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.

Homeostatic plasticity and synaptic scaling in the adult mouse auditory cortex

“…2A,D). This result is consistent with previous studies in V1 demonstrating an adjustment of visually evoked responses after prolonged visual deprivation due to homeostatic mechanisms 10,45 . Likewise, SNHL led to an increased excitability of A1 layers 2/3 neurons in A1 slices of juvenile animals 12 .…”

“…Since it has been described that the commonly used C57BL/6 JOlaHsd mice lack homeostatic synaptic scaling 45 , we did not use mice of this strain. C57BL/6J (Jackson labs), which are shown to display synaptic scaling 45 and TNFαKO mice (shown to lack synaptic scaling in vivo 10 ) were raised in standard cages on a 12 h light/ dark cycle, with food and water available ad libitum. Animal housing in our institution is regularly supervised by veterinaries from the state of Thuringia, Germany.…”

Integrating Hebbian and homeostatic plasticity: the current state of the field and future research directions

“…Many studies have confirmed this original result in vitro [6], as well as ex vivo in acute slices prepared from both juvenile and adult animals that had previously undergone in vivo deprivation [7][8][9][10][11][12][13][14]. Synaptic scaling does have layer-specific properties in cortex, where scaling in layer 4 is limited to early development [7], but layer 5 [12,15] and layer 2/3 [10] can scale throughout adulthood.…”

Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling

“…Suggestive evidence for scaling comes from the finding that open-eye potentiation is absent in juvenile mice lacking the glial cytokine, TNF-alpha; neurons from these mice fail to show 'upscaling' following TTX treatment [53]. However, there remains the possibility of defective metaplasticity in these mice, and additional experiments have shown that open-eye potentiation in adults is normal in this and other mutants that lack scaling affects in culture [102]). …”