Mice lacking the major adult GABAA receptor subtype have normal number of synapses, but retain juvenile IPSC kinetics until adulthood.
There is a large variation in structurally and functionally different GABA(A) receptor subtypes. The expression pattern of GABA(A) receptor subunits is highly regulated, both temporarily and spatially. Especially during development, profound changes in subunit expression have been described. In most brain areas, the GABA(A) receptor alpha1 subunit replaces the alpha2 and/or alpha3 subunit as major alpha subunit. This is accompanied by a marked decrease in the open time of GABA(A) receptors and hence in the duration of postsynaptic responses. We describe here the development of GABAergic, synaptic transmission in mice lacking the alpha1 subunit. We show that alpha1 is to a large extent--but not entirely--responsible for the relatively short duration of postsynaptic responses in the developing and the mature brain. However, alpha1 already affects GABAergic transmission in the neonatal cerebral cortex when it is only sparsely expressed. It appears that the alpha1 -/- mice do not show a large reduction in GABAergic synapses but do retain long-lasting postsynaptic currents into adulthood. Hence, they form a good model to study the functional role of developmental GABA(A) receptor subunit switching.
Bosman
Laurens W J
LW
Department of Experimental Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
Heinen
Klaartje
K
Spijker
Sabine
S
Brussaard
Arjen B
AB
D000367:Age Factors; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D008564:Membrane Potentials / Q000502:physiology / Q000528:radiation effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D011963:Receptors, GABA-A / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014793:Visual Cortex / Q000166:cytology / Q000254:growth & development / Q000528:radiation effects
D000779:Anesthetics, Local; D002352:Carrier Proteins; C546241:Gabra1 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C073441:gephyrin; D013779:Tetrodotoxin