Spindle Bursts Research Articles

Cholinergic Control in Developing Prefrontal–Hippocampal Networks

The cholinergic drive enhances input processing in attentional and mnemonic context by interacting with the activity of prefrontal-hippocampal networks. During development, acetylcholine modulates neuronal proliferation, differentiation, and synaptic plasticity, yet its contribution to the maturation of cognitive processing resulting from early entrainment of neuronal networks in oscillatory rhythms remains widely unknown. Here we show that cholinergic projections growing into the rat prefrontal cortex (PFC) toward the end of the first postnatal week boost the generation of nested gamma oscillations superimposed on discontinuous spindle bursts by acting on functional muscarinic but not nicotinic receptors. Although electrical stimulation of cholinergic nuclei increased the occurrence of nested gamma spindle bursts by 41%, diminishment of the cholinergic input by either blockade of the receptors or chronic immunotoxic lesion had the opposite effect. This activation of locally generated gamma episodes by direct cholinergic projections to the PFC was accompanied by indirect modulation of underlying spindle bursts via cholinergic control of hippocampal theta activity. With ongoing maturation and switch of network activity from discontinuous bursts to continuous theta-gamma rhythms, accumulating cholinergic projections acting on both muscarinic and nicotinic receptors mediated the transition from high-amplitude slow to low-amplitude fast rhythms in the PFC. By exerting multiple actions on the oscillatory entrainment of developing prefrontal-hippocampal networks, the cholinergic input may refine them for later gating processing in executive and mnemonic tasks.

Neocortical Activation of the Hippocampus during Sleep in Infant Rats

We recently reported that the majority of hippocampal neurons in newborn rats increase their activity in association with myoclonic twitches, which are indicative of active sleep. Because spindle bursts in the developing somatosensory neocortex occur in response to sensory feedback from myoclonic twitching, we hypothesized that the state-dependent activity of the newborn hippocampus arises from sensory feedback that sequentially activates the neocortex and then hippocampus, constituting an early form of neocortical-hippocampal communication. Here, in unanesthetized 5- to 6-d-old rats, we test this hypothesis by recording simultaneously from forelimb and barrel regions of somatosensory neocortex and dorsal hippocampus during periods of spontaneous sleep and wakefulness and in response to peripheral stimulation. Myoclonic twitches were consistently followed by neocortical spindle bursts, which were in turn consistently followed by bursts of hippocampal unit activity; moreover, spindle burst power was positively correlated with hippocampal unit activity. In addition, exogenous stimulation consistently evoked this neocortical-to-hippocampal sequence of activation. Finally, parahippocampal lesions that disrupted functional connections between the neocortex and hippocampus effectively disrupted the transmission of both spontaneous and evoked neocortical activity to the hippocampus. These findings suggest that sleep-related motor activity contributes to the development of neocortical and hippocampal circuits and provides a foundation on which coordinated activity between these two forebrain structures develops.

Developmental appearance and disappearance of cortical events and oscillations in infant rats

Until recently, organized and state-dependent neocortical activity in infant rats was thought to commence with the emergence of delta waves at postnatal day (P)11. This view is changing with the discovery of several forms of cortical activity that are detectible soon after birth, including spindle bursts (SBs) and slow activity transients (SATs). Here we provide further evidence of surprisingly rich cortical activity patterns during early development and document, in P5–P13 rats, the appearance, disappearance, and transient expression of three cortical events and oscillations. EEG activity in frontal, parietal, and occipital cortices was recorded in unanesthetized, head-fixed subjects using 16-channel laminar silicon electrodes and Ag–AgCl electrodes. In addition to SATs, we identified two novel forms of activity: cortical sharp potentials (CSPs) and gamma bursts (GBs). SBs were not observed in these areas. CSPs, defined as discrete, biphasic events with a duration of 250 ms, exhibited an inverted-U developmental trajectory with peak prevalence at P9. In contrast, GBs, defined as brief bursts of 40-Hz activity, increased steadily in prevalence and duration from P5 through P13. The prevalence of SATs decreased steadily across the ages tested here. Furthermore, both CSPs and GBs were more likely to occur during sleep than during wakefulness. Because SATs, CSPs, and GBs exhibit different developmental trajectories and rates of occurrence, and can occur independently of each other, they appear to be distinct patterns of neuronal activity. We hypothesize that these diverse patterns of neurophysiological activity reflect the instantaneous local structure and connectivity of the developing neocortex.

