Expression of Connexin36 in the adult and developing rat brain

Belluardo, Natale; Mudò, Giuseppa; Salinaro, Angela Trovato; Gurun, Sabine Le; Charollais, Anne; Serre‐Beinier, Véronique; Amato, Giuseppe; Haefliger, Jacques‐Antoine; Meda, Paolo; Condorelli, D. F.

doi:10.1016/s0006-8993(00)02300-3

Cited by 260 publications

(258 citation statements)

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“…Consistent with this idea, morphological and physiological evidence of this coupling has been obtained (Benardo and Foster 1986;Llinás andYarom 1981, 1986;Sotelo et al 1974). In fact, the density of neuronal gap junctions in the IO is one of the highest in the CNS (Belluardo et al 2000;Condorelli et al 1998;De Zeeuw et al 1995). Moreover, synchronous CS activity remains following block of excitatory and/or inhibitory input to the IO (Lang 2001(Lang , 2002, which, given the virtual lack of local chemical synaptic interactions between IO neurons, further implicates gap junction coupling as the origin of CS synchrony.…”

Section: Significance Of Uniform Olivocerebellar Conduction Time For mentioning

confidence: 52%

“…Indeed, the density of neuronal gap junctions appears to be higher in the IO than in any other CNS region (Belluardo et al 2000;Condorelli et al 1998;De Zeeuw et al 1995). This coupling allows IO neurons to generate precisely (on a millisecond time scale) synchronized activity that results in simultaneous complex spike (CS) activity in the cerebellum (Lang et al 1999;Sasaki et al 1989;Sugihara et al 1993;Yamamoto et al 2001).…”

Section: Introductionmentioning

confidence: 99%

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Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time

Lang¹,

Rosenbluth

2003

Journal of Neurophysiology

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Lang, Eric J. and Jack Rosenbluth. Role of myelination in the development of a uniform olivocerebellar conduction time. J Neurophysiol 89: 2259 -2270, 2003. First published December 18, 2002 10.1152/jn.00922.2002. Purkinje cells generate simultaneous complex spikes as a result of olivocerebellar activity. This synchronization (to within 1 ms) is thought to result from electrotonic coupling of inferior olivary neurons. However, the distance from the inferior olive (IO) varies across the cerebellar cortex. Thus signals generated simultaneously at the IO should arrive asynchronously across the cerebellar cortex, unless the length differences are compensated for. Previously, it was shown that the conduction time from the IO to the cerebellar cortex remains nearly constant at Ϸ4 ms in the rat, implying the existence of such compensatory mechanisms. Here, we examined the role of myelination in generating a constant olivocerebellar conduction time by investigating the latency of complex spikes evoked by IO stimulation during development in normal rats and myelin-deficient mutants. In normal rats, myelination not only reduced overall olivocerebellar conduction time, but also disproportionately reduced the conduction time to vermal lobules, which had the longest response latencies prior to myelination. The net result was a nearly uniform conduction time. In contrast, in myelin-deficient rats, conduction time differences to different parts of the cerebellum remained during the same developmental period. Thus myelination is the primary factor in generating a uniform olivocerebellar conduction time. To test the importance of a uniform conduction time for generating synchronous complex spike activity, multiple electrode recordings were obtained from normal and myelin-deficient rats. Average synchrony levels were higher in normal rats than mutants. Thus the uniform conduction time achieved through myelination of olivocerebellar fibers appears to be essential for the normal expression of complex spike synchrony. I N T R O D U C T I O NInferior olivary (IO) neurons are electrotonically coupled via numerous gap junctions (Llinás and Yarom 1981;Llinás et al. 1974;Sotelo et al. 1974). Indeed, the density of neuronal gap junctions appears to be higher in the IO than in any other CNS region (Belluardo et al. 2000;Condorelli et al. 1998;De Zeeuw et al. 1995). This coupling allows IO neurons to generate precisely (on a millisecond time scale) synchronized activity that results in simultaneous complex spike (CS) activity in the cerebellum (Lang et al. 1999;Sasaki et al. 1989;Sugihara et al. 1993;Yamamoto et al. 2001).Maintenance of the synchronization present in IO discharges presents a challenge for the olivocerebellar system because the length of the olivocerebellar pathway to different points on the cerebellar cortex varies. In rats, there can be more than a twofold difference in the length of the olivocerebellar projection to different regions of the cortex (Sugihara et al. 1993). To preserve the precise synchronization present at...

