Homeostatic plasticity refers to the mechanisms that a cell or network are thought to employ, in order to homeostatically maintain a set level of spiking activity. Such a process would be critical for ensuring that networks do not become too active or inactive. Homeostatic plasticity is studied by perturbing activity levels and identifying mechanisms that could contribute to the restoration of the original activity levels. These mechanisms include compensatory changes in excitatory and inhibitory synaptic strength, as well as changes in intrinsic cellular excitability. For instance, when spiking activity was blocked for 2 days in cultured neural networks, glutamatergic synaptic strength increased and GABAergic synaptic strength decreased. Homeostatic plasticity is typically studied in vitro at a stage when GABA or glycine are inhibitory. I will discuss the expression of homeostatic plasticity in the living embryonic spinal cord at an early developmental stage when both glutamate and GABA are depolarizing and excitatory. When spiking activity is blocked for 2 days in the living embryo, compensatory increases in excitatory GABAergic and glutamatergic synaptic strength are observed. Interestingly, GABAergic synaptic strength is increased through dramatic increases in intracellular chloride, thereby enhancing the driving force for these chloride-mediated currents. We are currently working to understand how this occurs. Not only are the compensatory changes in GABAergic synaptic strength mediated by changes in chloride levels, but it appears that the chloride-mediated GABAergic currents are involved in triggering homeostatic plasticity. When GABAa receptors were blocked in the embryo for 2 days, increases in GABAergic and glutamatergic synaptic strength were observed, and were even larger than following activity blockade. GABAergic synaptic strength was again increased through chloride accumulation. We believe that activity blockade reduces the release of GABA, thereby reducing GABAa receptor activation, which then triggers changes in GABAergic and glutamatergic synaptic strength. This places the GABAa receptor, and possibly the depolarizing chloride current, as part of the sensing machinery that triggers homeostatic plasticity.