Microglia, the brain’s resident macrophages, help to regulate brain function by removing dying neurons, pruning non-functional synapses, and producing ligands that support neuronal survival 1 . Here we show that microglia are also critical modulators of neuronal activity and associated behavioural responses in mice. Microglia respond to neuronal activation by suppressing neuronal activity, and ablation of microglia amplifies and synchronizes the activity of neurons, leading to seizures. Suppression of neuronal activation by microglia occurs in a highly region-specific fashion and depends on the ability of microglia to sense and catabolize extracellular ATP, which is released upon neuronal activation by neurons and astrocytes. ATP triggers the recruitment of microglial protrusions and is converted by the microglial ATP/ADP hydrolysing ectoenzyme CD39 into AMP; AMP is then converted into adenosine by CD73, which is expressed on microglia as well as other brain cells. Microglial sensing of ATP, the ensuing microglia-dependent production of adenosine, and the adenosine-mediated suppression of neuronal responses via the adenosine receptor A 1 R are essential for the regulation of neuronal activity and animal behaviour. Our findings suggest that this microglia-driven negative feedback mechanism operates similarly to inhibitory neurons and is essential for protecting the brain from excessive activation in health and disease.

The rapid elimination of dying neurons and nonfunctional synapses in the brain is carried out by microglia, the resident myeloid cells of the brain. Here we show that microglia clearance activity in the adult brain is regionally regulated and depends on the rate of neuronal attrition. Cerebellar, but not striatal or cortical, microglia exhibited high levels of basal clearance activity, which correlated with an elevated degree of cerebellar neuronal attrition. Exposing forebrain microglia to apoptotic cells activated gene-expression programs supporting clearance activity. We provide evidence that the polycomb repressive complex 2 (PRC2) epigenetically restricts the expression of genes that support clearance activity in striatal and cortical microglia. Loss of PRC2 leads to aberrant activation of a microglia clearance phenotype, which triggers changes in neuronal morphology and behavior. Our data highlight a key role of epigenetic mechanisms in preventing microglia-induced neuronal alterations that are frequently associated with neurodegenerative and psychiatric diseases.

The purpose of this study was to investigate the knowledge of a group of physical education (PE) teachers about the emergency management of dental trauma in Hong Kong. A postal questionnaire was sent to PE teachers in 100 randomly selected secondary schools in Hong Kong. A total of 166 teachers from 65 schools responded. Results show that a majority of the respondents have received formal teaching training (98.8%). While all but one teacher had received formal first aid training, only eight of them recalled that they had received advice on the management of dental trauma. Concerning the management of tooth fracture, 118 respondents (71.1%) gave an appropriate answer. In contrast, only 29 teachers (17.5%) were able to indicate the appropriate management for an avulsed tooth. Over 60% (102) of the respondents indicated it was "very urgent" to seek professional assistance if a permanent tooth has been avulsed, but they had little knowledge of the correct procedures for replanting or transporting avulsed teeth. Only 15 respondents (9%) pointed out that milk was the medium of choice for transporting avulsed teeth. Finally, over 90% (157) of respondents indicated that they had never received advice on the emergency procedures for the management of dental avulsion. The present study showed that the level of lay knowledge of management of dental injuries in a selection of PE teachers in Hong Kong is inadequate and educational campaigns are necessary to improve their emergency management of dental injuries.

No abstract