An abrupt developmental shift in callosal modulation of sleep-related spindle bursts coincides with the emergence of excitatory-inhibitory balance and a reduction of somatosensory cortical plasticity.

Transecting the corpus callosum of postnatal day (P)1-6 rats disinhibits the production of spindle bursts (SBs) within primary somatosensory cortex (S1), most notably during periods of sleep-related myoclonic twitching. Here we investigated developmental changes in this callosally mediated disinhibition and its association with cortical plasticity. Recordings in P2-15 subjects revealed that callosotomy-induced disinhibition is a transient feature of early development that disappears abruptly after P6. This abrupt switch was accompanied by sharp decreases in myoclonic twitching and equally sharp increases in spontaneous SBs and in the number of GABAergic and glutamatergic presynaptic terminals in S1. Expression of the K+Cl- cotransporter 2 (KCC2) also increased across these ages. To determine whether these developmental changes are associated with alterations in cortical plasticity, pups were callosotomized at P1, P6, or P8, and tested over the subsequent week. Regardless of age, callosotomy immediately disrupted SBs evoked by forepaw stimulation. Over the next week, the P1 and P6 callosotomy groups exhibited full recovery of function; in contrast, the P8 group did not exhibit recovery of function, thus indicating an abrupt decrease in cortical plasticity between P6 and P8. Together, our data demonstrate that callosotomy-induced disinhibition is a transient phenomenon whose disappearance coincides with the onset of increased intrinsic connectivity, establishment of excitatory-inhibitory balance, and diminished plasticity in S1. Accordingly, our findings indicate that callosotomy-induced disinhibition of twitch-related SBs is a bioassay of somatosensory cortical plasticity and, in addition, support the hypothesis that myoclonic twitches, like retinal waves, actively contribute to cortical development and plasticity.

Early Development of the Thalamic Inhibitory Feedback Loop in the Primary Somatosensory System of the Newborn Mice

Spontaneous neuronal activity plays an important role during the final development of the brain circuits and the formation of the primary sensory maps. In young rats, spindle bursts have been recorded in the primary somatosensory cortex. They are correlated with spontaneous muscle twitches and occur before active whisking. They bear similarities with the spindles recorded in adult brain that occur during early stages of sleep and rely on a thalamic feedback loop between the glutamatergic nucleus ventroposterior medialis (nVPM) and the GABAergic nucleus reticularis thalami (nRT). However, whether a functional nVPM-nRT loop exists in newborn rodents is unknown. We studied the reciprocal synaptic connections between nVPM and nRT in thalamic acute slices from mice from birth [postnatal day 0 (P0)] until P9. We first demonstrated that nVPM-to-nRT EPSCs could be distinguished from corticothalamic EPSCs by their inhibition by 5-HT attributable to the transient expression of functional presynaptic serotonin 1B receptors. The nVPM-to-nRT EPSCs and nRT-to-nVPM IPSCs were both detected the first day after birth; their amplitude near 2 nS was relatively stable until P5. At P6-P7, there was a rapid and simultaneous increase of both nVPM-to-nRT EPSCs and nRT-to-nVPM IPSCs that reached 8 and 9 nS, respectively. Our results show that the thalamic synapses implicated in spindle activity are functional shortly after birth, suggesting that they could already generate spindles during the first postnatal week. Our results also suggest an inhibitory action of 5-HT on the spindle bursts of the newborn mice.

