Altered Hippocampal Response to Systemic Administration of an α5 type GABA-A Receptor Modulator in a Rat Model of Alzheimer’s disease

α5 subunit containing GABA type A receptors (a5GABAARs) are highly expressed in the hippocampus of humans and animals. The functioning of these receptors is altered in neurodevelopmental disorders including autism and by neuroinflammation and injuries to the brain (reviewed by Jacobs 2019).  Ratner and colleagues (Heliyon, 2021) show for the first time that systemic administration of a5IA, a selective negative modulator of a5GABAARs, increases peak ripple amplitudes in wild type adult rats but has no effect on peak ripple amplitudes in the TgF344-AD rat model of Alzheimer's disease which also shows elevated plasma concentrations of AB42 and AB40 during the prodromal state of the disease when memory function is still intact.  These findings demonstrate the selective sensitivity of the healthy versus diseased hippocampus to chemicals that modulate inhibitory neurotransmission.  These findings also indicate that tonic inhibitory neurotransmission is altered in this highly translational rat model of Alzheimer's disease. 

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