Hippocampal interneuron activity in unanesthetized rats: relationship to the sleep-wake cycle

Evoked population spikes and interneuronal discharges were recorded throughout the sleep-wake cycle in hippocampal regions CA1 and dentate gyrus (DG) of ten chronically implanted rats. During quiet wakefulness (QW) and slow-wave-sleep (SWS) (non-theta rhythm states), the primary shock of paired stimuli evoked in CA1 both high amplitude population spikes and multiple interneuron discharges when compared to active wakefulness (AW) and rapid-eye-movement (REM) sleep (theta rhythm states). A second shock was delivered to CA1 afferents 60 ms after the first shock. This second shock evoked a small population spikes during non-theta states, whereas it evoked higher amplitude population spikes in theta states. The second shock also evoked unit interneuron discharges in non-theta states but not in theta states. In the dentate gyrus, identical primary afferent stimulation evoked similar interneuron activity and uniform amplitude population spikes throughout the sleep-wake cycle. In contrast, the secondary shocks evoked a striking potentiation of the field population spike during sleep, SWS and REM sleep compared to AW and OW. Evoked DG interneuron spikes following the second population spike were greater in number during SWS compared to the other stages. Our findings suggest that hippocampal field potentials and interneuron activity recorded in vivo are regionally regulated, have unique state-dependent expression and are strongly influenced by inhibitory feed-forward mechanisms.     

Parallel modifications of spatial memory performances, exploration patterns, and hippocampal theta rhythms in fornix-damaged rats: Reversal of oxotremorine.

Learning scores and degrees of divergence of the exploratory patterns (EP) displayed during the acquisition stage of a radial eight-arm maze task were examined in fornix-damaged and sham-operated rats injected either with oxotremorine (0.1 mg/kg) or saline. Modifications of hippocampal rhythmic slow activity (theta) recorded in each condition were analyzed in CA1 and dentate gyrus. Dorsal fornix sections reduced choice accuracy but also induced the adoption of a weakly divergent EP. Oxotremorine in animals with lesions reinstates both learning scores and degree of divergence of EP at the levels respectively observed in saline sham-operated animals. Oxotremorine in sham-operated Ss did not significantly improve choice accuracy but strongly modified the EP. Preoperatively, theta rhythms indicated a decrease of frequency after oxotremorine administration. Postoperatively, they showed an increase of frequency in animals with lesions that were reinstated at the preoperative level by oxotremorine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Epileptic afterdischarge in the hippocampal-entorhinal system: current source density and unit studies

The contribution of the various hippocampal regions to the maintenance of epileptic activity, induced by stimulation of the perforant path or commissural system, was examined in the awake rat. Combination of multiple-site recordings with silicon probes, current source density analysis and unit recordings allowed for a high spatial resolution of the field events. Following perforant path stimulation, seizures began in the dentate gyrus, followed by events in the CA3-CA1 regions. After commissural stimulation, rhythmic bursts in the CA3-CA1 circuitry preceded the activation of the dentate gyrus. Correlation of events in the different subregions indicated that the sustained rhythmic afterdischarge (2-6 Hz) could not be explained by a cycle-by-cycle excitation of principal cell populations in the hippocampal-entorhinal loop. The primary afterdischarge always terminated in the CA1 region, followed by the dentate gyrus, CA3 region and the entorhinal cortex. The duration and pattern of the hippocampal afterdischarge was essentially unaffected by removal of the entorhinal cortex. The emergence of large population spike bursts coincided with a decreased discharge of interneurons in both CA1 and hilar regions. The majority of hilar interneurons displayed a strong amplitude decrement prior to the onset of population spike phase of the afterdischarge. These findings suggest that (i) afterdischarges can independently arise in the CA3-CA1 and entorhinal dentate gyrus circuitries, (ii) reverberation of excitation in the hippocampal-entorhinal loop is not critical for the maintenance of afterdischarges and (iii) decreased activity of the interneuronal network may release population bursting of principal cells.     