Three Patterns of Oscillatory Activity Differentially Synchronize Developing Neocortical Networks In Vivo

Coordinated patterns of electrical activity are important for the early development of sensory systems. The spatiotemporal dynamics of these early activity patterns and the role of the peripheral sensory input for their generation are essentially unknown. We performed extracellular multielectrode recordings in the somatosensory cortex of postnatal day 0 to 7 rats in vivo and observed three distinct patterns of synchronized oscillatory activity. (1) Spontaneous and periphery-driven spindle bursts of 1-2 s in duration and approximately 10 Hz in frequency occurred approximately every 10 s. (2) Spontaneous and sensory-driven gamma oscillations of 150-300 ms duration and 30-40 Hz in frequency occurred every 10-30 s. (3) Long oscillations appeared only every approximately 20 min and revealed the largest amplitude (250-750 microV) and longest duration (>40 s). These three distinct patterns of early oscillatory activity differently synchronized the neonatal cortical network. Whereas spindle bursts and gamma oscillations did not propagate and synchronized a local neuronal network of 200-400 microm in diameter, long oscillations propagated with 25-30 microm/s and synchronized 600-800 microm large ensembles. All three activity patterns were triggered by sensory activation. Single electrical stimulation of the whisker pad or tactile whisker activation elicited neocortical spindle bursts and gamma activity. Long oscillations could be only evoked by repetitive sensory stimulation. The neonatal oscillatory patterns in vivo depended on NMDA receptor-mediated synaptic transmission and gap junctional coupling. Whereas spindle bursts and gamma oscillations may represent an early functional columnar-like pattern, long oscillations may serve as a propagating activation signal consolidating these immature neuronal networks.

The corpus callosum modulates spindle‐burst activity within homotopic regions of somatosensory cortex in newborn rats

The corpus callosum, a major interhemispheric fiber tract, mediates communication between homotopic regions within the primary somatosensory cortex (S1). Recently, in 1- to 6-day-old rats, brief bursts of oscillatory activity - called spindle-bursts (SBs) - were described in cortical somatosensory areas following sensory feedback from sleep-related myoclonic twitches or specific peripheral stimulation. To determine whether interhemispheric communication via the corpus callosum modulates the expression of SBs during this early period of development, we investigated the spontaneous expression of SBs in unanesthetized 1- to 6-day-old rats as well as SBs evoked by plantar surface stimulation of the forepaw. We hypothesized that surgically disrupting transcallosal communication (i.e. with callosotomy) or unilateral pharmacological manipulation of S1 activity (e.g. by blocking muscarinic receptors) would alter S1 activity in one or both hemispheres. First, callosotomy doubled the rate of spontaneous, twitch-related SBs in left and right S1s by reducing the interval between successive SBs. Second, unilateral infusion into the left S1 of the muscarinic receptor antagonist, scopolamine, inhibited SBs in response to right forepaw stimulation; importantly, SBs were now disinhibited in the right S1 to right forepaw stimulation, thus 'unmasking' an ipsilateral representation. Subsequent callosotomy reinstated contralateral SB responses in the left S1. Finally, tactile and proprioceptive stimulation produced dissociable neurophysiological S1 responses; specifically, SBs were produced in response to proprioceptive, but not tactile, stimulation. We conclude that the corpus callosum modulates functionally inhibitory interactions between homotopic regions in left and right S1s during the early developmental period when organized neurophysiological activity is first detected in the neocortex.

