Research
The long-term mission of our research is to understand the molecular, cellular, and circuit mechanisms underlying higher order cognitive processes.
Cognitive processes of particular interest include working memory, long-term memory encoding and retrieval, attention, and decision-making.
While our projects start with a focus on basic science questions, in most cases, we will build on this foundation to determine how disease states alter neural mechanisms that underlie cognition. Ultimately, we aim to identify therapeutic strategies to alleviate disease phenotypes.
Evolutionary studies have suggested that the expanded neocortex in humans, as compared to other mammalian species, underlies our superior cognitive functions.
These cortical functions critically depend on the integration of internal states (emotion) and external information (sensory inputs). The thalamus, being a crucial region for sensory processing and multi-sensory integration with both bottom-up and top-down connectivity, is in a powerful anatomical and functional position to guide cortical processes. While past thalamic research has focused mostly on pure sensory processing (i.e., their relay role), the importance of non-relay functions has recently been emphasized but much less understood.
Using the mouse model primarily, our laboratory will identify novel cell types in the thalamus, develop molecular approaches to target individual cell types in vivo, and link these cell types to specific cognitive functions using physiological recordings together with behavioral assays.
These projects will employ single-cell RNA sequencing, brain-wide activity mapping, circuit tracing, in vivo neural activity measurements (fiber photometry, one-photon calcium imaging), CRISPR, neural manipulation approaches (chemogenetics, optogenetics), computational modeling, and human organoid models.
Projects
Thalamic cell types and circuits underlying cognition
Starting with transcriptomic approaches, we identify novel/understudied cell types in the rodent thalamus and develop genetic tools (mouse lines and/or viral constructs) for in vivo access. These cell types and their circuits will be linked to specific cognitive processes using behavioral and neural activity readouts.
Intersection of computation and neuroscience research
How can experimental systems neuroscience findings help us better understand computational functions of the brain? One way that we use our discoveries is to build synaptic plasticity frameworks and recurrent neural networks (RNN). These models allow us to probe detailed plasticity mechanisms and develop additional hypotheses for experimental studies.
Thalamic dysfunction in psychiatric and neurodegenerative disorders
Although thalamic phenotypes have been found in patients with psychiatric (autism, schizophrenia) and neurodegenerative (Parkinson’s, Alzheimer’s) disorders, their role in disease progression, as well as their potential as therapeutic targets, remain poorly understood. Using mouse models, we have a track record of studying thalamic dysfunction in disease states, which is a major research goal moving forward as well.
Developing human organoid models
While rodent studies will continue to enhance our understanding of thalamic contributions to health and disease, we aim to bridge the gap between animal and human applications. For this purpose, we are developing human organoid models that will allow us to understand cortical and thalamocortical mechanisms with more direct relevance for us. Moving forward, patient samples will be used to generate organoid models and help us search for therapeutic targets.
