Wnt-5a modulates recycling of functional GABAA receptors on hippocampal neurons.
نویسندگان
چکیده
GABA(A) receptors (GABA(A)-Rs) play a significant role in mediating fast synaptic inhibition and it is the main inhibitory receptor in the CNS. The role of Wnt signaling in coordinating synapse structure and function in the mature CNS is poorly understood. In previous studies we found that Wnt ligands can modulate excitatory synapses through remodeling both presynaptic and postsynaptic regions. In this current study we provide evidence for the effect of Wnt-5a on postsynaptic GABA(A)-Rs. We observed that Wnt-5a induces surface expression and maintenance of this receptor in the neuronal membrane. The evoked IPSC recordings in rat hippocampal slice indicate that Wnt-5a can regulates postsynaptically the hippocampal inhibitory synapses. We found also that Wnt-5a: (a) induces the insertion and clustering of GABA(A)-Rs in the membrane; (b) increases the amplitude of GABA-currents due exclusively to postsynaptic mechanisms; (c) does not affect the endocytic process, but increases the receptor recycling. Finally, all these effects on the GABA(A)-Rs are mediated by the activation of calcium/calmodulin-dependent kinase II (CaMKII). Therefore, we postulate that Wnt-5a, by activation of CaMKII, induces the recycling of functional GABA(A)-Rs on the mature hippocampal neurons.
منابع مشابه
Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons.
Wnt signaling has a crucial role in synaptic function at the central nervous system. Here we evaluate whether Wnts affect nitric oxide (NO) generation in hippocampal neurons. We found that non-canonical Wnt-5a triggers NO production; however, Wnt-3a a canonical ligand did not exert the same effect. Co-administration of Wnt-5a with the soluble Frizzled related protein-2 (sFRP-2) a Wnt antagonist...
متن کاملWnt-related SynGAP1 is a neuroprotective factor of glutamatergic synapses against Aβ oligomers
Wnt-5a is a synaptogenic factor that modulates glutamatergic synapses and generates neuroprotection against Aβ oligomers. It is known that Wnt-5a plays a key role in the adult nervous system and synaptic plasticity. Emerging evidence indicates that miRNAs are actively involved in the regulation of synaptic plasticity. Recently, we showed that Wnt-5a is able to control the expression of several ...
متن کاملCanonical Wnt signaling protects hippocampal neurons from Aβ oligomers: role of non-canonical Wnt-5a/Ca2+ in mitochondrial dynamics
Alzheimer's disease (AD) is the most common type of age-related dementia. The disease is characterized by a progressive loss of cognitive abilities, severe neurodegeneration, synaptic loss and mitochondrial dysfunction. The Wnt signaling pathway participates in the development of the central nervous system and growing evidence indicates that Wnts also regulate the function of the adult nervous ...
متن کاملModulation of septo-hippocampal Theta activity by GABAA receptors: an experimental and computational approach.
Theta frequency oscillation of the septo-hippocampal system has been considered as a prominent activity associated with cognitive function and affective processes. It is well documented that anxiolytic drugs diminish septo-hippocampal oscillatory Theta activity contributing to their either therapeutic or unwanted side effects. In the present experiments we applied a combination of computational...
متن کاملCharacterization of spontaneous network-driven synaptic activity in rat hippocampal slice cultures
A particular characteristic of the neonatal hippocampus is the presence of spontaneous network-driven oscillatory events, the so-called giant depolarizing potentials (GDPs). GDPs depend on the interplay between GABA and glutamate. Early in development, GABA, acting on GABAA receptors, depolarizes neuronal membranes via a Cl- efflux. Glutamate, via AMPA receptors, generates a positive feedback n...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of neuroscience : the official journal of the Society for Neuroscience
دوره 30 25 شماره
صفحات -
تاریخ انتشار 2010