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: 9.67). 01/2012; 109(4):1311-6. DOI: 10.1073/pnas.1112204109
Source: PubMed


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.

Download full-text


Available from: Claire E J Cheetham,
  • Source
    • "After 10 days of deprivation, RS neurons showed a remarkable rebound potentiation back to control values despite the continued deprivation (Figure 2B, q = 1.527, p > 0.05 neither spared nor deprived significantly different from control, ANOVA with Tukey's post hoc). The rebound potentiation in RS cells and its time course are reminiscent of the homeostatic rebound potentiation reported previously for deprived eye responses in visual cortex (Kaneko et al., 2008; Ranson et al., 2012). Neither the original depression nor the rebound potentiation were input specific, affecting spared and deprived inputs alike (Figure 2A). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Layer 5 contains the major projection neurons of the neocortex and is composed of two major cell types: regular spiking (RS) cells, which have cortico-cortical projections, and intrinsic bursting cells (IB), which have subcortical projections. Little is known about the plasticity processes and specifically the molecular mechanisms by which these two cell classes develop and maintain their unique integrative properties. In this study, we find that RS and IB cells show fundementally different experience-dependent plasticity processes and integrate Hebbian and homeostatic components of plasticity differently. Both RS and IB cells showed TNFα-dependent homeostatic plasticity in response to sensory deprivation, but IB cells were capable of a much faster synaptic depression and homeostatic rebound than RS cells. Only IB cells showed input-specific potentiation that depended on CaMKII autophosphorylation. Our findings demonstrate that plasticity mechanisms are not uniform within the neocortex, even within a cortical layer, but are specialized within subcircuits.
    Neuron 10/2015; DOI:10.1016/j.neuron.2015.09.025 · 15.05 Impact Factor
  • Source
    • "Assuming the SSVEP response is a valid reflection of neural contrast responses, the present results, based on measures at three target contrast levels, suggest the sensitivity improvement of the patched eye due to short term patching could be a consequence of an increase in contrast-gain (or a reduction of suppression) and/or a reduction in neural noise. Such a change in the balance of excitation and suppression associated with binocular combination (Meese et al., 2006) is in good agreement with the idea of homeostatic intrinsic plasticity (Desai et al., 1999; Mrsic-Flogel et al., 2007; Ranson et al., 2012), for review, see (Turrigiano, 2011). In particular, it is possible that during the patching stage when neural responses corresponding to the patched eye's contribution to binocular combination are much reduced, neurons might respond by regulating their intrinsic properties to shift their input/output function to the left (increase the contrast gain or decrease interocular inhibition) in an effort to strengthen the patched eye's contribution to the binocular percept. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Several recent studies have demonstrated that following short-term monocular deprivation in normal adults, the patched eye, rather than the unpatched eye, becomes stronger in subsequent binocular viewing. However, little is known about the site and nature of the underlying processes. In this study, we examine the underlying mechanisms by measuring steady-state visual evoked potentials (SSVEPs) as an index of the neural contrast response in early visual areas. Methods: The experiment consisted of three consecutive stages: a pre-patching EEG recording (14 minutes), a monocular patching stage (2.5 hours) and a post-patching EEG recording (14 minutes; started immediately after the removal of the patch). During the patching stage, a diffuser (transmits light but not pattern) was placed in front of one randomly selected eye. During the EEG recording stage, contrast response functions for each eye were measured. Results: The neural responses from the patched eye increased after the removal of the patch, whilst the responses from the unpatched eye remained the same. Such phenomena occurred under both monocular and dichoptic viewing conditions. Conclusions: We interpret this eye dominance plasticity in adult human visual cortex as homeostatic intrinsic plasticity regulated by an increase of contrast-gain in the patched eye.
    Restorative neurology and neuroscience 06/2015; 33(3):381-387. DOI:10.3233/RNN-140472 · 2.49 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: An important cellular mechanism contributing to the strength and duration of memories is activity-dependent alterations in the strength of synaptic connections within the neural circuit encoding the memory. Reversal of the memory is typically correlated with a reversal of the cellular changes to levels expressed prior to the stimulation. Thus, for stimulus-induced changes in synapse strength and their reversals to be functionally relevant, cellular mechanisms must regulate and maintain synapse strength both prior to and after the stimuli inducing learning and memory. The strengths of synapses within a neural circuit at any given moment are determined by cellular and molecular processes initiated during development and those subsequently regulated by the history of direct activation of the neural circuit and system-wide stimuli such as stress or motivational state. The cumulative actions of stimuli and other factors on an already modified neural circuit are attenuated by homeostatic mechanisms that prevent changes in overall synaptic inputs and excitability above or below specific set points (synaptic scaling). The mechanisms mediating synaptic scaling prevent potential excitotoxic alterations in the circuit but also may attenuate additional cellular changes required for learning and memory, thereby apparently limiting information storage. What cellular and molecular processes control synaptic strengths before and after experience/activity and its reversals? In this review we will explore the synapse-, whole cell-, and circuit level-specific processes that contribute to an overall zero sum-like set of changes and long-term maintenance of synapse strengths as a consequence of the accommodative interactions between long-term synaptic plasticity and homeostasis.
    Learning & memory (Cold Spring Harbor, N.Y.) 02/2014; 21(3):128-34. DOI:10.1101/lm.027326.112 · 3.66 Impact Factor
Show more