Brain function is recognized to rely on neuronal activity and signaling processes between neurons, whereas astrocytes are generally considered to play supportive roles for proper neuronal function. However, accumulating evidence indicates that astrocytes sense and control neuronal and synaptic activity, indicating that neuron and astrocytes reciprocally communicate. While this evidence has been obtained in experimental animal models, whether this bidirectional signaling between astrocytes and neurons occurs in human brain remains unknown. We have investigated the existence of astrocyte–neuron communication in human brain tissue, using electrophysiological and Ca²⁺ imaging techniques in slices of the cortex and hippocampus obtained from biopsies from epileptic patients. Cortical and hippocampal human astrocytes displayed spontaneous Ca²⁺ elevations that were independent of neuronal activity. Local application of transmitter receptor agonists or nerve electrical stimulation transiently elevated Ca²⁺ in astrocytes, indicating that human astrocytes detect synaptic activity and respond to synaptically released neurotransmitters, suggesting the existence of neuron-to-astrocyte communication in human brain tissue. Electrophysiological recordings in neurons revealed the presence of slow inward currents (SICs) mediated by NMDA receptor activation. The frequency of SICs increased after local application of ATP that elevated astrocyte Ca²⁺. Therefore, human astrocytes are able to release the gliotransmitter glutamate, which affect neuronal excitability through activation of NMDA receptors in neurons. These results reveal the existence of reciprocal signaling between neurons and astrocytes in human brain tissue, indicating that astrocytes are relevant in human neurophysiology and are involved in human brain function.

Cells in the central nervous system are normally prevented from coming into contact with albumin and other protein components of blood by the existence of a tight blood-brain barrier. Astrocytes and other glial cells proliferate to form glial scars when the blood-brain barrier is breached. In this report we show that albumin is an important blood component responsible for inducing astrocyte proliferation. Albumin also generates maintained trains of calcium spikes in astrocytes. Neither activity depends on blood coagulation, as albumins from both serum and plasma are approximately equally effective. Methanol extraction of albumin abolishes both actions, and recombination of the methanol-extracted factor with extracted albumin restores full activity indistinguishable from that of native albumin. The factor is sensitive to lipase, and the solvent extraction profile is that of a polar lipid.

Focal cortical dysplasia (FCD) is a pathology that is characterized by the abnormal development of the neocortex. Indeed, a wide range of abnormalities in the cortical mantle have been associated with this pathology, including cytoarchitectonic alterations and the presence of dysmorphic neurons, balloon cells and ectopic neurons in the white matter. FCD is commonly associated with epilepsy, and hence we have studied the ultrastructure of cortical tissue resected from three subjects with intractable epilepsy secondary to cortical dysplasia to identify possible alterations in synaptic circuitry, using correlative light and electron microscopic methods. While the balloon cells found in this tissue do not appear to receive synaptic contacts, the ectopic neurons in the white matter were abnormally large and were surrounded by hypertrophic basket formations immunoreactive for the calcium-binding protein parvalbumin. Furthermore, these basket formations formed symmetrical (inhibitory) synapses with both the somata and the proximal portion of the dendrites of these giant ectopic neurons. A quantitative analysis revealed that in the dysplastic tissue, the density of excitatory and inhibitory synapses was different from that of the normal adjacent cortex. Both increases and decreases in synaptic density were observed, as well as changes in the proportion of excitatory and inhibitory synapses. However, we could not establish a common pattern of changes, either in the same patients or between different patients. These results suggest that cortical dysplasia leads to multiple changes in excitatory and inhibitory synaptic circuits. We discuss the possible relationship between these alterations and epilepsy, bearing in mind the possible limitations that preclude the extrapolation of the results to the whole population of epileptic patients with dysplastic neocortex.