Research
Our overarching goal is to understand how our brains perform the complex computations that govern our behavior and how our experiences reshape these computations through the process of learning. Ultimately we hope to use the knowledge to better understand how the brain’s normal functions breakdown during the development of psychiatric conditions, such as addiction and depression, to inform the development of new treatment strategies.
Our Strategy and Focus
The brain’s computations originate within individual neurons, where they integrate hundreds to thousands of synaptic inputs carrying different streams of information into a single output. Because of this, we believe that in order to fully understand how computations emerge within neural circuits, where information is passed from neuron to neuron, it is necessary to understand how synapses give rise to the encoding properties of neurons. However, because neural computations arise from our interactions with the world, this necessitates we study synaptic function during active behavior to determine how they underlie neural encoding and computation, which has been difficult to achieve using traditional electrophysiology approaches. To overcome this, we utilize optical physiological approaches to dissect synaptic function and plasticity with single synapse resolution in actively behaving and learning animals. We are currently focused on trying to understand how synaptic function and plasticity underlie neural computations within the prefrontal cortex and striatum that contribute to associative learning and decision making processes. In addition, we are also trying to understand how synapses become dysregulated in these circuits from exposure to various drugs of abuse and how this dysregulation disrupts normal neural computations to lead to addiction-related behaviors. However, we are broadly interested in understanding how synaptic function shapes neural computations and behavior are are open to new areas of study through collaborations.
Our Approaches
In Vivo Synaptic Imaging
We utilize in vivo two-photon microscopy to image a variety of different activity-related signals, such as neurotransmitters, calcium, and voltage, with single synapses resolution. We image these signals in a multiplexed manner to determine how they interact to related to synaptic and neural function
In Vivo Population Imaging
We also use in vivo two-photon microscopy to image the activity of large neural populations to examine how circuits perform different computations. We further combine this approach with manipulations of synaptic function and plasticity to relate these processes to circuit computation.
Optogenetics and Other Manipulations
We use optogenetics to manipulate the activity of neurons, dendrites, and synapses in combination with in vivo imaging. In addition, we use other optical and genetic manipulations targeting intracellular signaling pathways, such as CaMKII, to determine how these pathways contribute to synaptic and neural function.
Auxiliary Approaches
In addition to our core in vivo experimental approaches, we also use a variety of in vitro methods, such as slice electrophysiology and immunohistochemistry.