Wolf F, Kirchhoff F.
Neuroscience. Imaging astrocyte activity.
Science. 2008 Jun 20;320(5883):1597-9.
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The new findings of Schummers, Yu, and Sur are an important and interesting contribution to our understanding of the physiological role of astrocytes in brain function in vivo. Their findings provide strong evidence that rather than acting as a support network for neurons, astrocytes may be part of a neurovascular functional unit, playing an active role in information processing. By performing two-photon imaging of calcium signals in ferret visual cortex, they find that astrocytes display distinct spatial receptive fields and sharp tuning to visual features such as orientation and spatial frequency. (This finding is highly reminiscent of a prior study of Kelly and Van Essen , who showed using microelectrode recording that glial cells in the primary visual cortex responded to visual stimuli with slow graded depolarizations, and that many of them showed a preference for a stimulus orientation similar to the optimal orientation for adjacent neurons.) Interestingly, the tuning of the astrocyte to these responses is even higher than that of the neurons, suggesting that they are important participants and controllers of the functional response. Moreover, when they pharmacologically block the activation of glutamate transporter current in astrocytes (that is normally stimulated by neuronal presynaptic glutamate release), they powerfully block the local vascular dilatation associated with visual sensory stimuli. (Similarly, Gurden et al.  found in the olfactory bulb that presynaptic glutamate release and uptake by astrocytes form a critical pathway through which neural activity is linked to metabolic processing and hence to functional imaging signals, and that astrocyte glutamate transporters played a key role in activating an astrocyte intracellular calcium response.) Significantly, they show that specific visual stimuli induce focal astrocyte activation rather than glial calcium wave activity, and that neighboring astrocytes behave relatively independently of each other. Because activated astrocytes may release neuroactive substances (though probably not glutamate) that act on synapses or alter synaptic responsiveness, it will be important in the future to investigate the role of astrocyte activation on neuronal responses to visual stimuli.
The present findings strongly suggest that astrocytes play a critical role in information processing in the brain and that a cellular circuit of neurons, astrocytes, and blood vessels work together to control brain function. It is interesting that in a mouse model of Alzheimer disease, there is poor vasodilation in response to sensory stimuli (Takano et al., 2007). These investigators suggested that in this mouse model of Alzheimer disease, abnormal astrocytic activity may contribute to vascular instability in AD and thereby to neuronal demise. Given that reactive astrocytes have been found in neurodegenerative diseases (such as ALS) to strongly downregulate their glutamate transporters, the new findings of Schummers et al. help to explain the findings of Takano et al. (2007). Astrocytes lacking glutamate transporters would be predicted to be unable to elevate their intracellular calcium levels and thus unable to induce local vasodilation. If such an anomaly is more generalized throughout an Alzheimer’s affected brain (as would be predicted by the widespread gliosis), this could help to explain the widespread dysfunction of cognitive circuits in this disease.
Kelly JP, Van Essen DC.
Cell structure and function in the visual cortex of the cat.
J Physiol. 1974 May;238(3):515-47.
Gurden H, Uchida N, Mainen ZF.
Sensory-evoked intrinsic optical signals in the olfactory bulb are coupled to glutamate release and uptake.
Neuron. 2006 Oct 19;52(2):335-45.
Takano T, Han X, Deane R, Zlokovic B, Nedergaard M.
Two-photon imaging of astrocytic Ca2+ signaling and the microvasculature in experimental mice models of Alzheimer's disease.
Ann N Y Acad Sci. 2007 Feb;1097:40-50.
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