Memories are stored in sparsely distributed neural ensembles called “engrams”. These are ensembles of cells that fire together during a learning experience and later reactivate during recall. Each engram forms an integrated network spanning multiple brain regions (such as the hippocampus, amygdala, and cortex) and even includes non-neuronal support cells like astrocytes.

One of our fundamental questions is why certain neurons get recruited into a new memory circuit while neighboring neurons do not. Emerging evidence shows neurons with inherently higher excitability have an advantage in being selected, and indeed they undergo lasting structural and molecular changes once a memory is formed. Critically, silencing these specific “engrams” can block retrieval of the memory, whereas reactivating them later can bring it back even in the absence of the original cue.

Unlike a fixed snapshot, memory circuits are continuously remodeled by time and experience. During systems consolidation, a hippocampal trace is progressively re-expressed in distributed cortical hubs—a process still debated in detail. The memory’s representation migrates across regions, preserving content while rewiring circuitry. Moreover, each time we recall a memory or learn something new related to it, the neural ensemble can be further updated and reconfigured. In this way, memories are continuously refined (or sometimes distorted) by subsequent experiences.

To unravel these processes, we are developing high-throughput tools to map and manipulate memory circuits at single-cell resolution. We apply these techniques in models of healthy aging and in neurodegenerative disease to pinpoint how memory networks change when the brain ages or becomes ill. In disorders such as Alzheimer’s disease, for example, the reactivation of engram cells is impaired, contributing to memory loss. By understanding how engrams assemble, persist, and fail, we aim to identify new strategies to preserve memories and treat dementia.

Adipose tissue—once seen merely an energy reservoir—is now recognized as a dynamic endocrine organ that actively communicates with the nervous system. Through this two-way neuro-fat dialogue, the brain and body fat constantly exchange signals to coordinate energy balance. For example, sympathetic nerve fibers that innervate white and brown fat release norepinephrine to trigger fat breakdown (lipolysis) and heat production (thermogenesis). On the flip side, sensory nerves embedded within fat relay information back to the brain about the tissue’s condition – reporting on lipid reserves, inflammation levels, and even mechanical stretch, as emerging evidence suggests. Together, this feedback loop between fat and brain helps maintain overall energy homeostasis.

Neural control of fat is remarkably adaptable. For instance, exposure to cold amplifies sympathetic activity and even spurs new nerve growth into adipose tissue. This boosts the tissue’s capacity for burning fuel and generating heat. In contrast, chronic overeating and inflammation can impair this neural–fat connection. Such stress can lead to adipose neuropathy – a degeneration or silencing of the nerves within fat and predisposes the body toward insulin resistance and metabolic dysfunction.

These stark differences raise a critical question: what causes fat’s nerves to flourish under some conditions but degenerate under others? We hypothesize that specific sub-circuits of sympathetic and sensory nerves – defined by their molecular identities and projection patterns – are differentially engaged by challenges such as fasting, exercise, cold, or overeating. One pathway may drive thermogenesis in winter; another may mobilize fuel during scarcity. Revealing how these nerve fibers integrate nutritional, hormonal, and immune signals will shed light on how the nervous system choreographs fat mobilization, thermogenesis, and glucose regulation.

To answer these questions, we are developing an integrative toolkit that combines neural circuit tracing with single-cell and spatial transcriptomics. Using these methods, we are assembling a wiring-and-molecular atlas of the neuro-adipose interface to track how connections form, remodel, and degenerate. This comprehensive map will allow us to pinpoint molecular checkpoints that could be targeted to rewire fat innervation therapeutically. Ultimately, such insights will pave the way for new strategies to combat obesity and type 2 diabetes.