NMDA Receptors Pattern Early Activity in the Developing Barrel Cortex In Vivo

N-methyl-D-aspartate (NMDA) type of glutamate receptors play an important role in activity-dependent plasticity in the developing cortex. However, the physiological patterns of cortical activity that activate NMDA receptors in vivo remain largely unknown. We performed full-band recordings from the barrel cortex of neonatal rats in vivo and found that the dominant pattern of the early activity, network driven spindle bursts, are associated with large amplitude NMDA receptor-dependent delta waves. The major sink of delta waves was in the dense cortical plate, which coincided with the sinks of sensory-evoked responses as well as fast spindle-burst oscillations. Pharmacological analysis revealed major contributions from NMDA and alpha-aminopropionate (AMPA) type of glutamate receptors in the generation of delta waves, whereas fast oscillations primarily involved only AMPA receptors. Our results suggest that the 2 component spindle burst is generated by rhythmic, presumably thalamocortical, synaptic input which entrains an AMPA receptor-mediated fast oscillation and who's summation generates an NMDA and AMPA receptor mediated delta wave. The massive summation of thalamocortical activity during the spindle bursts thus provides a long time window for co-incident activation of cortical neurons by the thalamocortical cells which may contribute to the formation of thalamocortical synapses in the barrel cortex during the critical period of developmental plasticity.

Relationships Between Sleep Spindles and Activities of Cerebral Cortex as Determined by Simultaneous EEG and MEG Recording

The purpose of this study was to clarify the relationships between the distributions and cortical sources of two types of spindles in the magnetoencephalogram (MEG) and how cortical activating areas contribute to the distribution of spindles. Spontaneous activities during sleep stage 2 were recorded from 7 normal subjects by simultaneous EEG and MEG recordings. Two types of spindles with frequency-specific topographic differences (fast spindles and slow spindles) were defined by EEG, and, subsequently, the sources of spindles were estimated as equivalent current dipoles using MEG. Activation centered in four areas, the precentral and postcentral areas in posterior frontal cortex and parietal cortex of each hemisphere. However, these areas were not always activated simultaneously. Fast spindles were associated with more frequent activation of postcentral areas with stronger activation strengths, whereas slow spindles were associated with more frequent activation of precentral areas with stronger activation strengths. When spindles were distributed symmetrically in amplitude between the hemispheres on both EEG and MEG, the four areas were activated equally and simultaneously. When spindles exhibited asymmetric distributions with amplitude differences above 30% between hemispheres, the cortical areas were activated with variable temporal relationships. Two types of spindle oscillations observed in the MEG had a common neural basis at the cortical level, with variability in patterns of activation and activation strengths resulting in the differences in distribution observed on the EEG and MEG. The differences in cortical activation patterns and activation strengths between the two types of spindles suggest that two distinct forms of spindle bursts propagate to cortex through different underlying neuronal circuits. Defining the cortical activating areas for spindles by MEG is valuable to consider the underlying neural basis.

A Shout Out to Immature Synapses. Focus on “Different Roles for AMPA and NMDA Receptors in Transmission at the Immature Retinogeniculate Synapse”

A major topic of investigation in the field of developmental neuroscience is to understand how newly formed excitatory synapses receive and transmit information. It is now widely accepted that neural activity plays an important role in a number of developmental processes, including the refinement and establishment of orderly connections (Grubb and Thompson 2004). However, it remains unclear how many immature excitatory synapses (i.e., ones that utilize glutamate as a neurotransmitter) participate in the relay of activity. Contributing to this problem is the finding that immature glutamatergic synapses are comprised largely of N-methyl-D-aspartate (NMDA) receptors and lack AMPA receptors that mediate fast excitatory transmission. Such synapses are said to be “silent,” incapable of causing postsynaptic action potentials from resting levels because in addition to glutamate, the NMDA receptor requires membrane depolarization to relieve a voltage-dependent Mg 2 block. How then do silent synapses “speak” loudly enough to cause postsynaptic firing and thereby successfully relay information? In a recent article, Liu and Chen (2008) provide some answers to this question. They examine the synaptic responses and intrinsic properties of developing neurons by making use of an in vitro thalamic slice preparation that maintains the excitatory synaptic connections between retinal ganglion cells and relay cells of the dorsal lateral geniculate nucleus (LGN). In an elegant series of whole cell recording experiments, they show how a constellation of properties, including ligand-gated channel kinetics, receptor subunit composition, extended presence of neurotransmitter

Cholinergic Modulation of Spindle Bursts in the Neonatal Rat Visual CortexIn Vivo

