Diversity and specificity of glial cell responses in the thalamus (Commentary on Parri et al.)

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Accumulating evidence indicates that glial cells directly influence neuronal information processing in the nervous system. Based initially on in vitro studies and focusing on astrocytes (Volterra & Meldolesi, 2005; Haydon & Carmignoto, 2006; Perea et al., 2009), bi-directional interactions between glial cells and neurons have been demonstrated; the existence of these interactions is now also supported by in vivo approaches (Wang et al., 2006; Winship et al., 2007; Petzold et al., 2008; Schummers et al., 2008; Halassa et al., 2009; Nimmerjahn et al., 2009). Yet, ‘gliophysiology’, specifically how neuronal network activities recruit different types of glial cells, remains poorly understood. In this context, the study of Parri et al. (2010) highlighted in this issue of EJN provides an important basis for understanding the physiology of neuron–glia interactions in thalamic processing of sensory information.

The authors used a combination of electrophysiological and calcium-imaging techniques to study glial cell responses in acute slices of rat ventrobasal (VB) nucleus of the thalamus. The VB receives excitatory somatosensory inputs, notably from the vibrissae, and projects to the somatosensory cortex from which an excitatory projection feedbacks onto the VB. The sensory and the cortical inputs to the VB are both glutamatergic. Parri et al. demonstrate that, in astrocytes, stimulation of either of these inputs evokes delayed, slow calcium responses. These calcium responses require stimulation of metabotropic glutamatergic receptors (mGluR5). Furthermore, individual VB astrocytes exhibited different sensitivities to sensory and cortical afferent inputs, and were overall more readily recruited by cortical inputs. As stated in Parri et al., the larger number of cortical, when compared with sensory, afferent fibres innervating the VB may account for these observations. Thus, the results of Parri et al. suggest that VB astrocytes might be important in sensory input processing and physiological brain states that rely on the recurrent activation of the cortico-thalamic pathway. Interestingly, the authors also showed that direct stimulation of astrocytes triggers slow excitatory NMDA receptor-mediated currents in VB neurons, confirming results from previous research and obtained in several brain regions (Parri et al., 2001; Angulo et al., 2004; Fellin et al., 2004; Perea & Araque, 2005; Kozlov et al., 2006; D’Ascenzo et al., 2007). Such slow currents may further prolong and favour excitation in the thalamo-cortical loop.

In a second part of their article, Parri et al. analysed the responses evoked by the same afferent pathways in another type of glial cells, oligodendrocyte precursors expressing the proteoglycan NG2 (NG2 cells; also known as polydendrocytes or synantocytes). These glial cells play a critical role in myelination during postnatal brain maturation, and a pool of these precursors is maintained in the adult brain (Nishiyama et al., 2005). Whereas astrocytes are closely associated with synapses but rarely form true synaptic connections with neurons, glutamatergic and GABAergic synapses are present between neurons and NG2 cells (Bergles et al., 2010). In the VB, responses of NG2 cells to sensory and cortical inputs differed markedly from those of astrocytes: stimulation of the afferent pathways did not trigger slow calcium responses in NG2 cells. Instead, stimulation induced brief synaptic currents mediated by the activation of AMPA receptors. Moreover, the majority of NG2 cells responded to the stimulation of both afferent pathways. Parri et al. also demonstrate that depolarizations inducing a rise of calcium in NG2 cells did not trigger any detectable responses in neighbouring neurons.

The authors conclude that the two types of glial cell are differently and selectively recruited by the major VB excitatory inputs, and that their responses exhibit different properties to those of thalamocortical neurons. The study of Parri et al. is the first comparative analysis of thalamic astrocyte and NG2 cell responses to stimulation of sensory and cortical inputs, and provides us with a challenging hypothesis on the role of astrocytes in the modulation of thalamocortical loops.

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