Vertebrate Intersectinl Is Repurposed to Facilitate Cortical Midline Connectivity and Higher Order Cognition.
In: Journal of Neuroscience, Jg. 33 (2013-02-27), Heft 9, S. 4055-4065
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Zugriff:
Invertebrate studies have highlighted a role for EH and SH3 domain Intersectin (Itsn) proteins in synaptic vesicle recycling and mor-phology. Mammals have two Itsn genes (Itsnl and Itsn2), both of which can undergo alternative splicing to include DBL/PH and C2 domains not present in invertebrate Itsn proteins. To probe for specific and redundant functions of vertebrate Itsn genes, we generated Itsn I, Itsn2, and double mutant mice. While invertebrate mutants showed severe synaptic abnormalities, basal synaptic transmission and plasticity were unaffected at Schaffer CA1 synapses in mutant mice. Surprisingly, intercortical tracts--corpus callosum, ventral hip-pocampal, and anterior commissures--failed to cross the midline in mice lacking Itsnl, but not Itsn2. In contrast, tracts extending within hemispheres and those that decussate to more caudal brain segments appeared normal. Itsnl mutant mice showed severe deficits in Morris water maze and contextual fear memory tasks, whereas mice lacking Itsn2 showed normal learning and memory. Thus, coincident with the acquisition of additional signaling domains, vertebrate Itsn 1 has been functionally repurposed to also facilitate interhemispheric connectivity essential for high order cognitive functions. [ABSTRACT FROM AUTHOR]
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Vertebrate Intersectinl Is Repurposed to Facilitate Cortical Midline Connectivity and Higher Order Cognition.
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Autor/in / Beteiligte Person: | Sengar, Ameet S. ; Ellegood, Jacob ; Yiu, Adelaide P. ; Wang, Hua ; Wang, Wei ; Juneja, Subhash C. ; Lerch, Jason P. ; Josselyn, Sheena A. ; Henkelman, R. Mark ; Salter, Michael W. ; Egan, Sean E. |
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Zeitschrift: | Journal of Neuroscience, Jg. 33 (2013-02-27), Heft 9, S. 4055-4065 |
Veröffentlichung: | 2013 |
Medientyp: | academicJournal |
ISSN: | 0270-6474 (print) |
DOI: | 10.1523/JNEUROSCI.4428-12.2013 |
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