Microglial control of neuronal activity

Abstract

Fine-tuning of neuronal activity was thought to be a neuron-autonomous mechanism until the discovery that astrocytes are active players of synaptic transmission. The involvement of astrocytes has changed our understanding of the roles of non-neuronal cells and shed new light on the regulation of neuronal activity. Microglial cells are the macrophages of the brain and they have been mostly investigated as immune cells. However, recent data discussed in this review support the notion that, similarly to astrocytes, microglia are involved in the regulation of neuronal activity. For instance, in most, if not all, brain pathologies a strong temporal correlation has long been known to exist between the pathological activation of microglia and dysfunction of neuronal activity. Recent studies have convincingly shown that alteration of microglial function is responsible for pathological neuronal activity. This causal relationship has also been demonstrated in mice bearing loss-of-function mutations in genes specifically expressed by microglia. In addition to these long-term regulations of neuronal activity, recent data show that microglia can also rapidly regulate neuronal activity, thereby acting as partners of neurotransmission.

Keywords: glial cells; inflammation; microglia; neurotransmission; synapse.

Figure 1

Microglia are genuine partners of synaptic transmission. (A) In acute rodent brain slices, stimulation of microglia by LPS induces the rapid release of ATP, which recruits astrocytes. Upon purinergic stimulation, astrocytes release glutamate, inducing a mGluR-dependent release of presynaptic glutamate (Pascual et al., 2012). Stimulation of microglia by fractalkine induces the release of adenosine, which decreases neuronal activity (Meucci et al., ; Ragozzino et al., ; Piccinin et al., 2010). (B) In zebrafish larva, active neurons release the ATP that attracts microglial bulbous processes. These processes decrease neuronal activity by an as yet unknown mechanism (Li et al., 2012).