Abstract
Dendritic spine generation and elimination play an important role in learning and memory, the dynamics of which have been examined within the neocortex in vivo. Spine turnover has also been detected in the absence of specific learning tasks, and is frequently exaggerated in animal models of autistic spectrum disorder (ASD). The present study aimed to examine whether the baseline rate of spine turnover was activity-dependent. This was achieved using a microfluidic brain interface and open-dura surgery, with the goal of abolishing neuronal Ca2+ signaling in the visual cortex of wild-type mice and rodent models of fragile X syndrome (Fmr1 knockout [KO]). In wild-type and Fmr1 KO mice, the majority of baseline turnover was found to be activity-independent. Accordingly, the application of matrix metalloproteinase-9 inhibitors selectively restored the abnormal spine dynamics observed in Fmr1 KO mice, without affecting the intrinsic dynamics of spine turnover in wild-type mice. Such findings indicate that the baseline turnover of dendritic spines is mediated by activity-independent intrinsic dynamics. Furthermore, these results suggest that the targeting of abnormal intrinsic dynamics might pose a novel therapy for ASD.
Highlights
The majority of excitatory synaptic contacts are formed by small dendritic protrusions in the cerebral cortex, commonly referred to as dendritic spines
Fmr[1] knockout (KO) mice present with many of the neural abnormalities observed in patients with fragile X syndrome, including abnormalities in dendritic spine morphology, synaptic plasticity, and learning and memory[14,15,16,17,18]
No studies have examined whether the increased rate of baseline turnover observed in autistic spectrum disorder (ASD) models reflects activity-dependent plasticity or activity-independent intrinsic dynamics, and the mechanism responsible for increased spine turnover in ASD models remains largely elusive
Summary
The majority of excitatory synaptic contacts are formed by small dendritic protrusions in the cerebral cortex, commonly referred to as dendritic spines. Spine turnover has been traditionally observed following activity-dependent plasticity induced by cytosolic increases in Ca2+ concentration[2,6,7], but has been identified in the absence of specific learning tasks[3,8]. Such intrinsic dynamics are reported to occur in vitro in a Ca2+-independent manner[7,9,10]. Fmr[1] knockout (KO) mice present with many of the neural abnormalities observed in patients with fragile X syndrome, including abnormalities in dendritic spine morphology, synaptic plasticity, and learning and memory[14,15,16,17,18]. As MMP9 inhibitors have been linked to changes in spine structure[22,23,24], the effect of MMP9 inhibitor administration was investigated with regard to increased spine turnover in Fmr[1] KO and wild-type mice
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.
