A synaptic switch gates developmentally-regulated homeostatic plasticity in parvalbumin interneurons of the visual cortex

DRUART M; SOIZA REILLY M; QUAGGETTO M; GARCIA M; MOUTKINE I; LE MAGUERESSE C

Chicago

Congreso; Society for Neuroscience meeting; 2019

SFN

Braindevelopment is shaped by synaptic plasticity, which contributes to theformation of mature neuronal networks. Critical periods (CP) of braindevelopment are specific time windows characterized by high plasticity inneural networks in response to environmental perturbations. A specific CP hasbeen well characterized in the developing visual cortex where permanent changes inocular dominance (OD) occur after monocular deprivation (MD) during CP.Converging evidence implicates glutamatergic inputs onto parvalbumin-expressing(PV) interneurons in the onset of the CP for OD plasticity. However, theunderlying molecular and synaptic mechanisms remain largely unknown.Using patch-clamp recordings in acute slices from mice at differentdevelopmental stages, we studied the development of the glutamatergic inputonto PV interneurons. Our results revealed a transient decrease in theAMPA-receptor (AMPAR) rectification index during CP. This suggests a transientloss of AMPAR subunit GluA2 at excitatory synapses onto PV interneurons duringCP. Interestingly expression of GRIP1, a protein involved in GluA2 trafficking,has been shown to be transiently downregulated in cortical PV interneurons atP25. Furthermore, the interaction between GRIP1 and GluA2 mediates homeostaticplasticity at glutamatergic synapses. To assess homeostatic plasticity in PVneurons, we sutured one eye for 3 days before recording miniature excitatorypostsynaptic currents (mEPSCs) in PV neurons of the contralateral visualcortex. We observed an increase in mEPSC frequency before and after CP but notduring CP. This result suggests an absence of homeostatic plasticity atexcitatory synapses onto PV interneurons selectively during CP, thuspotentially allowing profound changes in visual cortex connectivity at thiscrucial developmental stage. We hypothesized that the downregulation of GRIP1during CP prevents the trafficking of GluA2 subunit to the synapse andhomeostatic plasticity in PV interneurons during CP. To test this hypothesis,we generated PV-Cre::GRIP1lox/lox mice in which GRIP1 is ablated specificallyin PV neurons and then recorded PV neurons in the visual cortex of adult (P50) miceafter MD. The rectification index of AMPAR was decreased in adult mice lackingGRIP1 in PV neurons. In addition, MD in KO mice did not elicit the increase inmEPSC frequency observed in WT mice, indicating that GRIP1 is necessary forhomeostatic synaptic plasticity in PV neurons.Taken together, our results suggest that the transient downregulation of GRIP1prevents the homeostatic plasticity of glutamatergic inputs onto PVinterneurons in visual cortex selectively during CP.<!-- /* Font Definitions */@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:-520092929 1073786111 9 0 415 0;}@font-face{font-family:"Segoe UI";mso-font-alt:"Courier New";mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-520084737 -1073683329 41 0 479 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:107%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:Calibri;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:FR;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;font-family:Calibri;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:FR;}.MsoPapDefault{mso-style-type:export-only;margin-bottom:8.0pt;line-height:107%;}@page WordSection1{size:8.5in 11.0in;margin:1.0in 1.25in 1.0in 1.25in;mso-header-margin:.5in;mso-footer-margin:.5in;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->