The Role of the GABAAR α1 Subunit in Ocular Dominance Plasticity

The sensitive period of ocular dominance (OD) plasticity in the mouse visual cortex occurs around week 4-5 of development. When one eye is closed for a prolonged time during this period, the cortex will become more responsive to the open eye. This shift in ocular dominance is less pronounced before and after the sensitive period. Timing of the sensitive period is regulated by the maturation of perisomatic GABAergic inhibitory synapses formed by parvalbumin (PV) positive neurons. These synapses are formed both on excitatory and inhibitory neurons and preferentially utilize α1 subunit-containing GABAA receptors. Previous literature has shown that an early sensitive period can be induced by stimulating α1 subunit containing GABAARs with benzodiazepines, while this is not possible if the α1 subunit is rendered insensitive to benzodiazepines. The α1 subunit may thus be essential in the sensitive period plasticity of the visual cortex. We tested this by making use of α1 subunit deficient animals. We found that in these mice, expression of the α3 subunit of the GABAA receptor is increased in the visual cortex. PV positive inhibitory innervation of layer IIIII pyramidal cells is still present in α1 KO mice, and the number of perisomatic puncta is equal to that in WT mice. This was also true for perisomatic inhibition onto PV positive soma, as assessed with synaptotagmin 2 (Syt2) labeling. Also the developmental increase of visual acuity from P22 to P28 in α1 KO mice is normal which suggests unaffected timing of the sensitive period. With in vivo intrinsic optical imaging (IOI), we measured ocular dominance plasticity in the cortex of α1 subunit deficient animals. We found that in the absence of the α1 subunit OD plasticity can be induced but is reduced. Our data suggest that the α3 subunit can substitute for the α1 subunit for initiating sensitive period onset. However, specific properties of the α1 subunit could be essential for more effective plasticity. We further investigated the role of the α1 subunit in specific synapses in the inhibitory circuitry using the Cre-Lox system, during the preand normal sensitive period.