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IMSUT & RCAST
GCOE Program Seminar
< Global Education Seminar >

Date and Time:July 1st &s_comma; 2009 (Wednesday) 17:00 -
18:00
Venue : 1st building 2F conference room&s_comma; Inst.Med.Sci&s_comma; University of
Tokyo
(Nanboku/Mita line&s_comma; Shirokane-dai station)
Speaker:Kensuke Futai
Position : Postdoctoral fellow
Affiliation:The Picower Institute for Learning and Memory&s_comma;
Department of Brain and Cognitive Sciences&s_comma; Massachusetts Institute
of Technology
Seminar Title:The roles of trans-synaptic adhesion molecules on
functional synapse formation
-Role of Neuroligin-neurexin interaction on the target synapse
recognition-
(Language:English)
Summary:
Excitatory and inhibitory inputs send axons to their target neuron
and form synaptic connections where their appropriate receptors are
located. The molecular mechanisms by which pre- and postsynaptic
specialization and development are matched and coordinated are not
well understood. Recent studies suggest that postsynaptically
expressed neuroligin isoforms (NLs) differentially promote inhibitory
and excitatory synapse formation&s_comma; suggesting that NLs can
discriminate between different types of presynapses. NLs have one
transmembrane region and bind to presynaptically localized neurexins
(Nrxns) through extracellular cholinesterase homology domains.
Intracellularly&s_comma; NLs have a PDZ domain binding C-terminal sequence
that binds to scaffolding proteins&s_comma; such as PSD-95&s_comma; and Shank. We
have focused on two NL isoforms&s_comma; NL1 and NL2&s_comma; and tested their role
in the regulation of excitatory and inhibitory synaptic transmission.
We overexpressed NLs or suppressed the expression of endogenous NLs
by RNAi in CA1 hippocampal pyramidal cells in rat organotypic slice
cultures. Simultaneous electrophysiological recordings were made from
transfected and neighboring untrasnsfected neurons. Overexpression of
either NL1 or NL2 enhanced excitatory synaptic transmission&s_comma; but only
NL2 increased GABAAR-mediated inhibitory synaptic transmission. We
demonstrated that the effects of both NLs on synaptic transmission
were dependent on their extracellular domains by testing chimeric NLs
and alternative splice variants of NLs. One plausible idea is that
there are Nrxns specifically expressed in the presynaptic terminal of
inihibitory neurons that only bind NL2. In other words&s_comma; differential
interactions between NLs and nrxns may underlie the difference in the
effects of the NLs on synaptic transmission. To test this hypothesis&s_comma;
we used single-cell quantitative RT-PCR and identified Nrxn isoforms
that are expressed in a cell-type specific manner in interneurons
versus excitatory neurons of hippocampus.

Host:Toshiya Manabe (Division of Neuronal Network)&s_comma;
Sumiko Watanabe (Division of Molecular and Developmental Biology)

***
Sumiko Watanabe
Inst.Med.Sci&s_comma; University of Tokyo



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