Acetylcholine (ACh) is known to shape the adult neocortical activity related to behavioral states and processing of sensory information. However, the impact of cholinergic input on the neonatal neuronal activity remains widely unknown. Early during development, the principal activity pattern in the primary visual (V1) cortex is the intermittent self-organized spindle burst oscillation that can be driven by the retinal waves. Here, we assessed the relationship between this early activity pattern and the cholinergic drive by either blocking or augmenting the cholinergic input and investigating the resultant effects on the activity of the rat visual cortex during the first postnatal week in vivo. Blockade of the muscarinic receptors by intracerebroventricular, intracortical, or supracortical atropine application decreased the occurrence of V1 spindle bursts by 50%, both the retina-independent and the optic nerve-mediated spindle bursts being affected. In contrast, blockade of acetylcholine esterase with physostigmine augmented the occurrence, amplitude, and duration of V1 spindle bursts. Whereas direct stimulation of the cholinergic basal forebrain nuclei increased the occurrence probability of V1 spindle bursts, their chronic immunotoxic lesion using 192 IgG-saporin decreased the occurrence of neonatal V1 oscillatory activity by 87%. Thus, the cholinergic input facilitates the neonatal V1 spindle bursts and may prime the developing cortex to operate specifically on relevant early (retinal waves) and later (visual input) stimuli.

Retinal Waves Trigger Spindle Bursts in the Neonatal Rat Visual Cortex

During visual system development, the light-insensitive retina spontaneously generates waves of activity, which are transmitted to the lateral geniculate nucleus. The crucial question is whether retinal waves are further transmitted to the cortex and influence the early cortical patterns of activity. Using simultaneous recordings from the rat retina and visual cortex during the first postnatal week in vivo, we found that spontaneous retinal bursts are correlated with spindle bursts (intermittent network bursts associated with spindle-shape field oscillations) in the contralateral visual cortex (V1). V1 spindle bursts could be evoked by electrical stimulation of the optic nerve. Intraocular injection of forskolin, which augments retinal waves, increased the occurrence of V1 spindle bursts. Blocking propagation of retinal activity, or removal of the retina reduced the frequency, but did not completely eliminate the cortical spindle bursts. These results indicate that spontaneous retinal waves are transmitted to the visual cortex and trigger endogenous spindle bursts. We propose that the interaction between retinal waves and spindle bursts contributes to the development of visual pathways to the cortex.

Early motor activity drives spindle bursts in the developing somatosensory cortex

Sensorimotor coordination emerges early in development. The maturation period is characterized by the establishment of somatotopic cortical maps, the emergence of long-range cortical connections, heightened experience-dependent plasticity and spontaneous uncoordinated skeletal movement. How these various processes cooperate to allow the somatosensory system to form a three-dimensional representation of the body is not known. In the visual system, interactions between spontaneous network patterns and afferent activity have been suggested to be vital for normal development. Although several intrinsic cortical patterns of correlated neuronal activity have been described in developing somatosensory cortex in vitro, the in vivo patterns in the critical developmental period and the influence of physiological sensory inputs on these patterns remain unknown. We report here that in the intact somatosensory cortex of the newborn rat in vivo, spatially confined spindle bursts represent the first and only organized network pattern. The localized spindles are selectively triggered in a somatotopic manner by spontaneous muscle twitches, motor patterns analogous to human fetal movements. We suggest that the interaction between movement-triggered sensory feedback signals and self-organized spindle oscillations shapes the formation of cortical connections required for sensorimotor coordination.

