About the Lab
Our research focuses on brain states and multimodal integration across corticothalamic circuits. Information processing in the brain varies between brain states like sleep and wakefulness, and also more subtly between attention and inattention. When we are driving a car for example, and our attention shifts from the scene in front of us to the song on the radio, the processing of auditory and visual information can change dramatically without any anatomical rewiring of circuits in the brain. We study the mechanisms underlying the differential gating and routing of information in multiple sensory areas during these brain state changes. To address this difficult problem we record and manipulate activity in awake mice using cutting-edge techniques like targeted in vivo whole-cell patching, advanced multiphoton calcium imaging, optogenetics, and viral techniques.
Multiphoton Calcium and Voltage Imaging
With Andreas Tolias Lab, we have access to a unique range of multiphoton imaging capabilities. A 2P-RAM mesoscope (Sofroniew et al. 2016) provides sub-cellular resolution across large (5mm) fields of view. A three-photon microscope (Ouzounov et al. 2017) allows us to do functional imaging across the full thickness of mouse cortex. An Acousto-Optical Deflector (AOD) microscope (Reddy et al. 2015) enables kilohertz sampling of small populations of cells, which is ideal for a new generation of two-photon-accessible, genetically-encoded voltage indicators.
Functional Specialization of Cortical Interneurons
Using techniques like two-photon-guided in vivo whole cell patching, we can examine the functional properties of specific interneuron classes. Patching allows us to record from inside the cell to see the subthreshold inputs that are integrated to produce the cell’s spiking output in the behaving animal. Our goal is to understand the functional roles of specific interneuron classes in the cortical circuit.
Circuit Mechanisms Underlying Brain State Fluctuations in Mice
We were the first to show that the mouse pupil closely tracks brain state even in the absence of overt behaviors like running and whisking (Reimer et al, 2014). We found that during periods of pupil dilation, neural activity has many similar features to attention in humans and other primates. In collaboration with Matt McGinley (also at Baylor College of Medicine), we showed that the pupil-indexed state change corresponds with changes in the cortical release of acetylcholine and neuroepinephrine (Reimer et al, 2016). By tracking the pupil and using all the amazing recording techniques available in the mouse model, we hope to study the mechanisms that allow animals to be more or less engaged with the world around them.
Large-Scale Functional Connectomics of Visual Cortex (MICrONS)
As part of the IARPA-funded MICrONS project, our team will soon be analyzing combined functional and structural data from more than 70,000 cells in a 1mm3 cube of visual cortex. After we performed functional calcium imaging in vivo, the same volume was sliced and imaged at nanometer resolution with electron microscopy at the Allen Institute (team led by Nuno Da Costa and Clay Reid). Subsequently, every cell, axon, dendrite, and synapse will be reconstructed from EM images by Sebastian Seung’s group at Princeton.
Long Range Circuit Motifs
Using advanced intersectional viral techniques, we can label neurons that are connected across widely-separated cortical areas and subcortical structures and measure their functional properties. By restricting our analysis to small populations of cells that we know are connected, we can begin to understand how connectivity and functional properties are related in the brain.
- Assistant Professor