Article

Homeostatic plasticity mechanisms are required for juvenile, but not adult, ocular dominance plasticity

School of Biosciences and the Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff CF10 3AX, United Kingdom.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 01/2012; 109(4):1311-6. DOI: 10.1073/pnas.1112204109
Source: PubMed

ABSTRACT Ocular dominance (OD) plasticity in the visual cortex is a classic model system for understanding developmental plasticity, but the visual cortex also shows plasticity in adulthood. Whether the plasticity mechanisms are similar or different at the two ages is not clear. Several plasticity mechanisms operate during development, including homeostatic plasticity, which acts to maintain the total excitatory drive to a neuron. In agreement with this idea, we found that an often-studied substrain of C57BL/6 mice, C57BL/6JOlaHsd (6JOla), lacks both the homeostatic component of OD plasticity as assessed by intrinsic signal imaging and synaptic scaling of mEPSC amplitudes after a short period of dark exposure during the critical period, whereas another substrain, C57BL/6J (6J), exhibits both plasticity processes. However, in adult mice, OD plasticity was identical in the 6JOla and 6J substrains, suggesting that adult plasticity occurs by a different mechanism. Consistent with this interpretation, adult OD plasticity was normal in TNFα knockout mice, which are known to lack juvenile synaptic scaling and the homeostatic component of OD plasticity, but was absent in adult α-calcium/calmodulin-dependent protein kinase II;T286A (αCaMKII(T286A)) mice, which have a point mutation that prevents autophosphorylation of αCaMKII. We conclude that increased responsiveness to open-eye stimulation after monocular deprivation during the critical period is a homeostatic process that depends mechanistically on synaptic scaling during the critical period, whereas in adult mice it is mediated by a different mechanism that requires αCaMKII autophosphorylation. Thus, our study reveals a transition between homeostatic and long-term potentiation-like plasticity mechanisms with increasing age.

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    • "Reversal of short-and long-term plasticity or short-and long-term memory typically results in the reversal of synaptic strengths or behavior toward prestimulus levels. This reversal of synaptic strength toward earlier baselines is likely to be the outcome of hierarchic and constitutive cellular processes initiated during development and consolidated in early postnatal life that defines a basal level of circuit function that is subsequently coexpressed with additional cellular processes that regulate bidirectional changes in this set point of circuit function to accommodate environmental contingencies in the form of learning and memory (Hubel and Wiesel 1970; Desai et al. 2002; Turrigiano and Nelson 2004; Huupponen et al. 2007; Petrus et al. 2011; Ransom et al. 2012). Disruptions of the cellular processes associated with the activity/experience-dependent change in function might allow the initial constitutive homeostatic processes to restore synaptic strengths to previous levels. "
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    • "Discovery of BCM-like regulation of visual responses in humans is important since homeostatic phenomena and metaplasticity are believed to underlie the ability of cortical networks to maintain stable function in the face of developmental or learning-induced changes in drive. Metaplasticity could play a role in circuit rearrangements triggered in the visual cortex by alterations in sensory input, as suggested by previous animal studies (Ranson et al. 2012). Metaplasticity could also be crucial for the process of plasticity in the adult, healthy visual system; it is known that adult visual cortex retains a surprisingly high degree of plasticity fundamental in reaction to sensory loss (Sabel 2008; Lunghi et al. 2011). "
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    • "Other mechanisms of critical period ODP are not shared with adult ODP. For instance, adult TNFa-knockout mice that lack homeostatic scaling in vitro had normal increases in open-eye responses following MD while adult aCaMKII;T286A mice, which have a point mutation that prevents autophosphorylation of aCaMKII, lacked the strengthening of open-eye responses following MD (Ranson et al., 2012). Further evaluation of the shared and distinct molecular mechanisms between critical period and adult ODP may reveal the factors that account for the decline in plasticity with age. "
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