theta (4-12 Hz) and gamma (40-90) oscillations are prominent rhythms in the mammalian brain. A striking feature of these rhythms, possibly vital to memory encoding, is their specific coordination in a manner that has been termed 'nesting', i.e. the preferred occurrence of bouts of gamma activity during specific phases of theta. Both rhythms are shaped by the neuromodulator acetylcholine, but it is unknown to what degree their coordination is influenced by cholinergic neuromodulation. Here, we investigated the effects of a blockade of muscarinic acetylcholine receptors by atropine on theta and gamma oscillations, and their interaction, in mouse hippocampus in vivo. Multi-site recordings from area CA1 of freely moving mice showed that under control conditions gamma activity was amplitude-modulated at theta frequencies. This coordination of theta and gamma oscillations, as assessed by cross-correlation of theta with the gamma envelope, was prominent in basal and apical dendritic laminae but not in intermediate laminae. It was stronger during active exploration than during awake immobility. Atropine (50 mg/kg intraperitoneal) altered several aspects of the individual and nested rhythms. It rendered theta activity irregular, decreased theta oscillation frequency and reduced gamma power. Atropine also reduced the amplitude-modulation of gamma oscillations at theta frequencies, in part by perturbing the coordination of the rhythms on a short time scale. Thus, our findings demonstrate that phase locking of the amplitude of gamma oscillations to theta in hippocampal area CA1 is partially governed by neuronal elements harbouring muscarinic receptors.

Background-Temporary, antegrade amnesia is one of the core desirable endpoints of general anesthesia. Multiple lines of evidence support a role for the hippocampal θ-rhythm, a synchronized rhythmic oscillation of field potentials at 4-12 Hz, in memory formation. Previous studies have revealed a disruption of the θ-rhythm at surgical levels of anesthesia. We hypothesized that modulation of θ-rhythm would also occur at subhypnotic but amnestic concentrations. Therefore we examined the effect of three inhaled agents on properties of the θ-rhythm that are considered to be critical for the formation of hippocampus-dependent memories.

Background The intravenous delivery of halogenated volatile anesthetics has been previously achieved using phospholipid-stabilized emulsions, e.g. Intralipid. However, fluorinated volatile anesthetics, such as sevoflurane, are partially fluorophilic and do not mix well with classic non-fluorinated lipids. This effect limits the maximum amount of sevoflurane that can be stably emulsified in Intralipid to 3.5% v/v. This is a significant limitation to the potential clinical use of Intralipid-based emulsions. Methods The authors prepared a 20% v/v sevoflurane emulsion using a novel fluorinated surfactant and tested its effectiveness and therapeutic index by administering it to male Sprague-Dawley rats via intravenous injection into the jugular vein. The median effective dose to induce anesthesia (ED50), median lethal dose (LD50), and therapeutic index (LD50 / ED50) were determined. Anesthesia was measured by loss of the forepaw righting reflex. Results The ED50 and LD50 values were found to be 0.41 and 1.05 mL emulsion / kg body weight, respectively. These lead to a therapeutic index of 2.6, which compares favorably to previously determined values of emulsified isoflurane, as well as values for propofol and thiopental. Conclusions A novel semi-fluorinated surfactant was able to considerably increase the maximum amount of stably emulsified sevoflurane compared to Intralipid. These formulations can be used to rapidly induce anesthesia with bolus dosing from which recovery is smooth and rapid.

RA. Altered GABA A,slow inhibition and network oscillations in mice lacking the GABA A receptor ␤ 3 subunit.

Drug-induced changes in theta oscillations may be a common basis for amnesia produced by F6 and isoflurane. The different patterns suggest that these drugs alter network activity by acting on different molecular and/or cellular targets.