Optimizing optogenetic stimulation protocols in auditory corticofugal neurons based on closed-loop spike feedback
Optimizing optogenetic stimulation protocols in auditory corticofugal neurons based on closed-loop spike feedback
Abstract Optogenetics provides a means to probe functional connections between brain areas. By activating a set of presynaptic neurons and recording the activity from a downstream brain area, one can establish the sign and strength of a feedforward connection. One challenge is that there are virtually limitless patterns that can be used to stimulate a presynaptic brain area. Functional influences on downstream brain areas can depend not just on whether presynaptic neurons were activated, but how they were activated. Corticofugal axons from the auditory cortex (ACtx) heavily innervate the auditory tectum, the inferior colliculus (IC). Despite the anatomical weight of this connection, optogenetic activation of ACtx neurons produced only modest changes in the IC neuron firing rates. To determine whether different modes of cortical activation could more faithfully reveal the strength of feedforward connectivity, we employed a closed-loop evolutionary optimization procedure that tailored voltage command signals to the laser based on firing rate variations recorded from single units in the IC of awake male and female mice. Within minutes, the evolutionary search procedure converged on ACtx stimulation configurations that produced more effective and widespread enhancement of IC unit activity than generic activation parameters. Cortical modulation of midbrain spiking was bi-directional, as the evolutionary search procedure could be programmed to converge on activation patterns that suppressed or enhanced sound-evoked IC firing rate. These findings demonstrate that the feedforward influence between brain areas can vary both in sign and degree depending on how presynaptic neurons are activated in time. Significance StatementNeurons in deep layers of the auditory cortex (ACtx) make extensive projections to subcortical auditory areas, yet little is known about how these descending projections modulate subcortical sound processing in real time. Here, we leveraged recent advances in multi-channel electrophysiology and optogenetics to record from multiple regions of the inferior colliculus (IC) while optogenetically stimulating cortical neurons expressing Chronos, an ultra-fast channelrhodopsin. To identify ACtx activation patterns associated with the strongest effects on IC firing rates, we applied a machine learning algorithm that utilized the firing rate of single IC neurons to iteratively tailor the voltage command signal sent to the laser. We show that the temporal patterning of ACtx spiking strongly impacts the cortical influence on midbrain sound processing.
Polley Daniel B、Hancock Kenneth E、Williamson Ross S、Vila Charles-Henri
Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary||Dept. Otolaryngology, Harvard Medical SchoolEaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary||Dept. Otolaryngology, Harvard Medical SchoolEaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary||Dept. Otolaryngology, Harvard Medical SchoolEaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary||Bertarelli Fellows Program, Ecole Polytechnique
生物科学研究方法、生物科学研究技术神经病学、精神病学生理学
Polley Daniel B,Hancock Kenneth E,Williamson Ross S,Vila Charles-Henri.Optimizing optogenetic stimulation protocols in auditory corticofugal neurons based on closed-loop spike feedback[EB/OL].(2025-03-28)[2025-04-30].https://www.biorxiv.org/content/10.1101/505214.点此复制
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