Gap junctions synchronize the firing of inhibitory interneurons in guinea pig hippocampus

Yang, Qizong; Michelson, Hillary B.

doi:10.1016/s0006-8993(01)02582-3

Cited by 55 publications

(25 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The electrical communication between neurons through gap junctions (GJs) is one of the most important neural mechanisms underlying the synchronization of cell firing (Bukauskas & Weingart, ; Chen & de Haan, ; Carlen et al ., ; Traub et al ., ; Yang & Michelson, ; Jahromi et al ., ; Traub et al ., ). The GJs coupling permits the rapid passage of ion current between neurons and has been identified in different structures of the CNS (MacVicar & Dudek, ; Carlen et al ., ).…”

Section: In Vitro Recorded Theta Rhythmmentioning

confidence: 99%

The generation of theta rhythm in hippocampal formation maintainedin vitro

Kowalczyk

Bocian

Konopacki

2012

Eur J of Neuroscience

View full text Add to dashboard Cite

The most spectacular example of oscillations and synchrony which appear in the brain is the rhythmic slow activity (theta) of the limbic cortex. Theta rhythm is the best synchronized electroencephalographic activity that can be recorded from the mammalian brain. Hippocampal formation is considered to be the main structure involved in the generation of this activity. Although detailed studies of the physiology and pharmacology of theta-band oscillations have been carried out since the early 1950s, the first demonstration of atropine-sensitive theta rhythm, recorded in completely deafferented hippocampal slices of a rat, was performed in the second half of the 1980s. Since the discovery of cholinergically induced in vitro theta rhythm recorded from hippocampal formation slices, the central mechanisms underlying theta generation have been successfully studied in in vitro conditions. Most of these experiments were focused on the basic question regarding the similarities between the cholinergically induced theta activity and theta rhythm examined in vivo. The results of numerous in vitro experiments strongly suggest that cholinergically induced theta rhythm recorded in hippocampal slices is a useful analogue of theta observed in intact animals, and could be helpful in searching for the mechanisms of oscillations and synchrony in the central nervous system neuronal networks. The objective of the present review is to discuss the main results of experiments concerning theta oscillations recorded in in vitro conditions. It is our intent to provide, on the basis of these results, the characteristics of essential mechanisms underlying the generation of atropine-sensitive in vitro theta.

show abstract

Section: In Vitro Recorded Theta Rhythmmentioning

confidence: 99%

The generation of theta rhythm in hippocampal formation maintainedin vitro

Kowalczyk

Bocian

Konopacki

2012

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

“…Although previous reports have not described significant effects of CBX on intrinsic neuronal properties [11,21,25,34,40], other evidence in cell culture suggests an action on neuronal excitability, independent of the GJ [32], and such effect cannot be totally excluded in slices. However, the amplitude of fiber responses was not altered after CBX application in rat cortical slices, suggesting that this compound does not produce a large unspecific modification of excitability.…”

Section: Action and Specificity Of Cbx In Thalamocortical Slicesmentioning

confidence: 79%

Decrease of neocortical paired-pulse depression in GAERS and possible implication of gap junctions

Gigout¹,

Louvel²,

Pumain³

2015

Neuroscience Letters

View full text Add to dashboard Cite

“…Taken together, the observations presented so far suggest that the reported effects of carbenoxolone on GABAergic discharges induced by 4‐AP (Ross et al . 2000; Yang & Michelson, 2001; Traub et al . 2001; Lamsa & Kaila, 1997; Gigout et al .…”

Section: Resultsmentioning

confidence: 99%

“…This activity depends on depolarizing GABAergic transmission (Lamsa & Taira, 2003;Kantrowitz et al 2005;Zsiros et al 2007) and can be conveniently isolated in vitro following blockade of ionotropic glutamate receptors (Perrault & Avoli, 1992). Application of gap junction blockers such as carbenoxolone, has been consistently reported to reduce 4-AP-dependent synchronization both in vivo (Szente et al 2002;Gajda et al 2003Gajda et al , 2005Gajda et al , 2006Medina-Ceja et al 2008) and in vitro (Ross et al 2000;Yang & Michelson, 2001;Traub et al 2001;Lamsa & Taira, 2003;Gigout et al 2006;Zsiros et al 2007). Unfortunately, currently available blockers (reviewed by Juszczak & Swiergiel, 2009) bind to several targets other than gap junctions, making a straightforward interpretation of pharmacological experiments problematic (Tovar et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Is connexin36 critical for GABAergic hypersynchronization in the hippocampus?

Beaumont

Maccaferri

2011

The Journal of Physiology

View full text Add to dashboard Cite

Non-technical summary In some forms of incurable epilepsies, GABAergic interneurons, which physiologically mediate inhibition in the brain, are thought to mediate excitation. The presence of a specific form of electrical communication between these cells, which is mediated by structures called gap junctions, has been proposed to be involved in the generation of synchronized epileptiform discharges. In support of this hypothesis is the repeated finding in the literature that the drug carbenoxolone, which is an effective blocker of gap junction function, decreases epileptiform activity in models of epilepsy both in vivo and in vitro. Our work challenges this view and highlights additional side-effects of carbenoxolone, which are unrelated to gap junctions, but seem to contribute to its reported antiepileptic activity. A full knowledge of these additional mechanisms is important for the rational development of new molecules to be used in the therapy of epilepsy.Abstract Synchronous bursting of cortical GABAergic interneurons is important in epilepsies associated with excitatory GABAergic signalling. If electrical coupling was critical for the generation of this pathological activity, then the development of selective blockers of connexin36-based interneuronal gap junctions could be of therapeutic value. We have addressed this issue in the 4-aminopyridine model of epilepsy in vitro by comparing GABAergic epileptiform currents and their sensitivity to gap junction blockers in wild-type vs. connexin36 knockout mice. Although electrical coupling was abolished in stratum lacunosum-moleculare interneurons from knockout animals, epileptiform currents were not eliminated. Furthermore, epileptiform currents propagated similarly across hippocampal layers in the two genotypic groups. Blockade of electrical coupling with carbenoxolone suppressed amplitude, frequency and half-width of the epileptiform currents both in wild-type and in knockout animals, whereas mefloquine had no effects. Carbenoxolone also depressed responses to exogenous and synaptic GABA application onto interneurons. We conclude that, in the 4-aminopyridine model of epilepsy in vitro, connexin36 is not critical for the generation of epileptiform discharges in GABAergic networks and that the observed antiepileptic effects of carbenoxolone are likely to be due to blockade of GABA A receptors and not of connexin36-based gap junctions. Lastly, because of its chemical structure and its effects on amplitude and kinetics of GABAergic currents, we tested the hypothesis that carbenoxolone acted via specific sites on GABA A receptors, such as the one mediating the effects of the neurosteroid pregnenolone sulfate, or the allosteric regulatory site of benzodiazepines/β-carbolines. Our results suggest that neither of these is involved.

show abstract

Gap junctions synchronize the firing of inhibitory interneurons in guinea pig hippocampus

Cited by 55 publications

References 15 publications

The generation of theta rhythm in hippocampal formation maintainedin vitro

The generation of theta rhythm in hippocampal formation maintainedin vitro

Decrease of neocortical paired-pulse depression in GAERS and possible implication of gap junctions

Is connexin36 critical for GABAergic hypersynchronization in the hippocampus?

Contact Info

Product

Resources

About