Stimulus complexity dependent memory impairment and changes in motor performance after deletion of the neuronal gap junction protein connexin36 in mice

Frisch, Christian; Souza-Silva, M. A. De; Söhl, Goran; Güldenagel, Martin; Willecke, K.; Huston, Joseph P.; Dere, Ekrem

doi:10.1016/j.bbr.2004.06.023

Cited by 122 publications

(61 citation statements)

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“…Thus, in adults, oscillatory synchronization via weak gap junctional coupling at small gap junctions between LC neurons, together with norepinephrine actions on coupling in LC projection areas may contribute to the widespread influence of LC activity on behavioral state. In view of these considerations, deficits in LC neuronal gap junctional coupling may underlie some of the observed behavioral and neurological impairments in Cx36 KO mice (Hormuzdi et al, 2001;Frisch et al, 2005). Based on similar reasoning, the report of Cx32 and Cx26 localization in LC neurons might have suggested neurological impairments in human subjects with genetic abnormalities involving Cx26 and Cx32, whose clinical manifestations included sensorineural hearing loss (Kelsell et al, 1997) and peripheral neuropathy, respectively (Bergoffen et al, 1993;Bahr et al, 1999).…”

Section: Functional Implications Of Lc Neuronal Coupling and Gap Juncmentioning

confidence: 92%

Section: Published In Final Edited Form Asmentioning

confidence: 99%

“…In recent years, sensitive electrophysiological techniques have also documented electrical synapses in numerous adult brain regions (Bennett and Zukin, 2004); mRNA for the gap junction protein connexin36 (Cx36) was widely detected in neurons but not glia (Condorelli et al, 1998;Condorelli et al, 2000); and Cx36 was found to be present in ultrastructurally-defined gap junctions between neurons in many regions of both developing and adult CNS (Rash et al, 2001b;Nagy et al, 2004;Li et al, 2004a;Rash et al, 2005;Kamasawa et al, 2006;Fukuda et al, 2006). Moreover, the functional importance of Cx36 in adult brain is indicated by deficits in neuronal network properties and by behavioral impairments in Cx36 knockout mice (Hormuzdi et al, 2004;Frisch et al, 2005).Neurons of the locus coeruleus (LC) in rats have synchronized rhythmic electrical oscillations during early postnatal development, correlated with substantial electrical and dye-coupling between pairs of neurons (Christie et al, 1989;Christie and Jelinek, 1993;Oyamada et al, 1999;Andrzejewski et al, 2001;Ballantyne et al, 2004). In addition, synchronous electrical activity of LC neurons has been observed in slices from adult rats under conditions that indirectly support mediation of this activity by gap junctional coupling (Travagli et al, 1995;Ishimatsu and Williams, 1996;Alvarez et al, 2002).…”

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Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus

et al. 2007

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Locus coeruleus neurons are strongly coupled during early postnatal development, and it has been proposed that these neurons are linked by extraordinarily abundant gap junctions consisting of connexin32 and connexin26, and that those same connexins abundantly link neurons to astrocytes. Based on the controversial nature of those claims, immunofluorescence imaging and freeze-fracture replica immunogold labeling were used to re-investigate the abundance and connexin composition of neuronal and glial gap junctions in developing and adult rat and mouse locus coeruleus. In early postnatal development, connexin36 and Cx43 immunofluorescent puncta were densely distributed in the locus coeruleus, whereas connexin32 and connexin26 were not detected. By freeze-fracture replica immunogold labeling, connexin36 was found in ultrastructurally-defined neuronal gap junctions, whereas connexin32 and connexin26 were not detected in neurons and only rarely detected in glia. In 28-day postnatal (adult) rat locus coeruleus, immunofluorescence labeling for connexin26 was always co-localized with the glial gap junction marker connexin43; connexin32 was associated with the oligodendrocyte marker CNPase; and connexin36 was never co-localized with connexin26, Cx32 or connexin43. Ultrastructurally, connexin36 was localized to gap junctions between neurons, whereas connexin32 was detected only in oligodendrocyte gap junctions; and Cx26 was found only rarely in astrocyte junctions but abundantly in pia mater. Thus, in developing and adult locus coeruleus, neuronal gap junctions contain connexin36 but do not contain detectable connexin32 or connexin26, suggesting that the locus coeruleus has the same cell-type specificity of connexin expression as observed ultrastructurally in other regions of the central nervous system. Moreover, in both developing and adult locus coeruleus, no evidence was found for gap junctions or connexins linking neurons with astrocytes or oligodendrocytes, indicating that neurons in this nucleus are not linked to the pan-glial syncytium by connexin32-or connexin26-containing gap junctions or by abundant free connexons composed of those connexins. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 July 29. Published in final edited form as:Neuroscience. In the developing mammalian central nervous system (CNS), electrical coupling between neurons is well documented by electrophysiological and dye-coupling approaches (Peinado et al., 1993;Fulton, 1995;Montoro and Yuste, 2004;Bruzzone and...

