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Transcript
A theoretical framework for optogenetic perturbations in the
oculomotor integrator
Nuno Calaim*, David Barrett*, Pedro J. Goncalves*, Sophie Deneve, Christian K. Machens
Computational and Systems Neuroscience (CoSyNe), 2015
How do neural networks respond to instantaneous perturbations of their activity? This question
has been the subject of intense investigation ever since the advent of optogenetic perturbation
techniques, which allow us to instantaneously perturb neural activity and record the response. We
do not yet have a theoretical framework to adequately describe the neural response to such
optogenetic perturbations, nor do we understand how neural networks can perform computations
amid a background of on-going natural perturbations.
In this work, we develop a framework to describe the impact of optogenetic perturbations on the
oculomotor integrator (OI). The OI is a neural structure in the hindbrain which is responsible for
controlling eye position by integrating eye movement signals to produce eye position signals. We
build a spiking network model of the OI from first principles, following the approach of Boerlin
et al. 2013. Specifically, we postulate that the connectivity and dynamics of neurons in OI are
optimized to represent eye movement signals using a linear decoder (analogous to a dendritic
summation). The resulting spiking network replicates key properties of the OI, such as the typical
distribution of tuning curves and accurate eye position representation (Aksay et al. 2000, 2004).
We can now do simulated optogenetics in our model: we artificially perturb membrane voltages
and record the impact of these perturbations. We find that changes in eye position in our model
are consistent with recent optogenetic experiments in which the OI was perturbed with
Halorhodopsin and Channelrhodopsin (Goncalves et al. 2014). This indicates that the OI acts to
instantaneously adjust the activities of the unperturbed neurons in order to compensate for any
error in the computation performed by the OI. More generally, these results suggest that our
framework may provide a useful and timely tool for characterizing the impact of optogenetic
manipulations.
(* authors contributed equally)