GABAergic synaptic scaling is triggered by changes in spiking activity rather than transmitter receptor activation

Abstract Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking. Moreover, studies examining homeostatic perturbations in vivo have suggested that GABAergic synapses may be more critical in terms of spiking homeostasis. Here we show results that GABAergic scaling can act to homeostatically control spiking levels. We find that increased or decreased spiking in cortical cultures triggers multiplicative GABAergic upscaling and downscaling, respectively. In contrast, we find that changes in AMPAR or GABAR transmission only influence GABAergic scaling through their indirect effect on spiking. We propose that GABAergic scaling, rather than glutamatergic scaling, is a key player in spike rate homeostasis.