Mice Lacking the Major Adult GABAA Receptor Subtype Have Normal Number of Synapses, But Retain Juvenile IPSC Kinetics Until Adulthood

• Published in: Journal of neurophysiology 2005-07, Vol.94 (1), p.338
• Main Authors: Bosman, Laurens W. J, Heinen, Klaartje, Spijker, Sabine, Brussaard, Arjen B
• Format: Article
• Language: English
• Subjects: Age Factors; Anesthetics, Local - pharmacology; Animals; Carrier Proteins - genetics; Carrier Proteins - metabolism; Electric Stimulation - methods; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Inhibition - physiology; Neurons - physiology; Neurons - radiation effects; Patch-Clamp Techniques - methods; Receptors, GABA-A - deficiency; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; Synapses - physiology; Synaptic Transmission - physiology; Tetrodotoxin - pharmacology; Visual Cortex - cytology; Visual Cortex - growth & development; Visual Cortex - radiation effects
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00084.2005

1 Departments of Experimental Neurophysiology and 2 Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands Submitted 24 January 2005; accepted in final form 6 March 2005 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 1 subunit replaces the 2 and/or 3 subunit as major 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 1 subunit. We show that 1 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, 1 already affects GABAergic transmission in the neonatal cerebral cortex when it is only sparsely expressed. It appears that the 1 –/– 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. Address for reprint requests and other correspondence: A. B. Brussaard, Dept. of Experimental Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands (E-mail: brssrd{at}cncr.vu.nl )