Neuronal–glial interactions and behaviour

Laming, Peter R.; Kimelberg, Harold K.; Robinson, Stephen R.; Salm, A.K.; Hawrylak, Nicholas; Müller, Christian M.; Roots, Betty I.; Ng, Kim T.

doi:10.1016/s0149-7634(99)00080-9

Cited by 194 publications

(125 citation statements)

References 430 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…These changes, therefore, may be an essential mechanism for physiological functions such as milk ejection and body fluid homeostasis. Astrocytic regulation of diffusion in the ECS could be relevant in other brain regions in which similar physiological neuroglial remodeling has been documented (11,13,29,30). It is highly likely, then, that astrocytes not only influence communication between independent adjacent synapses but, more generally, also constitute a potent regulator of extrasynaptic or volume transmission (12,31) for a variety of active substances including neurotransmitters, peptides, endocannabinoids, or neurosteroids.…”

Section: Discussionmentioning

confidence: 91%

Physiological contribution of the astrocytic environment of neurons to intersynaptic crosstalk

Piet

Vargová

Syková

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

237

173

View full text Add to dashboard Cite

Interactions between separate synaptic inputs converging on the same target appear to contribute to the fine-tuning of information processing in the central nervous system. Intersynaptic crosstalk is made possible by transmitter spillover from the synaptic cleft and its diffusion over a distance to neighboring synapses. This is the case for glutamate, which inhibits ␥-aminobutyric acid (GABA)ergic transmission in several brain regions through the activation of presynaptic receptors. Such heterosynaptic modulation depends on factors that influence diffusion in the extracellular space (ECS). Because glial cells represent a physical barrier to diffusion and, in addition, are essential for glutamate uptake, we investigated the physiological contribution of the astrocytic environment of neurons to glutamate-mediated intersynaptic communication in the brain. Here we show that the reduced astrocytic coverage of magnocellular neurons occurring in the supraoptic nucleus of lactating rats facilitates diffusion in the ECS, as revealed by tortuosity and volume fraction measurements. Under these conditions, glutamate spillover, monitored through metabotropic glutamate receptor-mediated depression of GABAergic transmission, is greatly enhanced. Conversely, impeding diffusion with dextran largely prevents crosstalk between glutamatergic and GABAergic afferent inputs. Astrocytes, therefore, by hindering diffusion in the ECS, regulate intersynaptic communication between neighboring synapses and, probably, overall volume transmission in the brain.

show abstract

Section: Discussionmentioning

confidence: 91%

Physiological contribution of the astrocytic environment of neurons to intersynaptic crosstalk

Piet

Vargová

Syková

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

237

173

View full text Add to dashboard Cite

show abstract

“…In addition, multiple lines of evidence have pointed to a generation of large-scale, slow electric signals by nonneuronal sources, such as the glial cells (17,(36)(37)(38) and the blood-brain barrier (see refs. 14 and 39 and references therein).…”

Section: Discussionmentioning

confidence: 99%

Infraslow oscillations modulate excitability and interictal epileptic activity in the human cortex during sleep

Vanhatalo

Palva

Holmes

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

453

397

View full text Add to dashboard Cite

Human cortical activity has been intensively examined at frequencies ranging from 0.5 Hz to several hundred Hz. Recent studies have, however, reported also infraslow fluctuations in neuronal population activity, magnitude of electroencephalographic oscillations, discrete sleep events, as well as in the occurrence of interictal events. Here we use direct current electroencephalography to demonstrate large-scale infraslow oscillations in the human cortex at frequencies ranging from 0.02 to 0.2 Hz. These oscillations, which are not detectable in conventional electroencephalography because of its limited recording bandwidth (typical lower limit 0.5 Hz), were observed in widespread cortical regions. Notably, the infraslow oscillations were strongly synchronized with faster activities, as well as with the interictal epileptic events and K complexes. Our findings suggest that the infraslow oscillations represent a slow, cyclic modulation of cortical gross excitability, providing also a putative mechanism for the as yet enigmatic aggravation of epileptic activity during sleep.epilepsy ͉ slow cortical oscillations ͉ phase synchrony ͉ direct current electroencephalography ͉ full-band electroencephalography A large body of literature has characterized functional and clinical correlates of cortical oscillatory activity seen in the human electroencephalography (EEG) at frequencies ranging from 0.5 Hz to several hundred Hz (1). In addition to these relatively fast EEG oscillations, some studies have demonstrated infraslow fluctuations in, for instance, neuronal population activity (2-5), EEG power (5-9), discrete sleep events (arousals, spindles, K complexes) (9-12), as well as in the occurrence of epileptic events (4, 11, 13). These observations have raised the possibility that the human cortex may generate infraslow oscillations (ISOs) underlying such fluctuations. ISOs are not detectable in conventional EEG because of its limited recording bandwidth (typical lower limit, 0.5 Hz; ref. 1).In the present study, we used direct current (DC)-coupled EEG scalp recordings (14-16) to demonstrate that ISOs are, in fact, a salient, large-scale feature of the human EEG. They were tightly associated with a cyclic modulation of fast EEG activity as well as discrete EEG events such as K complexes and interictal activity. In analogy with recent studies demonstrating that slow delta oscillations (0.5-1 Hz) may modulate brain excitability (17, 18), our data points to a role of ISOs in the control of gross cortical excitability. Our findings also provide a window on the modulation of interictal epileptiform events (IIEs) and on sleep-epilepsy interactions in the human brain. MethodsSubjects and EEG Recording. We studied 16 subjects (four females; average age, 34.3 years; range, 16-51 years) during overnight (n ϭ 9) or daytime (n ϭ 7) sleep. This study was approved by the Human Subjects Committee of the University of Washington. Twelve subjects were recorded using a custom-made 16-channel DC-coupled EEG amplifier and Ag͞AgCl electrodes (refs....

show abstract

“…Second, breakpoint is used to quantify motivation and reinforcing efficacy (Richardson and Roberts, 1996). Third, behaviorally relevant stimuli can impact astrocyte morphology that can, in turn, influence synaptic efficacy and neuronal responses to salient stimuli (Laming et al, 2000). Though the potential impact of EtOH-seeking behavior during testing cannot be dissociated from astrocyte density, a significant correlation was observed in both the operant and EtOH-IA cohorts that differed markedly in operant responding.…”

Section: Behavioral Relevance Of Astrocyte Densitymentioning

confidence: 99%

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

Bull

Freitas

Zou

et al. 2014

Neuropsychopharmacol

125

106

View full text Add to dashboard Cite

Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH selfadministration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with astrocyte-specific DREADDs. Taken together, our findings demonstrate that NAcore astrocytes can shape the motivation to self-administer ethanol; suggesting that the development of ligands which selectively stimulate astrocytes may be a successful strategy to abate ethanol-seeking behavior.

show abstract

Neuronal–glial interactions and behaviour

Cited by 194 publications

References 430 publications

Physiological contribution of the astrocytic environment of neurons to intersynaptic crosstalk

Physiological contribution of the astrocytic environment of neurons to intersynaptic crosstalk

Infraslow oscillations modulate excitability and interictal epileptic activity in the human cortex during sleep

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

Contact Info

Product

Resources

About