A similar impairment in CA3 mossy fibre LTP in the R6/2 mouse model of Huntington's disease and in the complexin II knockout mouse.

Abstract

Complexin II is reduced in Huntington's disease (HD) patients and in the R6/2 mouse model of HD. Mice lacking complexin II (Cplx2-/- mice) show selective cognitive deficits that reflect those seen in R6/2 mice. To determine whether or not there is a common mechanism that might underlie the cognitive deficits, long-term potentiation (LTP) was examined in the CA3 region of hippocampal slices from R6/2 mice and Cplx2-/- mice. While associational/commissural (A/C) LTP was not significantly different, mossy fibre (MF) LTP was significantly reduced in slices from R6/2 mice and Cplx2-/- mice compared with wild-type (WT) and Cplx2+/+ control mice. MF field excitatory postsynaptic potentials (fEPSPs) in response to paired stimuli were not significantly different between control mice and R6/2 or Cplx2-/- mice, suggesting that MF basal glutamate release is unaffected. Forskolin (30 microm) caused an increase in glutamate release at MF synapses in slices from R6/2 mice and from Cplx2-/- mice that was not significantly different from that seen in control mice, indicating that the capacity for increased glutamate release is not diminished. Thus, R6/2 mice and Cplx2-/- mice have a common selective impairment of MF LTP in the CA3 region. Together, these data suggest that complexin II is required for MF LTP, and that depletion of complexin II causes a selective impairment in MF LTP in the CA3 region. This impairment in MF LTP could contribute to spatial learning deficits observed in R6/2 and Cplx2-/- mice.

• Authors: Helen E Gibson, Kerstin Reim, Nils Brose, A Jennifer Morton, Susan Jones
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 22 Issue 7 Pg. 1701-12 (Oct 2005) ISSN: 0953-816X [Print] France
• PMID: 16197510 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Vesicular Transport
• Anticonvulsants
• Cyclopropanes
• Excitatory Amino Acid Antagonists
• Nerve Tissue Proteins
• complexin II
• 2-(2,3-dicarboxycyclopropyl)glycine
• Colforsin
• 2-Amino-5-phosphonovalerate
• Glycine

Topics

• 2-Amino-5-phosphonovalerate (pharmacology)
• Adaptor Proteins, Vesicular Transport
• Age Factors
• Animals
• Anticonvulsants (pharmacology)
• Colforsin (pharmacology)
• Cyclopropanes (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Dose-Response Relationship, Radiation
• Drug Interactions
• Electric Stimulation (methods)
• Excitatory Amino Acid Antagonists (pharmacology)
• Excitatory Postsynaptic Potentials (physiology, radiation effects)
• Glycine (analogs & derivatives, pharmacology)
• Hippocampus (pathology)
• Huntington Disease (genetics, pathology, physiopathology)
• In Vitro Techniques
• Long-Term Potentiation (genetics, physiology)
• Mice
• Mice, Knockout
• Mossy Fibers, Hippocampal (drug effects, physiopathology, radiation effects)
• Nerve Tissue Proteins (deficiency, genetics, physiology)
• Patch-Clamp Techniques (methods)
• Time Factors