A general automatic method for the analysis of NREM sleep microstructure

Objective To define a unified method for the automatic recognition and quantitative description of EEG phasic events of sleep microstructure occurring during NREM sleep, particularly arousals, phase A subtypes of cyclic alternating pattern and spindles. Methods The NREM sleep EEG of 10 normal young subjects was examined in order to recognize formal phasic events of sleep microstructure. The following ‘formal’ events (i.e. events defined exclusively on the basis of automatic analysis criteria) were classified: arousals, A1-phases (A-phases not including arousals) and A2- and A3-phases (A-phases including arousals). Spindle bursts, corresponding to visually recognized spindles, were also formally defined. The identification of these events was carried out following a three-step procedure: (1) computation of band-related descriptors derived from the EEG signal, (2) introduction of suitable thresholds and (3) application of simple logical principles, i.e. an exclusion principle and an overlapping principle. Results Formal A-phases, arousals and spindle bursts showed spectral characteristics which were consistent with visual inspection. The value of the parameter Correctness for the recognition of the A-phases was 83.5%. In particular, the different physiological distribution of the A-phases in Stage 2 preceding slow wave sleep with respect to Stage 2 preceding REM sleep was confirmed. Conclusions The proposed method provides a unified quantitative approach to the study of sleep microstructure. Visually defined events can be reliably identified by means of automatic recognition.

Absence of sleep spindles in human medial and basal temporal lobes.

All-night recordings from subdural electrocorticographic (ECoG) electrodes on the human medial and basal temporal lobes were analysed to examine spindling activities during sleep. Subjects were three males and three females who were candidates for neurosurgical treatments of partial epilepsy. Subdural electrodes were attached to the medial and basal temporal lobe cortices, allowing ECoG and electroencephalogram from the scalp vertex (Cz EEG) to be recorded simultaneously during all night sleep. In one case, subdural electrodes were attached also on the parietal lobe. Fast Fourier transformation (FFT) analyses were performed on the ECoG and Cz EEG signals. No organized sleep spindles or sigma band (12-16 Hz) peaks in FFT power spectra were observed from the medial or basal temporal lobes of the non-epileptogenic hemispheres during non-rapid eye movement (NREM) sleep. In a case with parietal electrodes, organized spindle bursts were observed in parietal signals synchronized with Cz spindles. Although delta band (0.3-3 Hz) power from both the medial and basal temporal lobes fluctuated across each night as expected, sigma activity changed little. However, 14 Hz oscillatory bursts were observed in the medial basal temporal lobe of epileptogenic hemisphere in two cases and bilaterally in one case during not only NREM sleep but rapid eye movement (REM) sleep and wakefulness. From the present study we conclude that sleep spindle activities are absent in the medial and basal temporal lobes. Fourteen Hz oscillatory bursts observed from the medial or basal temporal lobe in some cases were not considered to be sleep spindles since they also appeared during REM sleep and wakefulness. These waveforms could have originated due to epileptic pathology, since they frequently appeared in epileptic regions.

Opposite effects of T- and L-type Ca 2+ channels blockers in generalized absence epilepsy

The role of the T-type Ca 2+ channel blocker, ethosuximide, the L-type Ca 2+ channel blocker, nimodipine and L-type Ca 2+ channel opener, BAY K8644 (1,4 Dihydro-2,6-dimethyl-5-nitro-4-[trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester), was investigated on spike-wave discharges in WAG/Rij rats. This strain is considered as a genetic model for generalized absence epilepsy. A dose-dependent decrease in the number of spike-wave discharges was found after i.c.v. ethosuximide, an increase after i.p. nimodipine and a decrease after i.c.v. BAY K8644. BAY K8644 was also able to antagonise the effects of nimodipine. Preliminary data were obtained with two conotoxins, MVIIC and GVIA, which block P/Q-type and N-type Ca 2+ channels, respectively. Only after i.c.v. administration of ω-conotoxin GVIA were the number and duration of spike-wave discharges reduced, but animals showed knock-out lying. The latter suggests behavioural or toxic effects and that the decrease in spike-wave activity cannot unequivocally be attributed to blockade of N-type Ca 2+ channels. It can be concluded that T- and L-type Ca 2+ channel blockers show opposite effects on spike-wave discharges. Furthermore, these effects are difficult to explain in terms of a model for spindle burst activity in thalamic relay cells proposed by McCormick and Bal [Sleep and arousal: thalamocortical mechanisms. Ann. Rev. Neurosci. 20 (1997) 185].