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Section: Functional Implications Of Lc Neuronal Coupling and Gap Juncmentioning

confidence: 92%

Section: Published In Final Edited Form Asmentioning

confidence: 99%

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confidence: 99%

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Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus

et al. 2007

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“…An open-field test was performed between 5:00 and 7:00 pm using a rectangular chamber (l×w×h, 42×35×15 cm) that was divided into 30 squares of 7×7 cm and made of grey polyvinylchloride (PVC), as previously described (Frisch et al 2005;Dillon et al 2008). On the first day, the animals were placed in the open field and their locomotor activity was assessed.…”

Section: Open-field Habituationmentioning

confidence: 99%

Involvement of nitric oxide in improving stress-induced behavioural alteration by glatiramer acetate treatment in female BALB/c mice

et al. 2014

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“…Recently, Cx36 and Cx45 were identified as the predominant connexins expressed in adult neurons (9 -11). Deletion of either of the adult neuronal Cx genes, Cx36, or Cx45, results in deficiencies in signaling and transmission properties of neurons (12)(13)(14).…”

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confidence: 99%

Enhanced Neurite Outgrowth in PC12 Cells Mediated by Connexin Hemichannels and ATP

Belliveau

Bani‐Yaghoub

McGirr

et al. 2006

Journal of Biological Chemistry

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Gap junctions have traditionally been described as transmembrane channels that facilitate intercellular communication via the passage of small molecules. Connexins, the basic building blocks of gap junctions, are expressed in most mammalian tissues including the developing and adult central nervous system. During brain development, connexins are temporally and spatially regulated suggesting they play an important role in the proper formation of the central nervous system. In the current study, connexins 32 and 43 were overexpressed in PC12 cells to determine whether connexins are involved in neuronal differentiation. Both connexin 32 and 43 were appropriately trafficked to the cell membrane following overexpression and resulted in the formation of functional gap junctions. Connexin overexpression was found to cause enhanced neurite outgrowth in PC12 cells treated with nerve growth factor to initiate neuritogenesis. Surprisingly, however, enhanced neurite outgrowth was found to be the consequence of functional hemichannel formation as opposed to traditional intercellular communication. Additional analysis revealed that ATP was released into the media likely through hemichannels and acted on purinergic receptors to cause enhanced neurite outgrowth. Collectively, the results of the current study suggest that connexins may play an important role in neuronal differentiation by non-traditional mechanisms.

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Stimulus complexity dependent memory impairment and changes in motor performance after deletion of the neuronal gap junction protein connexin36 in mice

Cited by 122 publications

References 61 publications

Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus

Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus

Involvement of nitric oxide in improving stress-induced behavioural alteration by glatiramer acetate treatment in female BALB/c mice

Enhanced Neurite Outgrowth in PC12 Cells Mediated by Connexin Hemichannels and ATP

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