Selective impairment of hippocampal gamma oscillations in connexin-36 knock-out mouse in 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.

Fig. 1.

Ripples are not affected by deletion of CX36 gap junction. A, Examples of ripple episodes (1.0 Hz to 3 kHz) in representative WT and Cx36 KO animals (top traces). Averaged ripples for the two mice. Mean ± SEM.B, Comparison of ripple power between WT and Cx36 KO animals. Averaged power spectra for all mice in the respective groups (mean ± SEM) during slow-wave sleep (5–10 min sessions). Note similarly increased power between 100 and 200 Hz, corresponding to ripple power in both groups. Inset, Power of isolated ripple episodes (7 SD above background mean; see Materials and Methods). Note similar peak frequency and power in both groups.

Fig. 2.

Gamma power is impaired in Cx36 KO mice. Group mean ± SEM power spectra for KO and WT mice during REM sleep (A) and wheel running (B) sessions. Note large difference in power for frequencies >20 Hz.

Fig. 3.

Phase modulation of gamma amplitude in the theta cycle. A, B, Top traces, Grand mean theta waves (1 Hz to 3 kHz) from WT (thick line) and KO (thin line) mice. Two cycles are shown for clarity. A, Instantaneous gamma amplitude (root mean square power) as a function of theta phase during REM sleep. Note largest gamma amplitude after the theta peak. B, Comparison during wheel running. Note larger mean power of gamma oscillation in WT. Note also that the difference between KO and WT groups is larger at theta peak than at theta trough.

Fig. 4.

Theta phase and unit activity. A, Pyramidal cells (pyr) (WT, n= 31 neurons; KO, n = 50). B, Interneurons (int) (WT, n = 21; KO,n = 34). A, Top traces, Grand mean theta waves (1 Hz to 3 kHz) from WT (thick line) and KO (thin line) mice, combined from REM and wheel running sessions. Graphs shows mean ± SEM.