Akihiro Karashima

Theta wave amplitude and frequency are differentially correlated with pontine waves and rapid eye movements during REM sleep in rats.

The present study examined the correlations between the dynamics of hippocampal theta waves and pontine waves (P waves) and rapid eye movements (REMs) densities during REM sleep. Theta wave peak frequency and theta amplitude were estimated as the parameters of theta wave dynamics in each 3s segment. The peak frequency and theta amplitude were positively correlated with P wave and REMs densities, however their detailed correlation properties were distinct from each other. Dependency of peak frequency on P wave/REMs density did not change significantly from that on REMs/P wave density. On the other hand, dependency of the theta amplitude on P wave/REMs density significantly increased with an increased REMs/P wave density. Because hippocampal theta waves and P waves are involved in learning and memory functions during REM sleep, the correlation between theta parameters and P wave density might help to clarify these functions.

Instantaneous acceleration and amplification of hippocampal theta wave coincident with phasic pontine activities during REM sleep

Rapid eye movement (REM) sleep is characterized by hippocampal theta waves and phasic spike-like waves originating from the pons, termed ponto-geniculo-occipital (PGO) waves in cats and pontine (P) waves in rats. While the theta wave and PGO/P wave have been suggested to participate in higher-order brain functions, their generation mechanisms and roles in brain functions have been studied independently. Therefore, the present study investigated instantaneous aspects of the relationship between theta waves and PGO/P waves in both cats and rats. Theta wave was instantaneously accelerated several hundred milliseconds before the negative peak of the PGO/P wave in both animals, and was also amplified just before PGO/P wave occurrence. Considering the integrated knowledge provided by studies of both animals, these results suggest that PGO/P wave-related activities in the pons are delivered to the theta wave generator. The activations of the theta wave coincident with PGO/P wave might facilitate cooperative contribution to higher-order brain functions in REM sleep.

Phase-locking of spontaneous and elicited ponto-geniculo-occipital waves is associated with acceleration of hippocampal theta waves during rapid eye movement sleep in cats.

We investigated the temporal relationship between hippocampal theta waves and ponto-geniculo-occipital waves (PGO) during rapid eye movement sleep (REM sleep) in cats. In addition, we analyzed the relationship between hippocampal theta waves and PGO as elicited by tone stimulus (PGO(E)) in order to quantitively characterize the PGO wave generator mechanism. The results showed that a spontaneous PGO tended to be phase-locked to the theta wave, which was more clearly observed in the single PGO than in the cluster. However, cluster PGO(E) tended to be phase-locked as well as single PGO(E). It was therefore suggested that the generator of PGO is activated in relation to the hippocampal theta wave. An acceleration of the theta wave associated with PGO occurrence was found, and was more markedly observed than with the cluster PGO. Although the magnitude of it was less than in the spontaneous case, an acceleration around the PGO(E) was also observed. These results suggest that the generators of theta and PGO receive some common activations, especially when a cluster PGO is generated. The interaction between PGO and hippocampal theta waves is expected to be involved in the possible functions of REM sleep.

Enhancement of Synchronization Between Hippocampal and Amygdala Theta Waves Associated With Pontine Wave Density

Theta waves in the amygdala are known to be synchronized with theta waves in the hippocampus. Synchronization between amygdala and hippocampal theta waves is considered important for neuronal communication between these regions during the memory-retrieval process. These theta waves are also observed during rapid eye movement (REM) sleep. However, few studies have examined the mechanisms and functions of theta waves during REM sleep. This study examined correlations between the dynamics of hippocampal and amygdala theta waves and pontine (P) waves in the subcoeruleus region, which activates many brain areas including the hippocampus and amygdala, during REM sleep in rats. We confirmed that the frequency of hippocampal theta waves increased in association with P wave density, as shown in our previous study. The frequency of amygdala theta waves also increased with in associated with P wave density. In addition, we confirmed synchronization between hippocampal and amygdala theta waves during REM sleep in terms of the cross-correlation function and found that this synchronization was enhanced in association with increased P wave density. We further studied theta wave synchronization associated with P wave density by lesioning the pontine subcoeruleus region. This lesion not only decreased hippocampal and amygdala theta frequency, but also degraded theta wave synchronization. These results indicate that P waves enhance synchronization between regional theta waves. Because hippocampal and amygdala theta waves and P waves are known to be involved in learning and memory processes, these results may help clarify these functions during REM sleep.

Phase-locking of spontaneous and tone-elicited pontine waves to hippocampal theta waves during REM sleep in rats

Temporal relationships between hippocampal theta waves and pontine waves (P waves) during rapid-eye-movement (REM) sleep were investigated in rats. P waves were phase-locked to the positive theta peak. The phase relationships of P waves elicited by a tone stimulus (P(E) waves) to hippocampal theta waves were also analyzed to qualitatively clarify the mechanism of phase-locking between these two phenomena. P(E) waves occurred at the positive theta peak, as seen for spontaneous P waves. This phase preference of P(E) waves could be understood as that of the response probability to tone stimulus. These data suggest that the P-wave generator receives inputs that mimic theta waves. As hippocampal theta waves and P waves are known to be involved in learning and memory processes during REM sleep, the present studies could help to clarify these functions.

