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Our lab studies the neurobiology of episodic memory—memories of what happened, where, when, and with whom—which are thought to form in the hippocampus. Using virtual reality environments and head-fixed mice, we visualize activity at the level of axons, dendrites, and large neural populations as memories are formed and retrieved. We’ve developed behavioral paradigms that allow mice to form memories in virtual reality, much like they do in the real world. This approach allows us to uncover the cellular and circuit-level principles that support memory in both health and disease.
A dopaminergic axon from the Ventral Tegemental Area imaged in the hippocampus
How internal states and neuromodulation shape memory formation?
How internal states and neuromodulation shape memory formation?
The hippocampus receives neuromodulatory inputs, such as acetylcholine, norepinephrine, dopamine, and serotonin, which are shaped by internal states, including arousal, reward expectation, attention, hunger, and motivation. However, the mechanisms by which these signals influence memory formation remain poorly understood. Through imaging neuromodulatory axons in the hippocampus and using optogenetic and chemogenetic techniques, we investigate how internal states shape memory formation.
Apical tuft dendritic branches of CA1 pyramidal cells
What are the circuit computations that differentiate strong vs weak memories?
What are the circuit computations that differentiate strong vs weak memories?
What makes some memories stick while others fade? Our lab develops behavioral paradigms involving aversive and reward-associated memories in head-fixed animals to explore this question. Using dendritic imaging, we investigate the synaptic and circuit-level plasticity that distinguishes strong, persistent memories from weak, transient ones. This work aims to shed light on memory-related disorders such as PTSD and addiction, where certain memories become overly dominant and resistant to extinction.
Imaging from the same group of CA1 pyramidal cells across days
Tracking the lifespan of a memory: from formation to forgetting
Tracking the lifespan of a memory: from formation to forgetting
Two-photon calcium imaging enables high-resolution, long-term tracking of the same population of hippocampal neurons. This makes it an ideal tool for studying how memory traces evolve: from their initial formation to eventual decay. By leveraging this technique, we can observe how the neural representation of a memory changes over time. Through targeted circuit manipulations, we seek to either accelerate or prevent memory loss, providing insight into the neural mechanisms by which memories are forgotten and informing potential treatments for disorders such as dementia and Alzheimer’s disease.
Schematic of future approaches in the lab to study how diverse interneuron subtypes (orange, blue, purple) and glial cells (red) influence pyramidal cell activity (green) using cell-type-specific labeling and volumetric imaging (dashed lines) across hippocampal layers.
Beyond the Main Players: How do non-principal cells influence memory?
Beyond the Main Players: How do non-principal cells influence memory?
While hippocampal pyramidal neurons—the principal excitatory cells—have been extensively studied, the functions of non-principal cells, including diverse populations of inhibitory interneurons and glial cells, are less well characterized in the context of memory. By leveraging cell-type-specific genetic reporters, multi-wavelength volumetric imaging, and targeted circuit manipulations, we want to uncover how these non-principal cells contribute to the formation and modulation of memory. By examining how they influence the activity of principal cells and shape hippocampal circuit dynamics, our goal is to develop a more comprehensive model of memory processing, thereby revealing new therapeutic targets for memory disorders.
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