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.

Lab Members

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

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