Increased network excitability and impaired induction of long-term potentiation in the dentate gyrus of collybistin-deficient mice in vivo.
Collybistin (Cb), a brain-specific guanine nucleotide exchange factor, has been shown to be essential for the gephyrin-dependent clustering of a specific set of GABA(A) receptors at inhibitory postsynaptic sites. Here, we examined whether the lack of Cb affects synaptic properties and neuronal activity in the intact hippocampus by monitoring network activity in the dentate gyrus of Cb-deficient mice after perforant-path stimulation in vivo. We found a decreased threshold for evoked population spikes of granule cells, indicating their increased excitability. Paired-pulse inhibition of the population spike, a measure for somatic GABAergic network inhibition, was enhanced. Mutant mice exhibited steeper slopes of field excitatory postsynaptic potentials, consistent with a reduced dendritic inhibition. In addition, the induction of long-term potentiation (LTP) was reduced. In line with these functional changes, the number of postsynaptic gephyrin and GABA(A) receptor clusters in the Cb-deficient dentate gyrus was significantly decreased. In conclusion, our data provide the first evidence that Cb-deficiency leads to significant changes of GABAergic inhibition, network excitability and synaptic plasticity in vivo.
Jedlicka
Peter
P
Institute of Clinical Neuroanatomy, Goethe University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. jedlicka@em.uni-frankfurt.de
Papadopoulos
Theofilos
T
Deller
Thomas
T
Betz
Heinrich
H
Schwarzacher
Stephan W
SW
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D004558:Electric Stimulation; D004594:Electrophysiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D019580:Perforant Pathway / Q000166:cytology / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
C577403:Arhgef9 protein, mouse; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D064067:Rho Guanine Nucleotide Exchange Factors; C073441:gephyrin