Astrocytes were classically considered as simple supportive cells for neurons without a significant role in information processing by the nervous system. However, considerable amounts of evidence obtained by several groups during the past years demonstrated the existence of a bidirectional communication between astrocytes and neurons, which prompted a re-examination of the role of astrocytes in the physiology of the nervous system. While neurons base their excitability on electrical signals generated across the membrane, astrocytes base their cellular excitability on variations of the Ca2+ concentration in the cytosol. This article discusses our current knowledge of the properties of the synaptically evoked astrocyte Ca2+ signal, which reveals that astrocytes display integrative properties for synaptic information processing. Astrocytes respond selectively to different axon pathways, discriminate between the activity of different synapses and their Ca2+ signal is non-linearly modulated by the simultaneous activity of different synaptic inputs. Furthermore, this Ca2+ signal modulation depends on astrocyte cellular intrinsic properties and is bidirectionally regulated by the level of synaptic activity. Finally, astrocyte Ca2+ elevations can trigger the release of gliotransmitters, which modulate neuronal activity as well as synaptic transmission and plasticity, hence granting the bidirectional communication with neurons. Consequently, astrocytes can be considered as cellular elements involved in information processing by the nervous system.

Mounting evidence demonstrates that glial cells might have important roles in regulating the physiology and behavior of adult animals. We summarize some of this evidence here, with an emphasis on the roles of glia of the differentiated nervous system in controlling neuronal excitability, behavior and plasticity. In the review we highlight studies in Drosophila and discuss results from the analysis of mammalian astrocytes that demonstrate roles for glia in the adult nervous system.

NG2 cells represent a unique glial cell population that is distributed widely throughout the developing and adult CNS and is distinct from astrocytes, mature oligodendrocytes and microglia. The ability of NG2 cells to differentiate into myelinating oligodendrocytes has been documented in vivo and in vitro. We reported recently that NG2 cells in the forebrain differentiate into myelinating oligodendrocytes but into a subpopulation of protoplasmic astrocytes (Zhu et al., 2008). However, the in vivo fate of NG2 cells in the spinal cord and cerebellum has remained unknown. To investigate the fate of NG2 cells in caudal central nervous system (CNS) regions in vivo, we examined the phenotype of cells that express EGFP in mice that are double transgenic for NG2CreBAC and the Cre reporter Z/EG. The fate of NG2 cells can be studied in these mice by permanent expression of EGFP in cells that have undergone Cre-mediated recombination in NG2 cells. We find that NG2 cells give rise to oligodendrocytes in both gray and white matter of the spinal cord and cerebellum, and to protoplasmic astrocytes in the gray matter of the spinal cord. However, NG2 cells do not give rise to astrocytes in the white matter of the spinal cord and cerebellum. These observations indicate that NG2 cells serve as precursor cells for oligodendrocytes and a subpopulation of protoplasmic astrocytes throughout the rostrocaudal axis of the CNS.

Cell contact-dependent signaling is a major regulatory mechanism in the organization of developing tissues and in the reorganization (post-injury responses) of specialized tissues in multicellular organisms. In this review we contribute to the further understanding of post-injury recovery processes in adult nervous tissue. We emphasize evidence that supports the involvement of cell contact-inhibition signaling in the cell proliferation, growth and differentiation that occurs during healing and neural reorganization after brain damage.

A key neurotrophin responsible for the survival and function of basal forebrain (BF) cholinergic neurons is brain-derived neurotrophic factor (BDNF). A number of studies now indicate that a source of this factor may be BF astrocytes. This study was designed to define the role of BF-astrocyte-derived BDNF on cholinergic neurons. Moreover, it investigated regulatory events that modulate BDNF content and release. In initial work BDNF derived from BF-astrocyte-conditioned medium (ACM) was found to increase both numbers of BF acetylcholinesterase (AChE+) cholinergic neurons and the cholinergic synthetic enzyme choline acetyltransferase (ChAT). Western blots, immunocytochemistry and pharmacological inhibition studies revealed that glutamate, through group I metabotropic glutamate receptors (mGluR), increases the intracellular levels of BDNF in BF astrocytes in culture, as well as its release. Furthermore, the release of BDNF is mediated by the actions of PLC, IP3 and internal stores of Ca2+. These results suggest that BF astrocytes serve as local sources of BDNF for cholinergic neurons, and that they may be regulated as such by the neuronal signal, glutamate, through the mediation of group I metabotropic receptors and the PLC pathway.

Activity-dependent signaling between neurons and astrocytes contributes to experience-dependent plasticity and development of the nervous system. However, mechanisms responsible for neuron–glial interactions and the releasable factors that underlie these processes are not well understood. The pro-inflammatory cytokine, leukemia-inhibitory factor (LIF), is transiently expressed postnatally by glial cells in the hippocampus and rapidly up-regulated by enhanced neural activity following seizures. To test the hypothesis that spontaneous neural activity regulates glial development in hippocampus via LIF signaling, we blocked spontaneous activity with the sodium channel blocker tetrodotoxin (TTX) in mixed hippocampal cell cultures in combination with blockers of LIF and purinergic signaling. TTX decreased the number of GFAP-expressing astrocytes in hippocampal cell culture. Furthermore, blocking purinergic signaling by P2Y receptors contributed to reduced numbers of astrocytes. Blocking activity or purinergic signaling in the presence of function-blocking antibodies to LIF did not further decrease the number of astrocytes. Moreover, hippocampal cell cultures prepared from LIF −/− mice had reduced numbers of astrocytes and activity-dependent neuron–glial signaling promoting differentiation of astrocytes was absent. The results show that endogenous LIF is required for normal development of hippocampal astrocytes, and this process is regulated by spontaneous neural impulse activity through the release of ATP.