Effects of Diazepam on Low-Frequency and High-Frequency Electrocortical γ-Power Mediated by α1- and α2-GABA_A Receptors

Round 1

Reviewer 1 Report

 

 

 

This is a clearly written and well illustrated paper that reports on the effects of targeted knockouts of different GABAA receptor subtypes on the effects of benezodiazepines.  Interesting findings are reported for the differential involvement of these receptor subtypes in benezodiazepine effects on EEG and neuronal discharge.  These results further establish the selectivity of GABAergic agents and point the way to further characterization of these important inhibitory receptors.  I have only a couple of minor issues:

 

“largely independent on their molecular mechanism”  should be: largely independent of their molecular mechanism

 

“It is worth to mention that Kopp” should be: It is worth mentioning that Kopp

 

 

“GABAA receptors in vivo”  should be: GABAA receptors in vivo.

 

 

“Our experiments monitor cortical activity” should be: Our experiments monitored cortical activity

 

 

“receptor subtypes possibly contribute to the” should be: receptor subtypes likely contribute to the

 

 

 

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

In this manuscript, the authors reveal the action of diazepam produced by a single subtype of the GABA_A receptor using mice carrying knock-in mutation especially in a1-DZa1 & a2- DZa2 mice. This is based on the idea that these points mutation do not compromise the physiological function of GABA_A receptors but difference develops only in the presence of benzodiazepines. They use diazepam to test this idea in mutant mice and observed that diazepam reduced spontaneous action potential firing of cortical neurons via both, a1- and a2-GABA_A receptors but enhancement of spectral power in the low g-range and intra-cortical synchrony were observed in wild type and DZa2 but not in DZa1-mice. Understanding the role of the subpopulation of GABA_A receptor on circuit pharmacology is important and this data adds to significant literature on the subject. I would recommend this research article for publication.

Author Response

Please see the attachment

Author Response File: Author Response.docx