Assistant Professor of Neurobiology
B.Sc. 2007, McGill University; Ph.D. 2014, University of British Columbia; Postdoctoral
Fellow 2015-2020, University of California, San Diego
Cellular, molecular, and genomic mechanisms underlying experience-driven synapse and
The Brigidi Lab is interested in the genomic underpinnings of sensory experience-driven
synapse and circuit plasticity. As we explore our surroundings we experience a barrage
of sensory stimuli, some salient and most irrelevant, and in response can flexibly
update our behavior. How do our brains transform fleeting, salient stimuli into long-lasting
memories and behavioral adaptations? How are incoming sensory stimuli transduced at
the level of neural circuits and synapses? What molecular mechanisms underlie the
plasticity of synapses and circuits necessary for learning and behavioral flexibility?
The most enduring forms of neuronal plasticity require regulation of the genome. Inducible
transcription factors (ITFs), a subset of immediate early genes, are rapidly expressed
in response to incoming stimuli, traffic into the nucleus and bind thousands of sites
across the genome. ITFs carefully orchestrate downstream programs of gene regulation
that impact neuronal functions and plasticity, and are therefore poised to tailor
a cell's phenotype and role within its local circuit to incoming stimuli in real time
and on a continuous basis. The lab's long-term goal is to uncover the genomic mechanisms
that form the neural basis of behavioral adaptations, and is investigating key questions
surrounding ITF biology:
- Are particular ITFs fine-tuned to specific patterns of depolarizing activity stimuli
experienced by neurons within their local circuits? What molecular pathways enable
an ITF to distinguish a salient stimulus from an irrelevant one?
- Can ITFs tailor downstream gene regulation programs to a specific stimulus? How
do the collection of genes regulated by an ITF impact synaptic and circuit plasticity?
- Is stimulus-specific ITF responsivity and downstream gene regulation also cell subtype-specific?
How might ITFs support cellular diversity in neural circuits across brain regions,
and through development?
- How does brain region- and cell subtype-specific ITF expression support learning
and experience-driven behavioral adaptions?
To answer these questions, the lab uses ex vivo whole-cell electrophysiology with
circuit manipulation techniques including pharmacology and optogenetics, combined
with biochemistry, new CRISPR/Cas9 technologies, and genome-wide sequencing. Detailed
molecular work at the level of intact neural circuits is at the core of all projects
within the lab.