Starring role in the brain for astrocytes

The 19th century histologists who discovered the neuron also found that the nervous system contains another type of cell. They assumed that the role of these other cells was to provide structural support for neurons, and so named them glia (meaning "glue"). Subsequently, investigators focused their attention on neurons, which they considered to be the key players in brain function, and glia were largely ignored.

The view that glia play a secondary role in brain function persisted for about a hundred years. Recently, however, this has begun to change, and it is now clear that glia play multiple significant roles in brain function. Now, a study published in Science shows that astrocytes regulate the flow of blood in the visual cortex, suggesting that function of these cells is the key determinant of the signal detected by functional magnetic resonance imaging (fMRI). More interesting is the finding that the astrocytes can also do what neurons in the visual cortex do, only better.

Astrocytes get their name from their star-shaped appearance, as depicted in the diagram below, by Santiago Ramon y Cajal. Each cell has a small number of branched processes ending in expanded structures called endfeet. Studies published over the past decade show that astrocytes synthesize and release the excitatory neurotransmitter glutamate; remove glutamate from the synapse by active transport; and form synaptic connections with nerve cells.

Astrocytic endfeet are known to envelop the synapses on dendritic spines in the brain; in response to stimulation, their grasp on the spines becomes firmer, so increases the efficacy of synaptic transmission by bringing the pre- and postsynaptic elements into closer apposition. Astrocytes have already been implicated in the regulation of cerebral blood flow - their activation dilates blood vessels and the endfeet have been observed to be intimately associated with blood vessels.

The new work, led by Mriganka Sur of the Department of Brain and Cognitive Sciences at MIT, confirms that astrocytes are indeed involved in the flow of blood in the brain. Using two-photon microscopy, Sur and his colleagues examined the responses to visual stimuli of astrocytes in the visual cortex of live ferrets. They found that the cells responded to the stimuli with an increase in calcium ion concentration, a response that is usually regarded as characterizing neuronal activity.

Subsets of neurons in the primary visual cortex are responsive to specific types of stimuli. Some are selectively activated by horizontal lines or bars moving across the visual field; others are activated by vertical bars, and yet others by bars at intermediate angles. These so-called "simple" cells detect, among other things, the edges of objects. As their combined activity is integrated at progressively higher levels of processing, an image is constructed in a step-wise manner.

Significantly, Sur's team observed that the astrocytes were also activated by stimuli of specific orientations. Their responses were the same as those of neighbouring neurons, but occurred several seconds later. Furthermore, their orientation selectivity mapped onto the cortex in synchrony with that of the neurons. And surprisingly, the astrocytes were more selective than the neurons, with their receptive fields more sharply tuned: the neurons responded to stimuli up to 20 degrees from the preferred orientation, but the astrocytes responded only to stimuli that differed by 10 degrees or less.

Finally, the researchers found that application of compounds which block astrocyte activity significantly reduced blood flow in the visual cortex. They suggest that astrocytes act on blood vessels after a signal received from neighbouring neurons. This has implications for functional neuroimaging, which measures neuronal activity indirectly by detecting changes in blood flow (active parts of the brain need an additional supply of oxygen). It links neuronal activity to blood flow, and suggests that anything affecting astrocyte function will also affect the fMRI signal.

Another type of cell is also known to regulate blood flow. In 2006, researchers from UCL showed that muscle cells called pericytes control blood flow through capillaries in the rat cerebellum and retina. Pericytes straddle the vessels and extend their finger-like processes them; the processes tighten or loosen their grip on the vessel in response to neurotransmitters.

Sur's group is now investigating the possible role of astrocytes in the changes in blood flow that occur in neurological disorders such as vascular dementia and Alzheimer's Disease. Future work will undoubtedly elucidate the mechanism by which astrocytes control blood flow, and distinguish the role of astrocytes from that of pericytes. But most intriguing of all is the possibility that astrocytes are involved in the processing of visual information.

Related:

• 6 iconoclastic discoveries about the brain
• Astrocytes take centre stage in brain function
• Getting a grip on cerebral blood flow
• Nerve glue comes unstuck

Schummers, J. et al (2008). Tuned Responses of Astrocytes and Their Influence on Hemodynamic Signals in the Visual Cortex. Science 320: 1638-1643. DOI: 10.1126/science.1156120