Disruption of cortical circuitry development in glycine receptor alpha 2 knockout mice
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1
UHasselt, Belgium
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2
ULg, Belgium
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3
SickKids, Canada
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4
VUB, Belgium
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5
WELBIO, Belgium
Previous studies have revealed an important role of strychnine-sensitive glycine receptors (GlyRs) in the cerebral cortex during neurogenesis. Specifically, absence of GlyR alpha 2 subunits in a genetically disrupted mouse model leads to defects in the interneuronal migration and proliferation of projection neurons. In order to evaluate the long-term consequences of these early defects, we examined the role of GlyRs during postnatal development of the cerebral cortex. Remarkably, GlyR alpha 2 knockout mice displayed a significant reduction in the number of parvalbumin positive interneurons at postnatal day 14 associated with a reduction of upper layer and layer V projection neurons of the cortex. Moreover, morphological and synaptic defects were assessed in the cerebral cortex of knockout mice by performing 3D reconstruction of single neurons and whole-cell patch-clamp recordings. Morphological studies of biocytin-filled neurons revealed altered dendrites growing and generation of spines. Furthermore, whole-cell recordings showed a substantial decrease in the frequency of inhibitory post-synaptic currents (IPSCs) and increase of excitatory postsynaptic currents (EPSCs). Taken together, these developmental defects in the fine tuning lead to a high susceptibility of GlyRa2KO mice to epileptic seizure. These preliminary findings are consistent with the idea that GlyRs might have an important role during the development of the cortical circuitry.
References
Avila, A., et al., Glycine receptors control the generation of projection neurons in the developing cerebral cortex. Cell Death Differ, 2014. 21(11): p. 1696-708.
Avila, A., et al., Glycine receptor alpha2 subunit activation promotes cortical interneuron migration. Cell Rep, 2013. 4(4): p. 738-50.
Keywords:
glycine receptors,
Synaptic Transmission,
development,
Cortex,
Interneurons,
projection neurons
Conference:
11th National Congress of the Belgian Society for Neuroscience, Mons, Belgium, 22 May - 22 May, 2015.
Presentation Type:
Poster presentation
Topic:
Neuroscience
Citation:
Morelli
G,
Avila
A,
Aourz
N,
Smolders
IJ,
Brône
B,
Nguyen
L and
Rigo
J
(2015). Disruption of cortical circuitry development in glycine receptor alpha 2 knockout mice.
Front. Neurosci.
Conference Abstract:
11th National Congress of the Belgian Society for Neuroscience.
doi: 10.3389/conf.fnins.2015.89.00012
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Received:
05 May 2015;
Published Online:
05 May 2015.
*
Correspondence:
Dr. Giovanni Morelli, UHasselt, Diepenbeek, Belgium, Giovanni.morelli85@gmail.com