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Evaluation of Synapse Density in Hippocampal Rodent Brain Slices
Published on: October 6, 2017
DPP6 regulation of dendritic morphogenesis impacts hippocampal synaptic development
Lin Lin1, Wei Sun, Ben Throesch
1Molecular Neurophysiology and Biophysics Section, Program in Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Nature Communications
|August 6, 2013
Summary
Dipeptidyl-peptidase 6 is crucial for dendritic filopodia formation and stability in developing neurons. Its absence impairs neuronal branching, spine density, and synaptic function, independent of Kv4.2 channels.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Dipeptidyl-peptidase 6 (DPP6) is an auxiliary subunit of Kv4 potassium channels.
- DPP6 gene variations are linked to central nervous system disorders like autism and schizophrenia.
- DPP6's role in neuronal development beyond ion channel function is largely unknown.
Purpose of the Study:
- To investigate the role of dipeptidyl-peptidase 6 in early neuronal development.
- To determine the impact of DPP6 deficiency on dendritic structure and synaptic formation.
- To elucidate the molecular mechanisms underlying DPP6's function in neurons.
Main Methods:
- Genetic manipulation: utilized knockdown and genetic deletion of dipeptidyl-peptidase 6.
- Neuronal imaging: assessed dendritic branching and filopodia formation in hippocampal neurons.
- Electrophysiology: evaluated synaptic function and Kv4.2 channel activity.
Main Results:
- Neurons lacking dipeptidyl-peptidase 6 exhibited reduced dendritic branching and fewer dendritic spines.
- DPP6 deficiency led to fewer functional synapses, impacting neuronal connectivity.
- These effects were independent of the potassium channel subunit Kv4.2.
- DPP6 was found to interact with a filopodia-associated myosin and extracellular fibronectin.
Conclusions:
- Dipeptidyl-peptidase 6 plays a critical, unexpected role in dendritic filopodia formation and stability.
- DPP6 is essential for proper hippocampal synaptic development and function.
- DPP6's function extends to cell adhesion and motility, influencing neuronal architecture.
