Selective Impairment of Hippocampal Gamma Oscillations in Connexin-36 Knock-Out MouseIn Vivo

Abstract

The physiological roles of neuronal gap junctions in the intact brain are not known. The recent generation of the connexin-36 knock-out (Cx36 KO) mouse has offered a unique opportunity to examine this problem. Recent in vitro recordings in Cx36 KO mice suggested that Cx36 gap junction contributes to various oscillatory patterns in the theta (approximately 5-10 Hz) and gamma (approximately 30-80 Hz) frequency ranges and affects certain aspects of high-frequency (>100 Hz) patterns. However, the relevance of these pharmacologically induced patterns to the intact brain is not known. We recorded field potentials and unit activity in the CA1 stratum pyramidale of the hippocampus in the behaving wild-type (WT) and Cx36 KO mice. Fast-field "ripple" oscillations (140-200 Hz) were present in both WT and KO mice and did not differ significantly in power, intraepisode frequency, or probability of occurrence. Thus, fast-field oscillations either may not require electrical synapses or may be mediated by a hitherto unknown class of gap junctions. Theta oscillations, recorded during either wheel running or rapid eye movement sleep, were not different either. However, the power in the gamma frequency band and the magnitude of theta-phase modulation of gamma power were significantly decreased in KO mice compared with WT controls during wheel running. This suggests that Cx36 interneuronal gap junctions selectively contribute to gamma oscillations.

Hippocampal theta rhythm and its coupling with gamma oscillations require fast inhibition onto parvalbumin-positive interneurons

“…In control mice gamma oscillations were strongly modulated within the theta cycle with amplitude of gamma oscillation being highest briefly after the peak of the theta cycle (Ϸ20 o ), as reported in rodents for CA1 stratum pyramidale (6,8,38). This coupling between theta and gamma oscillations was severely disrupted in PV-⌬␥ 2 mice (Fig.…”

Functional Properties of Electrical Synapses Between Inhibitory Interneurons of Neocortical Layer 4

“…Consistent with this, experiments on neocortical slices have shown the importance of electrical synapses among inhibitory neurons for synchronous network activity (Beierlein et al 2000;Deans et al 2001;Galarreta and Hestrin 2001;Tamas et al 2000). Recent work in connexin36 (Cx36) knockout mice supports a role for electrically coupled inhibitory neurons in gamma oscillations in the hippocampus (Buhl et al 2003;Hormuzdi et al 2001). Theoretical studies demonstrate that, in principle, an inhibitory network interconnected by both chemical and electrical synapses can produce synchronous network activity (Bartos et al 2002; Golomb and Rinzel 1993;Pfeuty et al 2003;Traub et al 2001;van Vreeswijk et al 1994;Wang and Buzsaki 1996;White et al 1998).…”

Gap junctions on hippocampal mossy fiber axons demonstrated by thin-section electron microscopy and freeze–fracture replica immunogold labeling

“…We predict that if gap junctions can be eliminated from the hippocampal MF axons in a knockout mouse, then the dentate gyrus in such animals would not exhibit very high-frequency oscillations in media with elevated external K ϩ ion concentration and decreased external Ca 2ϩ ion concentration. Interestingly, very fast oscillations were unaffected in mice lacking Cx36 (32,33), suggesting that gap junction proteins in addition to Cx36 may contribute to the formation of axoaxonic gap junctions. On the other hand, another study has reported a decreased incidence of in vitro high-frequency ripples in a Cx36 knockout mouse (34).…”