Modulation of Synaptic Activity

As previously mentioned, astrocytes possess many of the characteristics that would allow them to play an active role in the regulation of neuronal activity, particularly in synaptic transmission. Astrocytes tightly surround synapses; they possess ion channels and receptors for various neurotransmitters and are therefore in a good position to regulate the molecular environment of their associated neuronal set. As discussed previously, two mechanisms, not mutually exclusive—gap junction coupling and neurotransmitter release—may mediate the propagation of Ca2+ waves in the astrocyte network. Other neurotransmit-ters, such as norepinephrine and GABA, have also been shown to evoke [Ca2 + ],- increases in astrocytes from hippocampal slices, indicating that neuron/ astrocyte signaling is not restricted to glutamatergic synapses. Moreover, it has been shown that astrocytes are in turn able to release glutamate and activate the neighboring neurons. Glutamate released from astro-cytes can activate either neuronal NMDA receptors or mGluRs and in this way facilitate or depress synaptic activity. Overall, when releasing glutamate, presynap-tic neuronal endings signal not only to postsynaptic neurons but also to perisynaptic astrocytes, which can reply by releasing glutamate and inducing [Ca2+], changes in the same or in different neurons. This activation of astrocytes by synaptically released glutamate is finely tuned, depending on the intensity and frequency of neuronal activity, indicating plasticity of the astrocyte response.

Other transcellular messengers, such as nitric oxide (NO) and arachidonic acid or its metabolites, are involved in the interactions between neurons and astrocytes. For instance, astrocytes as well as neurons respond to glutamate by releasing arachidonic acid, which in turn participates in the Ca2 + -dependent glutamate release by astrocytes. Arachidonic acid and ATP also stimulate glycogenolysis in astrocytes; these molecules are involved in the metabolic cross talk between astrocytes and neurons. Glial cells also produce NO in response to cytokines released in inflammatory conditions, thereby affecting the reup-take of glutamate by astrocyte. In this context, excessive NO production in the brain has been correlated with neurotoxicity and the pathogenesis of

Synaptic signalling

Synaptic signalling

Astrocytic modulation

Figure 4 New role for astrocytes: processing of information in the CNS (adapted from S. Smith, 1994, Curr. Biol. 9, 807-810).

Astrocytic modulation

Figure 4 New role for astrocytes: processing of information in the CNS (adapted from S. Smith, 1994, Curr. Biol. 9, 807-810).

several neurodegenerative diseases, such as Alzheimer's disease.

Prostaglandins (PGs) are synthesized in astrocytes and also induce a Ca2+-dependent glutamate release. In many brain pathologies or injuries, PG levels have been reported to increase, suggesting that the dysre-gulation of PG-dependent glutamate release from astrocytes could participate in neurotoxic cascades. These data again indicate the existence of an integrated glutamatergic cross talk between neurons and astro-cytes that may play critical roles both in synaptic plasticity and in neurotoxicity.

Another aspect recently evaluated is the role of glial cells in synaptogenesis. In glia-free cultures, retinal ganglion cells form synapses with normal ultrastructure but display little spontaneous synaptic activity and high failure rates in evoked synaptic transmission. In contrast, when cocultured with glial cells, retinal ganglion cells show an increase in the number, frequency, and amplitude of spontaneous postsynaptic currents and also fewer transmissions failures.

Therefore, although lacking the excitability associated with neurons, glial cells are more actively involved in brain function than had been previously thought. Indeed, it appears that glia is intimately associated with neurons through an exchange of signals regulated by the same types of receptors as those found in neurons (Fig. 4).

Understanding And Treating Autism

Understanding And Treating Autism

Whenever a doctor informs the parents that their child is suffering with Autism, the first & foremost question that is thrown over him is - How did it happen? How did my child get this disease? Well, there is no definite answer to what are the exact causes of Autism.

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