Abstract
Neuromodulatory systems are essential for remodeling glutamatergic connectivity during experience-dependent cortical plasticity. This permissive/enabling function of neuromodulators has been associated with their capacity to facilitate the induction of Hebbian forms of long-term potentiation (LTP) and depression (LTD) by affecting cellular and network excitability. In vitro studies indicate that neuromodulators also affect the expression of Hebbian plasticity in a pull-push manner: receptors coupled to the G-protein Gs promote the expression of LTP at the expense of LTD, and Gq-coupled receptors promote LTD at the expense of LTP. Here we show that pull-push mechanisms can be recruited in vivo by pairing brief monocular stimulation with pharmacological or chemogenetical activation of Gs- or Gq-coupled receptors to respectively enhance or reduce neuronal responses in primary visual cortex. These changes were stable, inducible in adults after the termination of the critical period for ocular dominance plasticity, and can rescue deficits induced by prolonged monocular deprivation.
Highlights
Sensory experience can shape cortical circuitry and function
We evaluated the pull-push neuromodulation of plasticity in vivo in the mouse visual cortex
We asked whether combining monocular stimulation or deprivation with the manipulation of G-protein coupled receptors (GPCRs) affects visual cortical responses in a manner predicted by the pull-push model, that is Gq-coupled receptors promoting depression and Gs-coupled receptors promoting potentiation
Summary
Sensory experience can shape cortical circuitry and function. One clear demonstration of this is seen the visual cortex during a postnatal critical period, when brief visual deprivation in one eye can reduce the cortical responsiveness to the deprived eye while increasing the responsiveness to the fellow eye (for recent reviews see Espinosa and Stryker, 2012; Hensch and Quinlan, 2018). Neuromodulators can control the expression of synaptic plasticity, affecting its gain and polarity. These effects on the expression of synaptic plasticity result from the activation of distinct G-protein coupled receptors (GPCRs). An attractive consequence of the pull-push rule is the wide range of possible outcomes, from and LTP-only state when activity of Gs dominates, to an LTD-only state when Gq dominates (Huang et al, 2010, 2012, 2013). The pull-push neuromodulation of LTP/D by the balance of Gs/Gq activity could serve as a metaplasticity mechanism allowing a rapid reconfiguration of the plastic state of cortical synapses
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
