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

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.

Fig. 1.

In vivo intrinsic signal imaging reveals the absence of the homeostatic component of OD plasticity during the critical period in the 6JOla substrain. (A) Schematic of the intrinsic signal imaging setup. (B) Deprivation and imaging timeline. (C) Representative retinotopic maps from the two C57BL/6 substrains investigated overlaid over the cortical vasculature. (Scale bar: 1 mm.) (D) Binocular zone responsiveness to closed-eye stimulation during MD. (E) Binocular zone responsiveness to open-eye stimulation during MD. (F) Monocular zone responsiveness to closed-eye stimulation during MD. (G) ODI in the binocular zone during MD. For 6J: control, n = 10; 3 d MD, n = 8; 5–6 d MD, n = 9. For 6JOla: control, n = 22; 3 d MD, n = 6; 5–6 d MD, n = 11. **P < 0.01; *P < 0.05 for comparisons between time points. In D–F, response values are mean ΔR/R normalized to control values ± SEM.

Fig. 2.

Ex vivo homeostatic synaptic scaling is absent in 6JOla mice. (A) Example traces showing mEPSCs recorded in brain slices from 6J and 6JOla control (CTRL) and dark-exposed (DE) mice. (Scale bars: 10 pA; 200 ms.) (B) Effect of DE on mEPSC amplitude. Data are shown as mean for each mouse (small symbols) and grand mean ± SEM (large symbols); n = 6 mice/group. **P < 0.01 for 6J DE vs. all other groups. (C) Effect of DE on mEPSC rise time. Symbols are as in B. (D) Effect of DE on mEPSC frequency. Symbols are as in B. (E) Cumulative distribution plot of mean mEPSC amplitude for individual neurons in the four groups. 6J control, n = 27; 6J DE, n = 25; 6JOla control, n = 20; 6JOla DE, n = 21. (F) Cumulative distribution plot showing the effect of DE on raw mEPSC amplitude for 6J mice. n = 50 mEPSCs/neuron. mEPSCs >30 pA are not shown. (G) As in F for 6JOla mice.

Fig. 3.

Adult OD plasticity is normal in 6JOla and TNFα^−/− mice but absent in T286A mice. (A) Adult deprivation and imaging timeline. (B) ODI shift after 7 d of MD. (C) Responsiveness to closed-eye (Left) and open-eye (Right) stimulation before and after 7 d of MD. For 6J and 6JOla control and 7 d MD, n = 6; T286A control, n = 5; 7 d MD, n = 6; TNFα^−/− control, n = 5; 7 d control, n = 5; 7 d MD, n = 6. **P < 0.01; *P < 0.05. Response values are mean ΔR/R normalized to control values ± SEM. Gray box indicates control 6J mean ± SEM.