Dependence of rhythmic activity and oddball effects in the rat cortex on the depth of sedation during dissociative anesthesia.

The reactions to novelty manifesting in mismatch negativity in the rat brain were studied. During dissociative anesthesia, mismatch negativity-like waves were recorded from the somatosensory cortex using an epidural 32-electrode array. Experimental animals: 7 wild-type Wistar rats and 3 transgenic rats. During high-dose anesthesia, deviant 1,500 Hz tones were presented randomly among many standard 1,000 Hz tones in the oddball paradigm. "Deviant minus standard_before_deviant" difference waves were calculated using both the classical method of Naatanen and method of cross-correlation of sub-averages. Both methods gave consistent results: an early phasic component of the N40 and later N100 to 200 (mismatch negativity itself) tonic component. The gamma and delta rhythms power and the frequency of down-states (suppressed activity periods) were assessed. In all rats, the amplitude of tonic component grew with increasing sedation depth. At the same time, a decrease in gamma power with a simultaneous increase in delta power and the frequency of down-states. The earlier phasic frontocentral component is associated with deviance detection, while the later tonic one over the auditory cortex reflects the orienting reaction. Under anesthesia, this slow mismatch negativity-like wave most likely reflects the tendency of the system to respond to any influences with delta waves, K-complexes and down-states, or produce them spontaneously.

Theta Bursts Precede, and Spindles Follow, Cortical and Thalamic Downstates in Human NREM Sleep.

Since their discovery, slow oscillations have been observed to group spindles during non-REM sleep. Previous studies assert that the slow-oscillation downstate (DS) is preceded by slow spindles (10-12 Hz) and followed by fast spindles (12-16 Hz). Here, using both direct transcortical recordings in patients with intractable epilepsy (n = 10, 8 female), as well as scalp EEG recordings from a healthy cohort (n = 3, 1 female), we find in multiple cortical areas that both slow and fast spindles follow the DS. Although discrete oscillations do precede DSs, they are theta bursts (TBs) centered at 5-8 Hz. TBs were more pronounced for DSs in NREM stage 2 (N2) sleep compared with N3. TB with similar properties occur in the thalamus, but unlike spindles they have no clear temporal relationship with cortical TB. These differences in corticothalamic dynamics, as well as differences between spindles and theta in coupling high-frequency content, are consistent with NREM theta having separate generative mechanisms from spindles. The final inhibitory cycle of the TB coincides with the DS peak, suggesting that in N2, TB may help trigger the DS. Since the transition to N1 is marked by the appearance of theta, and the transition to N2 by the appearance of DS and thus spindles, a role of TB in triggering DS could help explain the sequence of electrophysiological events characterizing sleep. Finally, the coordinated appearance of spindles and DSs are implicated in memory consolidation processes, and the current findings redefine their temporal coupling with theta during NREM sleep.SIGNIFICANCE STATEMENT Sleep is characterized by large slow waves which modulate brain activity. Prominent among these are downstates (DSs), periods of a few tenths of a second when most cells stop firing, and spindles, oscillations at ∼12 times a second lasting for ∼a second. In this study, we provide the first detailed description of another kind of sleep wave: theta bursts (TBs), a brief oscillation at ∼six cycles per second. We show, recording during natural sleep directly from the human cortex and thalamus, as well as on the scalp, that TBs precede, and spindles follow DSs. TBs may help trigger DSs in some circumstances, and could organize cortical and thalamic activity so that memories can be consolidated during sleep.

Altered striatal rhythmic activity in cylindromatosis knock-out mice due to enhanced GABAergic inhibition.

Despite the highest expression in striatum, physiological function of cylindromatosis (CYLD), a deubiquitinating enzyme, remains unexplored. We found, in the present study, that the duration of spontaneous up-states in the striatum is shorter and membrane potential fluctuation preceding action potential and firing rate are increased in Cyld(-/-) mice. Excess striatal GABAergic inhibition likely plays the major role in this alteration as supported by the findings: (1) the levels of striatal GABAA and GABAB receptors in Cyld(-/-) mice are increased, (2) pharmacological blockade of GABAB receptors rescues the shortened up-state phenotype, and (3) pharmacological blockade of GABAA receptors rescues the power of beta frequency oscillations. Our results indicate that CYLD alters striatal network function by regulating the protein expression levels of GABA receptors.

Sevoflurane-induced loss of consciousness is paralleled by a prominent modification of neural activity during cortical down-states.

Networks of neocortical neurons display a bistable activity pattern characterised by phases of high frequency action potential firing, so called up-states, and episodes of low discharge activity (down-states). We hypothesised that during down-states neocortical neurons are vulnerable to anaesthetic agents. To tackle this issue, it is necessary to identify analytical methods, which are sufficiently sensitive for resolving anaesthetic effects during phases of scarce neuronal activity. The local field potential was recorded in organotypic cultures (OTC) from rat neocortex under control conditions and in the presence of increasing concentrations of sevoflurane by extracellular electrodes. Epochs from down-states were cut from the local field potential and analysed using power spectrum density as well as non-linear parameters approximate entropy (ApEn) and order recurrence rate (ORR). ApEn and ORR proved to be suitable tools for analysing the actions of volatile anaesthetics on cortical down-states. During these phases of low neuronal activity, sevoflurane caused prominent changes in the local field potential. Time series analysis using ApEn showed a reduction of signal predictability in the presence of sevoflurane. Furthermore, the ORR displayed an abrupt decrease at sevoflurane concentrations corresponding to loss of consciousness in vivo, indicating a drug-induced decrease in the signal to noise ratio. The actions of volatile anaesthetics on cortical down-states have been neglected so far, perhaps due to the lack of suitable analysis tools. In the current in vitro study the non-linear parameters ApEn and ORR are introduced to characterise volatile anaesthetics actions. Sevoflurane alters cortical down-states as indicated by non-linear parameter analysis of local field potential recording from cultured neuronal networks. ORR even displays an abrupt change, i.e., a step-like behaviour indicating an increased signal complexity at concentrations of sevoflurane corresponding to loss of consciousness in humans.