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The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus
Journal article   Open access   Peer reviewed

The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus

E Anne Martin, Shruti Muralidhar, Zhirong Wang, Diégo Cordero Cervantes, Raunak Basu, Matthew R Taylor, Jennifer Hunter, Tyler Cutforth, Scott A Wilke, Anirvan Ghosh, …
eLife, Vol.4(2015), pp.e09395-e09395
11/17/2015
DOI: 10.7554/eLife.09395
PMCID: PMC4642954
PMID: 26575286
url
https://doi.org/10.7554/eLife.09395View
Published (Version of record) Open Access

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Abstract

Synaptic target specificity, whereby neurons make distinct types of synapses with different target cells, is critical for brain function, yet the mechanisms driving it are poorly understood. In this study, we demonstrate Kirrel3 regulates target-specific synapse formation at hippocampal mossy fiber (MF) synapses, which connect dentate granule (DG) neurons to both CA3 and GABAergic neurons. Here, we show Kirrel3 is required for formation of MF filopodia; the structures that give rise to DG-GABA synapses and that regulate feed-forward inhibition of CA3 neurons. Consequently, loss of Kirrel3 robustly increases CA3 neuron activity in developing mice. Alterations in the Kirrel3 gene are repeatedly associated with intellectual disabilities, but the role of Kirrel3 at synapses remained largely unknown. Our findings demonstrate that subtle synaptic changes during development impact circuit function and provide the first insight toward understanding the cellular basis of Kirrel3-dependent neurodevelopmental disorders.
 Animals Cell Line Gene Knockout Techniques Hippocampus - embryology Hippocampus - physiology Membrane Proteins - deficiency Membrane Proteins - metabolism Mice Mice, Knockout Mossy Fibers, Hippocampal - metabolism Neurons - physiology Rats Synapses - metabolism

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