Shiyong Huang
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Researcher at Program in Neuroscience, Hussman Institute for Autism
Cortical synapses exhibit a marked short-term depression (STD) during sustained activation, largely due to the depletion of synaptic resources (vesicles). In most excitatory synapses the rate of replenishment of depleted vesicles is constant, determining an inverse relationship between the STD level and the activation rate, which theoretically, severely limits rate coding capabilities in these synapses. In contrast STD in inhibitory synapses made by parvalbumin-positive interneurons (PV-INs) is less affected by usage. We examined STD of the PV-IN to Pyramidal cell synapse in the mouse visual cortex, and found that in these synapses the recovery of depleted resources is not constant but increases linearly with the frequency of use. By combining modeling, dynamic clamp and optogenetics, we demonstrated that this dynamic regulation of recovery enables PV-INs to reduce pyramidal cell firing in a linear manner, which, theoretically, is crucial for controlling the gain of cortical visual responses.
eLife, 2020-05-20
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 can 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 LTD. Here we show that the pull-push mechanism 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 visual cortical responses. These changes were stable, can be induced in adults after the termination of the critical period for juvenile ocular dominance plasticity, and can rescue deficits induced by prolonged monocular deprivation.