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Section: Significance Of Uniform Olivocerebellar Conduction Time For mentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time

Lang¹,

Rosenbluth

2003

Journal of Neurophysiology

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“…Thus, these gap junctions must be comprised of other connexins. That is not surprising, as connexin 36 is predominantly or exclusively found in neurons (Condorelli et al, 1998Belluardo et al, 2000;Rash et al, 2001), and connexin 43 is known to be present in the olfactory nerve layer (Paternostro et al, 1995).…”

Section: Discussionmentioning

confidence: 94%

“…Olfactory receptor neurons express mRNA for connexins 43 (Zhang et al, 2000), 45 (Zhang and Restrepo, 2002), and 36 (Zhang and Restrepo, 2003). Furthermore, in immunohistochemical studies for connexin proteins, the olfactory nerve layer of the main olfactory bulb stains intensely for connexin 43 (Paternostro et al, 1995), and possibly also connexin 36 (Zhang and Restrepo, 2003; but see Belluardo et al, 2000). Although these findings suggest that connexin proteins are expressed in the olfactory nerve layer, axonal gap junctions have not been reported to occur in this layer in previous transmission electron microscopy (TEM) studies (Andres, 1969;Berger, 1969;Doucette, 1984;Marin-Padilla and Amieva, 1989;Au et al, 2002).…”

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confidence: 99%

Intercellular interactions in the mammalian olfactory nerve

Blinder

Pumplin

Paul

et al. 2003

J of Comparative Neurology

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The small, unmyelinated axons of olfactory sensory neurons project to the olfactory bulb in densely packed fascicles, an arrangement conducive to axo-axonal interactions. We recently demonstrated ephaptic interactions between these axons in the olfactory nerve layer, the layer of the olfactory bulb in which the axon fascicles interweave and rearrange extensively. In the present study, we hypothesized that the axons, which express connexins, may have another mode of communication: gap junctions. Previous transmission electron microscopy (TEM) studies have failed to demonstrate such junctions. However, the definitive method for detecting gap junctions, freeze fracture, has not been used to examine the interaxonal connections of the olfactory nerve layer. Here, we apply a combined approach of TEM and freeze fracture to determine if gap junctions are present between the olfactory axons. Gap junctions involving olfactory axons were not found. However, by freeze fracture, P faces of both the axons and ensheathing cells (glia that surround the axon fascicles) contained distinctive linear arrays of particles, aligned along the small columns of extracellular space. In axons, few intramembranous particles were present outside of these arrays. Multi-helix proteins, including ion channels and connexin hemichannels, have been shown to be visible as particles by freeze fracture. This suggests that the proteins important for signal transmission are confined to the linear arrays. Such an arrangement would facilitate ephaptic transmission, calcium waves, current oscillations, and paracrine communication and may be important for olfactory neural code processing.Keywords freeze fracture; ultrastructure; olfactory bulb; ephaptic; connexins; hemichannels Olfactory receptor neurons project from the olfactory epithelium to the olfactory bulb by dense bundles of thin, unmyelinated olfactory axons (Marin-Padilla and Amieva, 1989;Daston et al., 1990;Mori, 1993). The high packing density of these axons and the absence of intervening glia suggest that olfactory coding may be affected by axoaxonal interactions.We recently demonstrated (Bokil et al., 2001) that neighboring axons are able to influence each other by ephaptic interactions-current spread through the small extracellular space. We have argued (Bokil et al., 2001) that ephaptic interactions, as well as interneuronal interactions mediated by extruded potassium ions (Bliss and Rosenberg, 1979) First, olfactory receptors of mature mammals are constantly regenerated (Graziadei and Graziadei, 1979;Graziadei and Monti Graziadei, 1983), and developing neurons of the central nervous system are often extensively coupled by gap junctions (reviewed in Kandler and Katz, 1995;Naus and Bani-Yaghoub, 1998;Chang and Balice-Gordon, 2000). Second, olfactory receptor neurons express connexins, the proteins that form gap junctions. Olfactory receptor neurons express mRNA for connexins 43 (Zhang et al., 2000), 45 (Zhang andRestrepo, 2002), and 36 (Zhang andRestrepo, 2003). Furthermore, in immun...

