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Viral-mediated molecular and electrophysiological studies of connexin-36 function in models of neuronal connectivity
Ort / Verlag
ProQuest Dissertations & Theses
Erscheinungsjahr
2010
Quelle
ProQuest Dissertations & Theses A&I
Beschreibungen/Notizen
We have shown that Cx36 is differentially expressed during the differentiation of neuronal progenitor cells. Cx36 expression is abundant during embryogenesis and declines after birth, becoming restricted to subsets of neurons in the adult brain. Transduction of neuronal progenitor cells with Cx36 resulted in an increase in the percentage of cells expressing neuronal markers. Concurrently, RNAi studies show a decrease in neuronal cells. This may indicate a role for Cx36 in stem cell differentiation and neuronal fate. In the adult brain, Cx36 expression becomes restricted to subsets of neurons, in particular the parvalbumin-positive interneurons which have been shown to be involved in generating gamma-frequency oscillations. In neuronal networks, gap junction-mediated electrical coupling facilitates the generation of synchronized rhythmic activity and Cx36 KO mice show reduced gamma oscillations and display a number of cognitive deficits. In this study, Cx36 expression was manipulated by injection of the lentiviral vectors into the CA3 region of the hippocampus and field potential recordings of kainate-induced gamma oscillations were made. Other observations were made in the presence of 4-aminopyridine, GAP-134 and quinine. These data suggest that increasing Cx36 expression in the hippocampus improves neuronal network dynamics in the CA3 region by increasing the synchronous activity in the gamma frequency range. Our observations support previous studies suggesting that Cx36 is involved in the establishment of GJIC that regulates developmental and cellular signalling processes.