Rapid communication between neurons and astrocytes in primary cortical cultures

Abstract

The identification of neurotransmitter receptors and voltage-sensitive ion channels on astrocytes (reviewed by Barres, 1991) has renewed interest in how these cells respond to neuronal activity. To investigate the physiology of neuron astrocyte signaling, we have employed primary cortical cultures that contain both neuronal and glial cells. As the neurons in these cultures exhibit synchronous spontaneous synaptic activity, we have used both calcium imaging and whole-cell recording techniques to identify physiological activity in astrocytes related to neuronal activity. Whole-cell voltage-clamp records from astrocytes revealed rapid inward currents that coincide with bursts of electrical activity in neighboring neurons. Calcium imaging studies demonstrate that these currents in astrocytes are not always associated with slowly propagating calcium waves. Inclusion of the dye Lucifer yellow within patch pipettes confirmed that astrocytes are extensively coupled to each other but not to adjacent neurons, indicating that the currents observed are not due to gap junction connections between these cell types. These currents do not reflect widespread diffusion of glutamate or potassium released during neuronal activity since a population of small, round, multipolar presumed glial cells that are not dye coupled to adjacent cells did not display electrical currents coincident with neuronal firing, even though they respond to locally applied glutamate and potassium. These findings indicate that, in addition to the relatively slow signaling conveyed by calcium waves, astrocytes also display rapid electrical responses to neuronal activity.

Impact of Cytoplasmic Calcium Buffering on the Spatial and Temporal Characteristics of Intercellular Calcium Signals in Astrocytes

“…This signaling activity is not restricted to astrocytes, because it was recently found to modulate (Nedergaard, 1994) and be modulated by neuronal and axonal activity (Dani et al, 1992;Kriegler and Chiu, 1993;Murphy et al, 1993). Consequently, these findings have transformed the classical view of astrocytes from that of passive, structural, and supportive cells to one in which these cells may actively participate in information processing and, hence, in brain f unctioning (Nedergaard, 1994;Parpura et al, 1994).…”

Regulation of glial metabolism studied by 13C‐NMR

“…In particular, the very low external glutamate concentration (1-3 mM) compared with its transmitter pool in the synaptic vesicles (approximately 100 mM) requires efficient mechanisms to maintain such a high ratio of intra-/extracellular glutamate. High-affinity glutamate transporters exist in neurons and astrocytes, but the majority of functional glutamate is taken up by glial glutamate transporters 14,15 and the expression of astrocytic glutamate carriers is most prominent in those brain regions with the most extensive glutamate transmission. 16 After uptake of glutamate into the astrocytes, glutamate is converted to glutamine via the glial-specific enzyme glutamine synthetase (GS).…”

α‐Latrotoxin stimulates glutamate release from cortical astrocytes in cell culture

“…While initially they were thought to be a 'nerve glue' [1], it is clear that they also have the potential to play dynamic roles. Neurons have been shown to signal to adjacent glia [2][3][4]. Waves of calcium can propagate amongst electrically coupled glia [2,[5][6][7][8][9], and glia can signal back to adjacent neurons [10,11].…”