Mathematical models of regulatory mechanisms of sleep-wake rhythms

Abstract.Studies of regulatory mechanisms of sleep-wake rhythms have benefited greatly from mathematical modeling. There are two major frameworks of modeling: one integrates homeostatic and circadian regulations and the other consists of multiple interacting oscillators. In this article, model constructions based on these respective frameworks and their characteristics are reviewed. The two-process model and the multioscillator model are explained in detail. An appropriate mathematical abstraction is also shown to provide a viewpoint unifying the model structures, which might seem to be distinct. Recently acquired knowledge of neural regulatory mechanisms of sleep-wake rhythm has prompted modeling at the neural network level. Such a detailed model is also reviewed, and could be used to explore a possible neural mechanism underlying a pathological state of sleep-wake rhythm.

Synchronization between hippocampal theta waves and PGO waves during REM sleep

We investigated the temporal relationship between hippocampal theta waves (referred to as ‘theta waves’) and ponto‐geniculo‐occipital (PGO) waves in cats. We measured the time intervals between an occurrence of a PGO wave and the prior and posterior adjacent positive peaks of the theta wave. The unimodal distributions of these intervals suggested a close temporal relationship between PGO and theta waves (i.e. synchronization). In addition, the period of a theta wave during which a PGO wave occurred was not statistically different from that without a PGO wave. This result suggests that the synchronization found here is characterized by phase‐locking rather than phase‐resetting. Common mechanisms are suggested to underlie the generation of PGO and theta waves.

Multi-neuron action potentials recorded with tetrode are not instantaneous mixtures of single neuronal action potentials

Multiunit recording with multi-site electrodes in the brain has been widely used in neuroscience studies. After the data recording, neuronal spikes should be sorted according to the pattern of spike waveforms. For the spike sorting, independent component analysis (ICA) has recently been used because ICA has potential for resolving the problem to separate the overlapped multiple neuronal spikes. However the performance of spike sorting by using ICA has not been examined in detail. In this study, we quantitatively evaluate the performance of ICA-based spike sorting method by using simulated multiunit signals. The simulated multiunit signal is constructed by compositing real extracellular action potentials recorded from guinea-pig brain. It is found that the spike sorting by using ICA hardly avoids significant false positive and negative errors due to the cross-talk noise contamination on the separated signals. The cross-talk occurs when the multiunit signal of each recording channel have significant time difference; this situation does not satisfy the assumption of instantaneous source mixture for the major ICA algorithms. Since the channel delay problem is hardly resolved, an ICA algorithm which does not require the instantaneous source mixing assumption would be appropriate for use of spike sorting.

The 3D position estimation of neurons in the hippocampus based on the multi-site multi-unit recordings with silicon tetrodes

The mechanical strain of the neural tissue induced by the implant of neuronal electrode is one of the important factors responsible for the quality and performance of extracellular recording of neuronal activities in the brain because the mechanical strain could kill or inactivate the neurons. In order to evaluate the effect of the implant of neural electrode, we propose a method to estimate the three-dimensional distribution of electrophysiologically active neurons near the electrode based on the multi-site multi-unit recording data. The spatial distribution of the active neurons emerges the region in the neural tissue that could be killed or inactivated by the implant of the electrode. The proposed method will be useful for the in situ assessment of the neural electrode implanted in the brain.The mechanical strain of the neural tissue induced by the implant of neuronal electrode is one of the important factors responsible for the quality and performance of extracellular recording of neuronal activities in the brain because the mechanical strain could kill or inactivate the neurons. In order to evaluate the effect of the implant of neural electrode, we propose a method to estimate the three-dimensional distribution of electrophysiologically active neurons near the electrode based on the multi-site multi-unit recording data. The spatial distribution of the active neurons emerges the region in the neural tissue that could be killed or inactivated by the implant of the electrode. The proposed method will be useful for the in situ assessment of the neural electrode implanted in the brain.

Modeling of segmentation clock mechanism in presomitic mesoderm

Somite is sequentially generated in a head-to-tail order by segmentation of the mesenchymal tissue called presomitic mesoderm (PSM). The segmentation occurs periodically at the anterior end of the PSM, and this periodic segmentation has been suggested to be regulated by a molecular clock. In mouse PSM, the segmentation-related genes change their expression every 120 minutes, and this cyclic expression is essential for regular somite segmentation. In this study, a molecular mechanism of segmentation clock involving Wnt and Delta-Notch signaling pathways is modeled, and reality of the model structure is investigated through simulating biological findings. One dimensional array of the cellular clock models is constructed to simulate spatio-temporal dynamics of the gene-expressions in the PSM. The simulation result suggests that the Wnt gradient across the PSM is involved in the dynamics under concern.