TY  - JOUR
A1  - Bissen, Diane
A1  - Kracht, Maximilian Ken
A1  - Foß, Franziska
A1  - Hofmann, Jan
A1  - Acker-Palmer, Amparo
T1  - EphrinB2 and GRIP1 stabilize mushroom spines during denervation-induced homeostatic plasticity
T2  - Cell Reports
N2  - Highlights
• Denervation induces mushroom spine loss and AMPAR redistribution to the surface
• GRIP1 and ephrinB2 mediate homeostatic mechanisms after lesion
• Stimulation with the ephrinB2 receptor EphB4 promotes a surface shift of AMPARs
• AMPARs surface shift restores impaired spine recovery after lesion in GRIP1 mutants
Summary
Despite decades of work, much remains elusive about molecular events at the interplay between physiological and structural changes underlying neuronal plasticity. Here, we combined repetitive live imaging and expansion microscopy in organotypic brain slice cultures to quantitatively characterize the dynamic changes of the intracellular versus surface pools of GluA2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) across the different dendritic spine types and the shaft during hippocampal homeostatic plasticity. Mechanistically, we identify ephrinB2 and glutamate receptor interacting protein (GRIP) 1 as mediating AMPAR relocation to the mushroom spine surface following lesion-induced denervation. Moreover, stimulation with the ephrinB2 specific receptor EphB4 not only prevents the lesion-induced disappearance of mushroom spines but is also sufficient to shift AMPARs to the surface and rescue spine recovery in a GRIP1 dominant-negative background. Thus, our results unravel a crucial role for ephrinB2 during homeostatic plasticity and identify a potential pharmacological target to improve dendritic spine plasticity upon injury.
KW  - GRIP1
KW  - ephrinB2
KW  - EphB4
KW  - AMPA receptors
KW  - homeostatic plasticity
KW  - denervation
KW  - mushroom spines
KW  - hippocampus
KW  - expansion microscopy
KW  - organotypic slice cultures
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77944
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-779447
SN  - 2211-1247
VL  - 34
IS  - 13, art. 108923
SP  - 1
EP  - 11
PB  - Elsevier
CY  - Amsterdam
ER  -