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Monday July 7, 2025 10:41 - 11:10 CEST
Single-cell optogenetic perturbations reveal stimulus-dependent network interactions

Deyue Kong*1, Joe Barreto2,Greg Bond2, Matthias Kaschube1, Benjamin Scholl2

1Frankfurt Institute for Advanced Studies, Frankfurt am Main, Germany
2University of Colorado Anschutz Medical Campus, Department of Physiology and Biophysics, Aurora, Colorado, USA

*Email: kong@fias.uni-frankfurt.de


Introduction
Cortical computations arise through neuronal interactions and their dynamic reconfiguration in response to changing sensory contexts. Cortical interactions are proposed to engage distinct operational regimes that either amplify or suppress particular neuronal networks. A recent study in mouse primary visual cortex (V1) found competitive, suppressive interactions between nearby, similarly-tuned neurons, with exception of highly-correlated neuronal pairs showing facilitatory coupling [1]. It remains unclear whether such feature competition generalizes to cortical circuits with topographic organization, where neighboring neurons within columns exhibit similar tuning to visual features, and distal excitatory axons preferentially target similarly-tuned columns.
Methods
We investigated interactions between excitatory neurons in the ferret V1 and how network interactions depend on stimulus strength (contrast). We recorded the responses of layer 2/3 neurons to drifting gratings of eight directions at two contrast levels using 2-photon calcium imaging, while activating individual excitatory neurons with precise 2-photon optogenetics. We statistically quantified the effect of target photostimulation on neural activity (inferred spike rate) during visual stimulation using a Poisson generalized linear model (GLM). We then used our model to estimate a target’s influence on the surrounding neurons’ activity and their stimulus coding properties.
Results
Our analyses revealed interactions that depended on cortical distance, stimulus properties, and functional similarity between neuron pairs. Influence of photostimulated neurons strongly depended on cortical distance, but overall exhibited net suppression. Suppression was weakest between nearby neurons (<100µm), but was found across large cortical distances. Distant-dependent suppression was reduced when visual stimuli were low contrast. Examining functional-similar neurons, we found that noise correlations between neuron pairs were most predictive of measured interactions, showing a strong shift from amplification to competition: at low contrast, we observed local amplification between noise-correlated excitatory neurons, but increasing contrast led to a predominantly suppressive influence across all distances.
Discussion
Our data support predictions from theoretical models, such as stabilized supralinear networks (SSN), in which networks amplify weak feed-forward input, but sublinearly integrate strong inputs [2,3]. Furthermore, decoding analyses suggest that the contrast-dependent shift from facilitation to suppression correlates with improved decoding accuracy of direction. These findings demonstrate that stimulus contrast dynamically modulates recurrent interactions between excitatory neurons in ferret V1, likely by differentially engaging inhibitory neurons. Such dynamic modulation supports optimal encoding of sensory information within columnar cortices.




Acknowledgements

References
[1] Chettih, SN, Harvey, CD. Single-neuron perturbations reveal feature-specific competition in V1. Nature (2019).doi:10.1038/s41586-019-0997-6
[2] Rubin DB, Van Hooser SD, Miller KD. The stabilized supralinear network: a unifying circuit motif underlying multi-input integration in sensory cortex. Neuron(2015) doi: 10.1016/j.neuron.2014.12.026. PMID: 25611511; PMCID: PMC4344127.
[3] Heeger DJ, Zemlianova KO. A recurrent circuit implements normalization, simulating the dynamics of V1 activity. PNAS(2020). doi: 10.1073/pnas.2005417117. . PMID: 32843341; PMCID: PMC7486719.
Speakers
Monday July 7, 2025 10:41 - 11:10 CEST
Auditorium - Plenary Room

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