Changes in EEG power density during sleep laboratory adaptation

First- and second-night effects on the electroencephalogram (EEG) were investigated by means of polygraphic sleep recordings and all-night spectral analysis. Eighteen normal subjects were studied for three consecutive nights in a hospital sleep laboratory. Visual sleep scoring showed that there was a first-night effect in normal subjects similar to that reported previously [increased wakefulness; decreased total sleep time, sleep efficiency, and rapid eye movement (REM) sleep]. Spectral analysis of the sleep EEG revealed important changes, most of which occurred in REM sleep. Increased delta, theta, and beta1 power densities accompanied by decreased mean frequency were seen in REM sleep in the second night. On the basis of REM sleep deprivation results previously published, our data suggest that the second night could be affected by partial REM sleep deprivation that occurred in the first night. Delta and theta power density values decreased in the first non-rapid eye movement episode of nights 1 and 2; this could result from increased REM sleep pressure. The overall consistency of spectral data in the first and second night with REM sleep findings derived from visual scoring in the first night lends further support to this hypothesis. The sleep disturbance experienced during the first night in a sleep laboratory may be a useful and valid model of transient insomnia. Therefore, we conclude that data from all nights recorded should be included in assessing a subject's sleep.     

Regulation of the septal pacemaker theta rhythm by the cervical nuclei of the midbrain

Neuronal activity in the medial septal region (the medial nucleus and the diagonal band nucleus, MN-DBN) was recorded along with hippocampal EEG traces in conscious rabbits with stimulatory electrodes implanted in the median cervical nucleus (MCN) and the reticular formation (RF) of the midbrain and pons. In all animals with electrodes in the MCN, the background theta activity frequency was low (4.6 +/- 0.15 Hz) as compared with intact rabbits or those with electrodes implanted only in the RF (5.2 +/- 0.19 Hz, p < 0.5). Stimulation of the MCN with weak low-frequency impulses reduced theta volleys from MN-DBN cells, reducing their frequency and regularity and inducing the appearance or strengthening of low-frequency delta modulation. The number of spikes in a volley decreased, and the duration of inter-volley intervals increased. Stimulation of the MCN led to a gradual decrease in the frequency and amplitude of theta waves, induced irregular delta waves and spindles of 12 Hz in the hippocampal EEG. Stimulation of the RF produced the opposite changes in volley activity in the MN-DBN and hippocampal EEG, with increases in theta and decreases in delta components. These results support a role for the midbrain cervical nuclei as structures limiting the generation of theta activity by the reticular-septal system, but do not support the existence of an MN-DBN-independent high-frequency serotoninergic theta rhythm. It is proposed that the effect of the MCN may be important for suppression and switching of attention.     

Comparison of innate EEG parameters in rat lines selected for ethanol preference

Through bidirectional selective breeding, lines of rats that differ greatly in their voluntary alcohol drinking behavior have been developed--namely, the alcohol-preferring (P) and high-alcohol-drinking (HAD) lines and the alcohol-nonpreferring (NP) and low-alcohol-drinking (LAD) lines. The present experiments were designed to determine if an association exists between ethanol preference and features of the electroencephalogram (EEG) during various sleep-wake behaviors. Of the EEG parameters measured, only theta activity in the hippocampus revealed differences in the lines. However, these differences were not generally associated with ethanol preference. The peak frequency and distribution mean of hippocampal theta activity during REM sleep were significantly higher in NP rats than in P, HAD, and LAD rats. In addition, theta frequency during alert immobility tended to be higher in NP rats than in P, HAD, and LAD rats. A qualitative comparison of these data with published data from unselected rats further suggested that the NP rats are uniquely different with respect to theta frequency.     

Long-term and short-term plasticity in the CA1, CA3, and dentate regions of the rat hippocampal slice

Subregions of the rat hippocampal slice were investigated in relation to (a) the presence of long-term potentiation and (b) responsiveness to low-frequency stimulation. Long-term potentiation was observed in CA1, CA3 and dentate. The effect occasionally lasted up to 6 h, developed gradually, and depended upon repeated low-frequency tetani for maximal effect. To low-frequency monosynaptic stimulation, areas CA3 and CA1 exhibit response facilitation whereas the dentate gyrus exhibits response depression. Reponsiveness in all areas was influenced by stimulus frequency. Recovery was rapid in all areas.     

Parallel augmentation of hippocampal long-term potentiation, theta rhythm, and contextual fear conditioning in water-deprived rats.

