Biomedical subjects

Gertrudis Perea

Publications and source records attributed to Gertrudis Perea.

7 recordsLinked to original sources

PubMed2007

Adenosine released by astrocytes contributes to hypoxia-induced modulation of synaptic transmission.

Astrocytes play a critical role in brain homeostasis controlling the local environment in normal as well as in pathological conditions, such as during hypoxic/ischemic insult. Since astrocytes have recently been identified as a source for a wide variety of gliotransmitters that modulate synaptic activity, we investigated whether the hypoxia-induced excitatory synaptic depression might be mediated by adenosine release from astrocytes. We used electrophysiological and Ca2+ imaging techniques in hippocampal slices and transgenic mice, in which ATP released from astrocytes is specifically impaired, as well as chemiluminescent and fluorescence photometric Ca2+ techniques in purified cultured astrocytes. In hippocampal slices, hypoxia induced a transient depression of excitatory synaptic transmission mediated by activation of presynaptic A1 adenosine receptors. The glia-specific metabolic inhibitor fluorocitrate (FC) was as effective as the A1 adenosine receptor antagonist CPT in preventing the hypoxia-induced excitatory synaptic transmission reduction. Furthermore, FC abolished the extracellular adenosine concentration increase during hypoxia in astrocyte cultures. Several lines of evidence suggest that the increase of extracellular adenosine levels during hypoxia does not result from extracellular ATP or cAMP catabolism, and that astrocytes directly release adenosine in response to hypoxia. Adenosine release is negatively modulated by external or internal Ca2+ concentrations. Moreover, adenosine transport inhibitors did not modify the hypoxia-induced effects, suggesting that adenosine was not released by facilitated transport. We conclude that during hypoxia, astrocytes contribute to regulate the excitatory synaptic transmission through the release of adenosine, which acting on A1 adenosine receptors reduces presynaptic transmitter release. Therefore, adenosine release from astrocytes serves as a protective mechanism by down regulating the synaptic activity level during demanding conditions such as transient hypoxia.

Adenosine↗

PubMed2006

Synaptic information processing by astrocytes.

Glial cells were classically considered as supportive cells that do not contribute to information processing in the nervous system. However, considerable amount of evidence obtained by several groups during the last few years has demonstrated the existence of a bidirectional communication between astrocytes and neurons, which prompted a re-examination of the role of glial cells in the physiology of the nervous system. This review will discuss recent advances in the neuron-to-astrocyte communication, focusing on the recently reported properties of the synaptically evoked astrocyte Ca2+ signal that indicate that astrocytes show integrative properties for synaptic information processing. Indeed, we have recently shown that hippocampal astrocytes discriminate between the activity of different synapses, and respond selectively to different axon pathways. Furthermore, the astrocyte Ca2+ signal is modulated by the simultaneous activity of different synaptic inputs. This Ca2+ signal modulation depends on cellular intrinsic properties of the astrocytes, is bidirectionally regulated by the level of synaptic activity, and controls the spatial extension of the intracellular Ca2+ signal. Consequently, we propose that astrocytes can be considered as cellular elements involved in information processing by the nervous system.

Animals↗

PubMed2005

Properties of synaptically evoked astrocyte calcium signal reveal synaptic information processing by astrocytes.

The synaptic control of the astrocytic intracellular Ca2+ is crucial in the reciprocal astrocyte-neuron communication. Using electrophysiological and Ca2+ imaging techniques in rat hippocampal slices, we investigated the astrocytic Ca2+ signal modulation induced by synaptic terminals that use glutamate and acetylcholine. Ca2+ elevations were evoked by glutamate released from Schaffer collaterals and by acetylcholine, but not glutamate, released by alveus stimulation, indicating that astrocytes discriminate the activity of different synapses belonging to different axon pathways. The Ca2+ signal was modulated bidirectionally by simultaneous activation of both pathways, being depressed at high stimulation frequencies and enhanced at low frequencies. The Ca2+ modulation was attributable to astrocytic intrinsic properties, occurred at discrete regions of the processes, and controlled the intracellular expansion of the Ca2+ signal. In turn, astrocyte Ca2+ signal elicited NMDA receptor-mediated currents in pyramidal neurons. Therefore, because astrocytes discriminate and integrate synaptic information, we propose that they can be considered as cellular elements involved in the information processing by the nervous system.

