A related phenomenon has been revealed in animals harboring mutations in genes that encode ion channels. Several studies provide evidence that deleting an ion channel gene invokes compensatory changes in the expression of other ion channels in both invertebrate and mammalian systems (MacLean et al., 2003, Swensen and Bean, 2005, Muraro et al., 2008, Andrásfalvy et al., 2008, Nerbonne et al., 2008, Van Wart and

Matthews, 2006 and Bergquist et al., 2010). In many cases, ion channel expression is rebalanced and cell-type-specific firing properties are restored (Figure 2). One conclusion is that homeostatic signaling systems enable a neuron to compensate for the absence of an ionic current and re-establish cell-type-specific firing properties through altered expression of other ion channels. A second conclusion is that ion channel expression is not a fixed parameter selleck kinase inhibitor associated with cell fate. Rather, a given cell type can maintain characteristic firing properties using different combinations of ion channel densities. The homeostatic rebalancing of ion channel expression is astonishing, in part, because of its staggering complexity (Marder and Prinz, 2002). There can be thousands of synaptic inputs and dozens of different

channels controlling the Hydroxychloroquine cost firing properties of an individual cell. The molecular mechanisms that achieve the homeostatic rebalancing of ion channel expression remain virtually unknown (but see Muraro also et al., 2008, Driscoll et al., 2013, Temporal

et al., 2012 and Khorkova and Golowasch, 2007). Synaptic scaling was revealed by experiments examining the effects of chronic activity suppression in cultured mammalian neurons (Turrigiano et al., 1998 and O’Brien et al., 1998). It is now clear, both in vitro and in vivo, that chronic manipulation of neural activity drives counteracting changes in neurotransmitter receptor abundance that help to restore neural activity to baseline levels (Thiagarajan et al., 2005, Zhao et al., 2011, Garcia-Bereguiain et al., 2013, Mrsic-Flogel et al., 2007, Echegoyen et al., 2007, Deeg and Aizenman, 2011, Gainey et al., 2009, Keck et al., 2013 and Hengen et al., 2013; see also Tyagarajan and Fritschy, 2010). The bidirectional modulation of neurotransmitter receptor abundance was initially termed “synaptic scaling” because the measured amplitudes of spontaneous miniature release events are modified in a multiplicative manner, presumably through proportional changes in receptor abundance at every individual synapse (Turrigiano et al., 1998 and Turrigiano, 2011; see also Kim and Tsien, 2008). This effect has the property of preserving the relative differences in efficacy among the numerous synapses on a single postsynaptic target. Because of this, it has been proposed that synaptic scaling stabilizes neuronal excitability while preserving learning-related information contained in relative synaptic weights.