
GABAergic synaptic scaling acts as a homeostatic mechanism to control neuronal spiking activity, in contrast to AMPAergic synaptic scaling which is not directly triggered by changes in spiking.


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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 found that perturbations which increased or decreased spiking in cortical cultures triggered multiplicative GABAergic upscaling and downscaling, respectively. In contrast, we found that changes in AMPAR or GABAR transmission only influence GABAergic scaling through their indirect effect on spiking. We propose that GABAergic scaling represents a stronger candidate for spike rate homeostat than AMPAergic scaling.

Significance Statement The nervous system maintains excitability in order to perform network behaviors when called upon to do so. Networks are thought to maintain spiking levels through homeostatic synaptic scaling, where compensatory multiplicative changes in synaptic strength are observed following alterations in cellular spike rate. Although we demonstrated that AMPAergic synaptic scaling does not appear meet these criteria as a spike rate homeostat, we now show that GABAergic scaling could play this role. Here we present evidence that the characteristics of GABAergic scaling place it in an excellent position to be a spiking homeostat. This work highlights the importance of inhibitory circuitry in the homeostatic control of excitability. Further, it provides a point of focus into neurodevelopmental disorders where excitability is impaired.

### Competing Interest Statement

The authors have declared no competing interest.

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

homeostatic-gabaergic-synaptic-scaling-is-triggered-by-changes-in-spiking-activity-not-neurotransmitter-receptor-activation


Homeostatic GABAergic Synaptic Scaling is Triggered by Changes in Spiking Activity, Not Neurotransmitter Receptor Activation