4-Aminopyridine↗

PubMed2004

Glial modulation of synaptic transmission in culture.

Accumulating evidence has demonstrated the existence of bidirectional communication between glial cells and neurons, indicating an important active role of glia in the physiology of the nervous system. Neurotransmitters released by presynaptic terminals during synaptic activity increase intracellular Ca(2+) concentration in adjacent glial cells. In turn, activated glia may release different transmitters that can feed back to neuronal synaptic elements, regulating the postsynaptic neuronal excitability and modulating neurotransmitter release from presynaptic terminals. As a consequence of this evidence, a new concept of the synaptic physiology, the tripartite synapse, has been proposed, in which glial cells play an active role as dynamic regulatory elements in neurotransmission. In the present article we review evidence showing the ability of astrocytes to modulate synaptic transmission directly, with the focus on studies performed on cell culture preparations, which have been proved extremely useful in the characterization of molecular and cellular processes involved in astrocyte-mediated neuromodulation.

Animals↗

PubMed2002

Synaptically released acetylcholine evokes Ca2+ elevations in astrocytes in hippocampal slices.

Recent results have demonstrated the existence of bidirectional communication between glial cells and neurons. We investigated in brain slices whether rat hippocampal astrocytes respond to acetylcholine synaptically released by an extrinsic pathway. We stimulated the stratum oriens/alveus, which contains cholinergic afferents from the septum and diagonal band of Broca, and recorded whole-cell membrane currents and intracellular Ca2+ levels of astrocytes located in the hippocampal stratum oriens. Nerve-fiber stimulation evoked a long-lasting inward current and increased the Ca2+ levels in astrocytes. Both astrocytic responses were abolished by tetrodotoxin or Cd2+ and were increased by 4-aminopyridine, indicating that the responses were attributable to synaptically released neurotransmitter. The inward current was inhibited by glutamate transporter antagonists, indicating that it was attributable to the electrogenic glutamate transporter activity. The synaptically evoked intracellular Ca2+ elevations were not affected by glutamate receptor antagonists but were abolished by atropine, indicating that they were mediated by muscarinic cholinergic receptors. Thapsigargin prevented the Ca2+ elevation but did not modify the inward current, indicating that the Ca2+ signal was attributable to intracellular Ca2+ mobilization. These results indicate that hippocampal astrocytes respond to acetylcholine released by synaptic terminals. The synaptically released acetylcholine acts on muscarinic receptors, mobilizing Ca2+ from the intracellular stores. Different regions in the recorded astrocytes showed independent stimulus-induced Ca2+ variations, suggesting the existence of subcellular domains in the astrocytic responses evoked by the synaptic cholinergic activity. Therefore, our results show the existence of cholinergic neuron-astrocyte signaling and suggest that astrocytes are a target of axonal inputs from different brain areas.

Acetylcholine↗

PubMedDate not supplied

Glial calcium signaling and neuron-glia communication.

The existence of bidirectional signaling between astrocytes and neurons has revealed an important active role of astrocytes in the physiology of the nervous system. As a consequence, there is a new concept of the synaptic physiology-"the tripartite synapse", where astrocytes exchange information with the pre- and postsynaptic elements and participate as dynamic regulatory elements in neurotransmission. The control of the Ca2+ excitability in astrocytes is a key element in this loop of information exchange. The ability of astrocytes to respond to neuronal activity and discriminate between the activity of different synapses, the modulation of the astrocytic cellular excitability by the synaptic activity, and the expression of cellular intrinsic properties indicate that astrocytes are endowed with cellular computational characteristics that process synaptic information. Therefore, we propose that astrocytes can be considered as cellular elements involved in the information processing by the nervous system.

Animals↗

PubMedDate not supplied

Communication between astrocytes and neurons: a complex language.

In recent years, accumulating evidence suggests the existence of bidirectional communication between astrocytes and neurons, indicating an important active role of astrocytes in the physiology of the nervous system. As a consequence of this evidence, a new concept of the synaptic physiology--"the tripartite synapse"--has been proposed, in which the synapse is formed by three functional elements, i.e. the pre- and postsynaptic elements and the surrounding astrocytes. In the present article we review and discuss the current knowledge on the cellular mechanisms and physiological properties of this communication that displays highly complex characteristics. We are beginning to realize that the communication between astrocytes and neurons uses a quite complex language.

Animals↗