| First Author | Zhong LR | Year | 2018 |
| Journal | J Neurosci | Volume | 38 |
| Issue | 49 | Pages | 10454-10466 |
| PubMed ID | 30355624 | Mgi Jnum | J:267659 |
| Mgi Id | MGI:6260136 | Doi | 10.1523/JNEUROSCI.1133-18.2018 |
| Citation | Zhong LR, et al. (2018) Retinoic Acid Receptor RARalpha-Dependent Synaptic Signaling Mediates Homeostatic Synaptic Plasticity at the Inhibitory Synapses of Mouse Visual Cortex. J Neurosci 38(49):10454-10466 |
| abstractText | Homeostatic synaptic plasticity is a synaptic mechanism through which the nervous system adjusts synaptic excitation and inhibition to maintain network stability. Retinoic acid (RA) and its receptor RARalpha have been established as critical mediators of homeostatic synaptic plasticity. In vitro studies reveal that RA signaling enhances excitatory synaptic strength and decreases inhibitory synaptic strength. However, it is unclear whether RA-mediated homeostatic synaptic plasticity occurs in vivo, and if so, whether it operates at specific types of synapses. Here, we examine the impact of RA/RARalpha signaling in the monocular zone of primary visual cortex (V1m) in mice of either sex. Exogenous RA treatment in acute cortical slices resulted in a reduction in mIPSCs of layer 2/3 pyramidal neurons, an effect mimicked by visual deprivation induced by binocular enucleation in postcritical period animals. Postnatal deletion of RARalpha blocked RA's effect on mIPSCs. Cell type-specific deletion of RARalpha revealed that RA acted specifically on parvalbumin (PV)-expressing interneurons. RARalpha deletion in PV(+) interneurons blocked visual deprivation-induced changes in mIPSCs, demonstrating the critical involvement of RA signaling in PV(+) interneurons in vivo Moreover, visual deprivation- or RA-induced downregulation of synaptic inhibition was absent in the visual cortical circuit of constitutive and PV-specific Fmr1 KO mice, strongly suggesting a functional interaction between fragile X mental retardation protein and RA signaling pathways. Together, our results demonstrate that RA/RARalpha signaling acts as a key component for homeostatic regulation of synaptic transmission at the inhibitory synapses of the visual cortex.SIGNIFICANCE STATEMENT In vitro studies established that retinoic acid (RA) and its receptor RARalpha play key roles in homeostatic synaptic plasticity, a mechanism by which synaptic excitation/inhibition balance and network stability are maintained. However, whether synaptic RA signaling operates in vivo remains undetermined. Here, using a conditional RARalpha KO mouse and cell type-specific Cre-driver lines, we showed that RARalpha signaling in parvalbumin-expressing interneurons is crucial for visual deprivation-induced homeostatic synaptic plasticity at inhibitory synapses in visual cortical circuits. Importantly, this form of synaptic plasticity is absent when fragile X mental retardation protein is selectively deleted in parvalbumin-expressing interneurons, suggesting a functional connection between RARalpha and fragile X mental retardation protein signaling pathways in vivo Thus, dysfunction of RA-dependent homeostatic plasticity may contribute to cortical circuit abnormalities in fragile X syndrome. |
