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SUMMARY:From systematic interneuron perturbations to connectome-constraine
 d dynamics
DTSTART:20260609T113000
DTEND:20260609T123000
DTSTAMP:20260603T050527Z
UID:566323f0cda2f32f662887fc917028414866e3631e01cfddc08c1905
CATEGORIES:Conferences - Seminars
DESCRIPTION:Alisa Gross <alice.gross@epfl.ch>\nQuantitative understanding 
 of neural control over behavior requires characterizing computations perfo
 rmed along information-processing pathways. In principle\, Caenorhabditis 
 elegans is ideally suited for this goal since it generates non-trivial\, c
 ontext-dependent behavior with a relatively small nervous system. Existing
  anatomical and functional connectomes represent major advances but also m
 iss important synaptic details and critical connectivities\, respectively.
  Whole-brain functional imaging\, another important approach\, by itself o
 nly reveals correlations. A perturbation-based\, causal atlas is needed to
  pin down neuronal computations in the context of behavior\, including red
 undancies\, synergies\, and time constants. We sought to satisfy this need
  through systematic chemogenetic perturbation\, combined with connectome-c
 onstrained generative modeling. Using reversible chemogenetic silencing co
 mbined with whole-brain calcium imaging\, we silenced seven head interneur
 ons individually and in pairs: two act as opposing controllers of forward-
 reverse states\, interneuron activity predicts behavior at lags of 15-25 s
 econds\, and pairwise silencing reveals structured non-additivity. In para
 llel\, we developed a connectome-constrained recurrent dynamical system tr
 ained on freely-behaving whole-brain recordings\, with three current layer
 s (gap-junction\, fast-synaptic\, extrasynaptic) and multi-timescale kinet
 ics. On a 40-animal cohort\, our architecture beats unconstrained baseline
 s\, ties anatomy-masked models on neural prediction\, and transfers across
  animals by relabeling parameters alone\, while anatomy-masked baselines c
 ollapse to negative R^2. Three independent analyses recover the canonical 
 locomotor circuit without being built in. The two approaches converge on t
 he same interneuron\, identified by silencing as a key modulator of revers
 al behavior. Our work demonstrates advantages of integrating cell-specific
  perturbation with connectome-constrained modeling\, and motivates extendi
 ng this approach to larger nervous systems.
LOCATION:GA 3 21 https://plan.epfl.ch/?room==GA%203%2021
STATUS:CONFIRMED
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