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Publication : Developmental Disruption of GABA<sub>A</sub>R-Meditated Inhibition in Cntnap2 KO Mice.

First Author  Bridi MS Year  2017
Journal  eNeuro Volume  4
Issue  5 PubMed ID  28966979
Mgi Jnum  J:255293 Mgi Id  MGI:6114325
Doi  10.1523/ENEURO.0162-17.2017 Citation  Bridi MS, et al. (2017) Developmental Disruption of GABAAR-Meditated Inhibition in Cntnap2 KO Mice. eNeuro 4(5):ENEURO.0162-17.2017
abstractText  GABA released from presynaptic sites induces short-lived phasic inhibition mediated by synaptic GABAA receptors (GABAARs) and longer-duration tonic inhibition mediated by extrasynaptic GABAA or GABAB receptors (GABABRs). A number of studies have found that contactin-associated protein 2 (Cntnap2) knockout (KO) mice, a well-established mouse model of autism, exhibit reduced interneuron numbers and aberrant phasic inhibition. However, little is known about whether tonic inhibition is disrupted in Cntnap2 KO mice and when the disruption of inhibition begins to occur during postnatal development. We examined tonic and phasic inhibition in layer 2/3 pyramidal cells of primary visual cortex of Cntnap2 KO at two different developmental stages, three to four and six to eight weeks of age. We found that both phasic inhibition and GABAAR but not GABABR-mediated tonic inhibition was reduced in pyramidal cells from six- to eight-week-old Cntnap2 KO mice, while in three- to four-week-old mice, no significant effects of genotype on tonic or phasic inhibition was observed. We further found that activation of tonic currents mediated by delta-subunit-containing GABAARs reduced neural excitability, an effect that was attenuated by loss of Cntnap2. While the relative contribution of tonic versus phasic inhibition to autism-related symptoms remains unclear, our data suggest that reduced tonic inhibition may play an important role, and delta-subunit-containing GABAARs may be a useful target for therapeutic intervention in autism.
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