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Over-expression of the DCLK gene transcript CARP decreases CA3/CA1 network excitability
Geert J Schenk1, Taco Werkman, Wytse Wadman
1Division of Medical Pharmacology, Leiden/Amsterdam Centre for Drug Research/Leiden University Medical Centre, Einsteinweg 55, Leiden, The Netherlands. g.j.schenk@LACDR.leidenuniv.nl
Brain Research
|July 28, 2010
Summary
The CaMK Related Peptide (CARP) affects adult brain function by altering hippocampal network excitability and glutamatergic transmission, particularly after neurological stimuli.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The Doublecortin Like Kinase (DCLK) gene is crucial for brain development.
- A specific DCLK splice variant, CaMK Related Peptide (CARP), is expressed in adults following neurological events.
- The precise role of CARP in the adult brain remains largely unknown.
Purpose of the Study:
- To investigate the function of CARP in the adult hippocampus.
- To characterize the effects of CARP overexpression on hippocampal network activity.
Main Methods:
- Generation of transgenic mice overexpressing CARP in the brain.
- Electrophysiological recordings of the CA3/CA1 hippocampal network.
- Analysis of protein expression levels (calretinin, Rapgef4).
Main Results:
- Overexpression of CARP significantly increased field excitatory post-synaptic potentials (fEPSPs) in the CA3/CA1 network.
- Hippocampal CA3/CA1 network excitability was reduced in CARP-overexpressing mice.
- Calretinin expression was upregulated, while Rapgef4 was downregulated in the hippocampus.
Conclusions:
- CARP influences glutamatergic neuronal transmission in the adult hippocampus.
- CARP plays a role in the brain's response to neurological stimuli.
- CARP may modulate neuronal excitability through downstream targets like calretinin and Rapgef4.
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