-loop, real-time, on-demand system to utilize optogenetics to provide effective seizure control in experimental models of temporal lobe epilepsy (TLE) (Krook-Magnuson et al., 2013) in a spatial, temporal, cell-type and direction of modulation-(excitation or inhibition) selective manner. Importantly, closed-loop optogenetic intervention (COI) was capable not only of curtailing electrographic seizures, but also of significantly decreasing the number of behavioral seizures. COI has proven to be a powerful new tool to understand epileptic circuits, and our lab has used it to directly test the role of the cerebellum as a distant site for seizure control in TLE (Krook-Magnuson et al., 2014) and the role of mossy cells in epilepsy (Bui et al., 2018). One of the most attractive features of COI is that the intervention is highly selective, occurring only when needed (at the time of seizures) and where it is needed, causing selective disruption of seizures while only minimally interfering with ongoing computations necessary for normal brain function. We have recently shown that prolonged application of COI can ameliorate cognitive deficits in TLE (Kim et al., 2019), providing evidence that this technology can improve both seizure burden and the associated comorbidities of epilepsy. Continuing work in the Soltesz lab is focused on utilizing COI as well as incorporating recently developed molecular tools to use with the system to identify and understand epileptic circuits both within and outside of the hippocampus. Ultimately our work aims to provide critical insight into potential targets and avenues for intervention in the treatment of epilepsy.

Lab Members

Instructor

Tilo Gschwind

Instructor

Tilo Gschwind

Focusing on hippocampal network reorganization in temporal lobe epilepsy while tackling inherent problems of decade-old technology to advance epilepsy research, his project in the Soltesz lab provides an optimal opportunity to contribute to the interdisciplinary discourse between the fields of neuroscience and AI.

To monitor the activity of specific cells during unrestricted behavior, we use open-source head-mounted miniscopes developed at UCLA (miniscope.org) to measure calcium activity. The main advantage of this approach over head-fixed 2-photon imaging is the ability to perform a broader range of behavioral tasks including artificial intelligence-based behavioral analysis. Combining these cell type-specific recordings with unbiased sub-second behavioral analysis using AI facilitates the characterization of the cellular underpinnings of behavior at a resolution not possible with conventional approaches.

Calcium Imaging from the Anterior Cingulate Cortex during exploration.

Lab Members

No members found
December 18, 2019

In-vivo Calcium Imaging

We’re using 2-photon microscopy to record neuronal activity with single-cell resolution in the hippocampus of awake, behaving mice. Taking advantage of cell type-specific viral targeting of various biosensors, our goal is to better understand how distinct populations of excitatory and inhibitory neurons are recruited during network oscillations in the healthy brain, and during pathological activity such as seizures in the epileptic brain.

Lab Members

Research Scientist

Gergely Szabo

Research Scientist

Gergely Szabo

Gergely is a Basic Life Research Scientist whose main focus is studying the structure and function of hippocampal inhibitory circuitry and its involvement in learning and memory, utilizing techniques such as electrophysiology, optogenetics, and imaging. Gergely received his MS in Biology from Eotvos Lorand University in Hungary and his Ph.D. in Neuroscience from Semmelweis University in Hungary, after which he joined the Soltesz Lab as a postdoctoral fellow.

December 18, 2019

Computational Modeling

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. In the Soltesz lab we build computational models in close collaboration with experimentalists, both in the lab, across Stanford, and at other institutions through a multi-site NIH BRAIN Initiative collaboration. Our large-scale network models of the hippocampus are continuously refined to incorporate newly obtained experimental constraints, and numerical simulations are carried out to test hypotheses, compare candidate biophysical and network mechanisms for memory storage and recall, and aide in the interpretation of physiological and behavioral experimental data. The ultimate goal of these efforts is to obtain a deep conceptual understanding of the cellular and network mechanisms that mediate “memory replay” events called sharp-wave ripples by simulating a large-scale model of the hippocampus that reproduces for the observed firing properties of all cell types during sharp-waves.

Lab Members

Research Engineer

Ivan Raikov

Postdoctoral Researcher

Alexandra Chatzikalymiou

Research Engineer

Ivan Raikov

I hold undergraduate and master’s degree in Computer Science from the Georgia Institute of Technology, and a PhD in Biomedical Sciences from the University of Antwerp. I am studying information processing in the hippocampus by means of highly detailed and realistic computational simulation of neuronal networks at 1:1 scale.  More broadly, I am interested in solving the enormous neuroinformatics challenges of computational neuroscience by developing sophisticated computational frameworks capable of expressing, organizing and managing the different types of data and algorithms associated with computational models of neural networks.

Postdoctoral Researcher

Alexandra Chatzikalymiou

Alexandra Chatzikalymniou holds a bachelor’s and a master’s degree in Chemical Engineering from the University of Patras, Greece, and a PhD in Neuroscience and Physiology from the University of Toronto. In her PhD, Alexandra focused on the modelling of theta rhythms using both phenomenological and biophysical models of the rodent hippocampus. As part of her modelling work, she used and analysed state-of-the-art biologically detailed models of the rodent CA1 developed by the Soltesz lab, to understand elements of theta rhythm generation. Alexandra is interested in place cell formation during navigation, and ripple related mechanisms of memory recall and consolidation.

Sandra is an experienced Research Laboratory Services Manager with a demonstrated history of working in the higher education industry for more than 5 years. Skilled in Molecular Biology, Cell Culture, Life Sciences, Microscopy as well as cell biology techniques that utilize laser-based technology to simultaneous multi-parametric analyze physical and chemical characteristics of tissues or cells. She is a strong research professional with a Bachelor of Science (B.Sc.) focused in Nutritional Science from University Hohenheim and a Business Administration background for more than 9 years. She has been working the last 5 years in the Genetics Department at Stanford and is now excited about her new role within the Soltesz Lab.