Figure 2. Accurate restoration of cellular activity through homeostatic signaling.

A) Sample traces from cortical pyramidal neurons from wild type and Kv4.2 knockout mice (Nerbonne et al., 2008, data from figure 8 therein). The knockout mice lack the Kv4.2 protein and current. Although acute pharmacological inhibition severely potentiates neuronal excitability, homeostatic rebalancing of potassium channel expression accurately restores firing properties to wild type levels. B) Data are shown for recordings made at the Drosophila NMJ. Presynaptic release (quantal content) is plotted against spontaneous miniature amplitudes (mEPSP). Each data point is average data from a single NMJ from control NMJ (open black) or NMJ to which philanthotoxin 433 (PhTX) was applied for 10min prior to recording (open red). The line represents ideal homeostatic compensation where any change in mEPSP is offset by an identical percent change in quantal content. The modulation of presynaptic release accurately offsets a broad range of postsynaptic perturbation. C) Data are presented for the Drosophila NMJ plotting excitatory postsynaptic current (EPSC) amplitude versus extracellular calcium concentration. Larvae treated with PhTx (wt + PhTX) accurately retarget control (wt) EPSC amplitudes across an order of magnitude change in extracellular calcium. Animals harboring a loss of function mutation in rim show reduced EPSCs at all calcium concentrations. Application of PhTX to rim mutant larvae demonstrates a failure of homeostatic compensation at all calcium concentrations (Muller et al., 2012). D) Intracellular recordings from a stomatogastric neuron in the intact ganglion (control), following removal of the ganglion and placement in organ culture for 10 minutes (Decentralized) and after four days in culture (4 days). After 4 days, the firing properties of the identified neuron are remarkably similar to that observed in the intact animal. Scale bars 1 sec / 10mV. Data modified from Khorkova and Golowasch, 2007. E) Example traces from Xenopus central neurons including control and a neuron expressing transgenic Kir2.1 (Pratt et al., 2007). Expression of Kir2.1 induces a change in the underlying current densities including the sodium current (quantified at right) that help sustain firing properties at control levels.