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“…Thus, it is likely that motor patterning may involve activity within neuronal networks coordinated via gap junctions. In the striatum, cells express connexins, the protein building blocks of gap junctions (Belluardo et al 2000;Bennett et al 1999). Striatal neurons also exhibit dye coupling, the transfer of dye molecules between neurons through electrotonic junctions (Cepeda et al 1989).…”

Section: Stimulation Of Dopamine (Da) Receptors In the Striatum Evokementioning

confidence: 99%

A Role for Electrotonic Coupling in the Striatum in the Expression of Dopamine Receptor-mediated Stereotypies,

Moore

Grace

2002

Neuropsychopharmacology

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Stimulation of dopamine (DA) receptors in the striatum evokes a number of alterations in motor behavior in rats, as well as causing several alterations in cellular physiology, including changes in membrane potential, cell excitability, afferent drive, and electrotonic coupling. One cellular property that is potently modulated by DA stimulation is electrotonic coupling, a process shown to subserve motor pattern generation. To examine whether electrotonic coupling plays a role in mediating a specific set of DA receptor-mediated motor behaviors, we tested the effects of two inhibitors of gap junction conductance, carbenoxolone (CARB) and anandamide (AEA), on apomorphine (APO)-induced motor responses. We then used intra-striatal infusions of CARB to determine the role of electrotonic coupling specifically in the ventral striatum in the expression of i.p.) significantly increased motor activity (a composite score) and the frequencies of oral and sniffing stereotypies. APO also disrupted grooming initiation and completion. APO-induced oral stereotypies were selectively blocked by systemic administration of CARB (7.0, 35.0 mg/kg Adaptive behaviors, both learned and spontaneous, consist of sequences of "micro" movements executed by closely-related muscle groups. There is evidence that the initiation and execution of individual movements, such as oral movements involved in feeding, as well as the linking of these movements into a behavioral sequence, depend upon neuronal networks within the Beninger et al. 1991;Braun and Chase 1986;Byrnes et al. 1994;Delfs and Kelley 1990). Thus, in the context of behavioral sequencing, the simple 'repetitive' stereotypy (Berridge and Aldridge 2000a) produced by D2 receptor over-stimulation in the striatum (Delfs and Kelley 1990) can be seen as the inability to release one 'simple' behavior in order to allow initiation of the next simple behavior in a normal, adaptive sequence (Pedro et al. 1994;Szechtman et al. 1999). One means by which neuronal networks may interact within the striatum is via communication among clusters of functionally related striatal neurons. Such a network interaction may be mediated via gap junctions. It is well-established that electrotonic transmission between developing neurons is important in the formation and stabilization of functional networks (Bannerman et al. 2000;Peinado et al. 1993;Roerig and Feller 2000). However, there is also evidence that in the adult brain, electrotonic coupling directly mediates forms of neuronal network activity (Bou-Flores and Berger 2001;Jefferys 1995;Perez Velazquez and Carlen 2000) which, in turn, contribute to rhythmic behavioral patterning (Bou-Flores and Berger 2001;Rothwell 1998). Thus, it is likely that motor patterning may involve activity within neuronal networks coordinated via gap junctions. In the striatum, cells express connexins, the protein building blocks of gap junctions (Belluardo et al. 2000;Bennett et al. 1999). Striatal neurons also exhibit dye coupling, the transfer of dye molecules between neurons thro...

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Expression of Connexin36 in the adult and developing rat brain

Cited by 260 publications

References 49 publications

Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time

Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time

Intercellular interactions in the mammalian olfactory nerve

A Role for Electrotonic Coupling in the Striatum in the Expression of Dopamine Receptor-mediated Stereotypies,

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