Temporal regulation of the expression locus of homeostatic plasticity

Department of Biology and Center for Complex Systems, Brandeis University, Waltham, MA 02454, USA.
Journal of Neurophysiology (Impact Factor: 2.89). 10/2006; 96(4):2127-33. DOI: 10.1152/jn.00107.2006
Source: PubMed


Homeostatic plasticity of excitatory synapses plays an important role in stabilizing neuronal activity, but the mechanism of this form of plasticity is incompletely understood. In particular, whether the locus of expression is presynaptic or postsynaptic has been controversial. Here we show that the expression locus depends on the time neurons have spent in vitro. In visual cortical cultures < or =14 days in vitro (DIV), 2 days of TTX treatment induced an increase in miniature excitatory postsynaptic current (mEPSC) amplitude onto pyramidal neurons, without affecting mEPSC frequency. However, in cultures > or =18 DIV, the same TTX treatment induced a large increase in mEPSC frequency, whereas the amplitude effect was reduced. The increased mEPSC frequency was associated with an increased density of excitatory synapses and increased presynaptic vesicle release in response to electrical stimulation. This indicates a shift from a predominantly postsynaptic response to TTX in < or =14 DIV cultures, to a coordinated pre- and postsynaptic response in > or =18 DIV cultures. This shift was not specific for cortical cultures because a similar shift was observed in cultured hippocampal neurons. Culturing neurons from older animals showed that the timing of the switch depends on the time the neurons have spent in vitro, rather than their postnatal age. This temporal switch in expression locus can largely reconcile the contradictory literature on the expression locus of homeostatic excitatory synaptic plasticity in central neurons. Furthermore, our results raise the intriguing possibility that the expression mechanism of homeostatic plasticity can be tailored to the needs of the network during different stages of development or in response to different challenges to network function.

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Available from: Corette J Wierenga, Jul 01, 2014
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    • "Whether presynaptic modifications accompany postsynaptic ones may depend on developmental age. Wierenga et al. (2006) found that, in young cultures (<2 weeks in vitro), scaling was exclusively postsynaptic in origin but that, in older cultures, scaling included both presynaptic and postsynaptic elements. A different set of studies, using hippocampal cultures, suggested that presynaptic/postsynaptic scaling may involve different physical mechanisms than postsynaptic-only scaling (Thiagarajan et al. 2005; Lindskog et al., 2010; Groth et al., 2011). "

    Homeostatic Control of Brain Function, Edited by Detlev Boison and Susan Masino, 01/2015; Oxford University Press.
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    • "In developing neurons, a form of HSP called synaptic scaling has been described in which a uniform, global multiplicative change occurs in all excitatory synapses (Turrigiano et al., 1998), thereby preserving relative synaptic weights (Turrigiano and Nelson, 2000). In older neurons, however, homeostatic changes at excitatory synapses do not seem to occur by multiplicative scaling (Burrone et al., 2002; Echegoyen et al., 2007; Goel and Lee, 2007; Thiagarajan et al., 2005; Wierenga et al., 2006). This developmental switch suggests the existence of an alternate, unidentified mechanism for the coexistence of homeostatic and associative plasticity in the adult brain. "
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    • "In mature hippocampal and cortical cultures, postsynaptic receptor blockade increases mEPSC frequency (Burrone et al., 2002; Thiagarajan et al., 2005; Wierenga et al., 2006) and augments presynaptic terminal size and release probability (Murthy et al., 2001; Thiagarajan et al., 2005). By contrast, local stimulation of dendrites acutely reduces release probability of contacting presynaptic terminals (Branco et al., 2008). "
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