Highlights d Visual cortical circuits in vivo exhibit criticality, an ideal computational regime d Monocular deprivation disrupts criticality prior to firing rate depression d Criticality is actively re-established as firing rates are maximally depressed d Models suggest inhibitory plasticity as a mechanism of a stable computational regime

Immune responses are vital for bone regeneration and play an essential role in the fate of biomaterials after implantation. As a kind of plastic cell, macrophages are central regulators of the immune response during the infection and wound healing process including osteogenesis and angiogenesis. Magnesium-calcium phosphate cement (MCPC) has been reported as a promising candidate for bone repair with promoted osteogenesis both in vitro and in vivo. However, relatively little is known about the effects of MCPC on immune response and the following outcome. In this study, we investigated the interactions between macrophages and MCPC. Here we found that the pro-inflammatory cytokines including TNF-α and IL-6 were less expressed and the bone repair related cytokine of TGF-β1 was up-regulated by macrophages in MCPC extract. Furthermore, the enhanced osteogenic capacity of BMSCs and angiogenic potential of HUVECs were acquired in vitro by the MCPC-induced immune microenvironment. These findings suggest that MCPC is able to facilitate bone healing by endowing favorable osteoimmunomodulatory properties and influencing crosstalk behavior between immune cells and osteogenesis-related cells.

Mounting evidence supports the hypothesis that the cortex operates near a critical state, defined as the transition point between order (large-scale activity) and disorder (small-scale activity). This criticality is manifested by power law distribution of the size and duration of spontaneous cascades of activity, which are referred as neuronal avalanches. The existence of such neuronal avalanches has been confirmed by several studies both in vitro and in vivo, among different species and across multiple spatial scales. However, despite the prevalence of scale free activity, still very little is known concerning whether and how the scale-free nature of cortical activity is altered during external stimulation. To address this question, we performed in vivo two-photon population calcium imaging of layer 2/3 neurons in primary visual cortex of behaving mice during visual stimulation and conducted statistical analyses on the inferred spike trains. Our investigation for each mouse and condition revealed power law distributed neuronal avalanches, and irregular spiking individual neurons. Importantly, both the avalanche and the spike train properties remained largely unchanged for different stimuli, while the cross-correlation structure varied with stimuli. Our results establish that microcircuits in the visual cortex operate near the critical regime, while rearranging functional connectivity in response to varying sensory inputs.

A substantial reorganization of neural activity and neuron-to-movement relationship in motor cortical circuits accompanies the emergence of reproducible movement patterns during motor learning. Little is known about how this tempest of neural activity restructuring impacts the stability of network states in recurrent cortical circuits. To investigate this issue, we reanalyzed data in which we recorded for 14 days via population calcium imaging the activity of the same neural populations of pyramidal neurons in layer 2/3 and layer 5 of forelimb motor and pre-motor cortex in mice during the daily learning of a lever-press task. We found that motor cortex network states remained stable with respect to the critical network state during the extensive reorganization of both neural population activity and its relation to lever movement throughout learning. Specifically, layer 2/3 cortical circuits unceasingly displayed robust evidence for operating at the critical network state, a regime that maximizes information capacity and transmission, and provides a balance between network robustness and flexibility. In contrast, layer 5 circuits operated away from the critical network state for all 14 days of recording and learning. In conclusion, this result indicates that the wide-ranging malleability of synapses, neurons, and neural connectivity during learning operates within the constraint of a stable and layer-specific network state regarding dynamic criticality, and suggests that different cortical layers operate under distinct constraints because of their specialized goals.