Magnetoencephalographic characterization of sleep spindles in humans.

Sleep spindles in EEG recordings of adults are most prominent over the central and frontal midline regions. Early magnetoencephalographic recordings agreed with conventional EEG findings. However, more recent small-array magnetoencephalography and quantitative EEG studies suggest that the source areas for spindles are more widespread. We used a whole-head 122-channel biomagnetometer to characterize the sources of sleep spindles in four normal volunteers. Parallel interactive and automated multiple dipole spatiotemporal source modeling was conducted on the data sets of 10 spindles from each subject. Principal component analysis was used to estimate the number of sources in interactive source modeling, and singular value decomposition was used in automated dipole modeling. Spectral analysis of the epochs containing sleep spindles was performed. Principal component analysis and singular value decomposition suggested that all sleep spindles were made up of activity from multiple sources. Similarly, interactive and automated multiple dipole source modeling showed that three or more sources were present in 75% of spindle bursts. The sources for sleep spindles localized to all four cerebral lobes. Parietal and frontal lobes were the areas most frequently involved. Interactive source modeling resulted in more frequent temporal lobe than occipital dipole localizations; automated source modeling showed more frequent occipital than temporal sources. Spindle source localizations varied across subjects and across different spindles within subjects. Our results indicate that individual sleep spindles are generated by multiple cortical sources that are widespread within and across individuals.

EEG spindle bursts from hippocampus

Abstract This paper reports the case of an epileptic patient who underwent memory testing (delayed matching to sample and paired associates) during electrical recording and stimulation from depth electrode arrays placed for lateralization and localization of seizure onset. EEG recordings from the left, but not right, depth electrodes in mid hippocampus (anterior-posterior) showed an unusual pattern of four bursts of high-voltage spindle activity associated with verbal responses required during the recognition phase of delayed matching to sample tasks on 48 of 51 trials. No such pattern of bursts was observed on longer delayed (180 s) visual-verbal paired associate tasks. Spindle bursts occurred in distinct grouping patterns, only when minimal overt verbal response to object recognition was required, but not under other dissociating situations.

Demonstration pf a 3–5s periodicity between the spindle bursts in NREM sleep in man

Demonstration pf a 3–5s periodicity between the spindle bursts in NREM sleep in man

Effects of VA-045, a novel apovincaminic acid derivative, on age-related impairment evidence in electroencephalograph, caudate spindle, a passive avoidance task and cerebral blood flow in rats

1. 1. The ability of VA-045 to improve aged-related impairment on electroencephalograph (EEG), caudate spindle, performance on a passive avoidance task and cerebral blood flow (CBF) were evaluated in rats. 2. ]2. The cortical EEG of the aged rats showed a higher incidence of spontaneous spindle burst (SSB) than seen in young rats. VA-045 decreased the incidence of SSB in aged rats. In contrast, vinpocetine increased the incidence of SSB in aged rats. 3. 3. Electrical stimulation of the striatum in aged rats lead to a higher incidence of neocortical high voltage spindle (CS) than seen in young rats. In young rats, VA-045 had no effect on the CS, whereas an age-related increase in CS was blocked by VA-045, but was enhanced by vinpocetine. 4. 4. There were no differences in the cortical EEG arousal response elicited by stimulation of the reticular formation of the brain stem in rats of all ages. VA-045 and vinpocetine had no effect on the cortical EEG arousal response in both young and aged rats. 5. 5. VA-045, but not vinpocetine, attenuated the age-related decreased step through latency (STL) on a passive avoidance task. VA-045 and vinpocetine did not enhance the acquisition of learning behavior in a passive avoidance task in young rats. 6. 6. VA-045 increased the cerebral blood flow (CBF) in both young and aged rats and the potency in aged rats was greater than that in young rats. Vinpocetine had no effect on CBF in either young or aged rats. 7. 7. The pharmacological effects of VA-045 on age-related neuronal dysfunction are discussed.