Research

Neural circuits of memory

Our brain’s cognitive abilities are the result of the collective action of neuronal populations, assembled into local and long-range circuits. Our main research interests are to understand how cortical circuits operate, by establishing links between structure and function: how the dynamic interactions of distinct cell types, guided by specific connectivity rules, generate patterns of neural activity relevant for behavior. We put a particular focus on the circuits of the hippocampus and associated neocortices to gain insights into their pivotal roles for memory, inference, and imagination.

Figure: From neural coding to dynamics: visualizing population activity and the circuits that constrain it.

We routinely record and manipulate neural activity in rodents trained to perform complex spatial behavioral tasks. We are primarily interested in the mnemonic components of navigation as a means to study memory. The questions that inspire us are broadly centered around the fundamental mechanisms governing memory formation, consolidation, and utilization within the context of complex navigation. Spatial navigation also represents a naturalistic behavior tractable in a laboratory setting, but most importantly, it engages dynamic and plastic interactions across multiple brain regions, making it an ideal experimental framework for studying in unison different elements of neural circuits:

• Neural coding — how behavior and environmental context are encoded by single neurons and ensembles.
• Connectivity — the synaptic and circuit architecture that enables specific transformations of input.
• Population dynamics — how information flows across brain regions over time.

Why this matters

Our commitment extends beyond fundamental neuroscience research. We are driven by a passion to delve into the very neurobiological nature of memories, with the ultimate goal of translating our findings into practical applications that can contribute to the development of innovative interventions and targeted therapeutics. Hippocampal circuit dysfunctions are manifested across a spectrum of brain diseases, illnesses, and even in the context of healthy aging. The findings of our research program will contribute to a more comprehensive understanding of the reasons behind why such dysfunctions lead to cognitive decline and memory loss.

How we do it

We use a large array of tools and methods. In fact, part of our research efforts focuses on developing innovative experimental approaches to more precisely record and manipulate activity and plasticity of neural circuits with single-neuron precision. A non-exhaustive list of the techniques in the lab includes: electrophysiological recordings of spikes and local field potentials; functional imaging of genetically-encoded calcium, voltage, and neurotransmitter indicators; viral tracing to map and access pathway-specific circuits; manipulation of neural activity with optogenetics and chemogenetics; spatial biology to molecularly identify specific neuron types; and computational models to help guide the next experiments.

• Two-photon calcium & voltage imaging
• Viral circuit tracing
• Single-neuron electroporation
• Optogenetics & chemogenetics
• Electrophysiology (LFP, spikes)
• Spatial biology & transcriptomics
• Computational modeling

Figure: Examples of experimental approaches from single-neuron plasmid delivery to neuromodulation during imaging.