The influence of water deprivation on hippocampal long-term potentiation (LTP), theta rhythm, and contextual fear conditioning in 56 adult male rats was examined. In Exp 1, hippocampal EEG activity and perforant path LTP were assessed in pentobarbital-anesthetized rats. Water deprivation did not affect baseline cell excitability or low-frequency synaptic transmission in the dentate gyrus, but it increased the magnitude of perforant path LTP and elevated the proportion of theta rhythm in the EEG. In Exp 2, rats were classically conditioned to fear a novel context through the use of aversive footshocks. Water deprivation facilitated the rate of contextual fear conditioning but did not alter the asymptote of learning. Exp 3 demonstrated that the facilitation of contextual fear conditioning was not due to a change in unconditional shock sensitivity. These results suggest that water deprivation exerts an influence on contextual fear conditioning by modulating hippocampal LTP and theta rhythm and that these processes serve to encode contextual information during learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spectral power and coherence analysis of sleep EEG in AIDS patients: decrease in interhemispheric coherence

Fifteen patients aged between 26 and 55 years with the acquired immunodeficiency syndrome (AIDS) and various cerebral manifestations of the disease underwent an all-night sleep electroencephalogram (EEG) registration. The recordings of 15 age-matched volunteers were examined as controls. Sleep stages were determined visually and the following spectral analysis was based on corresponding artifact-free 40-second periods. The sampling rate was 64 second-1, the spectral resolution was 0.25 Hz and the frequency ranged from 0.25-24 Hz. The power density spectra of eight EEG derivations (left and right frontopolar, frontal, central and occipital; reference montage to the ipsilateral Cb electrodes) and the coherence spectra of interhemispheric (interfrontal, interoccipital) and intrahemispheric (frontooccipital, left and right) channel pairs were computed. The power density of the patients in the 11.5-13-Hz frequency range of nonrapid eye movement (NREM) sleep was considerably lower than that of the controls (p < 0.05 and p < 0.01 at left and right frontal derivations, two-tailed Mann-Whitney U test). The power density of rapid eye movement (REM) sleep showed no consistent differences between the two groups. The interfrontal coherence of the whole frequency range below 12 Hz was markedly lower in the patient group. This applied to NREM sleep and also to REM sleep (p < 0.01 and p < 0.001 for different frequency bands between 1 and 12 Hz in NREM and REM sleep). Possible relations to clinical features are discussed.     

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y- and facilitatory A2A-purinoceptors

Repeated administration of amphetamine-like stimulants to rats results in enhanced behavioral responsiveness to subsequent administration of these drugs. Recent evidence suggests corticosterone may play a role in the development of sensitization perhaps through the down-regulation of glucocorticoid receptor (GR). To test this hypothesis further we examined the effects of five daily injections of amphetamine (AMPH) (2.5 mg/kg) on GR mRNA of adult Sprague-Dawley rats. Two other groups received saline for 4 days and then either saline or AMPH on the fifth day. All animals were killed 24 h after the last treatment and in situ hybridization was performed with an antisense mRNA GR probe. Quantification of hippocampal GR was accomplished by computer analysis of digitized images of CA1 and dentate gyrus. Acute AMPH produced a significant up-regulation of GR mRNA in CA1 and a nonsignificant trend towards up-regulation in the dentate gyrus. Repeated exposure to AMPH resulted in a significant down-regulation in CA1, and a nonsignificant trend towards down-regulation in dentate gyrus. These data support a role for hippocampal GR mRNA in the development of behavioral sensitization.     

Personality traits in the first degree relatives of outpatients with depressive disorders

Exposure to high levels of hydrogen sulphide (H2S) in humans has been associated with a number of respiratory and neurological symptoms. Acute toxicity following exposure to high concentrations is well-documented, however, there is little scientific information concerning the effects of exposure to low concentrations. The effects of low levels of H2S on electroencephalographic (EEG) activity in the hippocampus and neocortex were investigated on the freely moving rat (Sprague-Dawley). Hippocampal electrodes were implanted in the dentate gyrus (DG) and CA1 region. Activity was recorded for 10 min just prior to H2S exposure in the presence of air (pre-exposure). Rats were exposed to H2S (25, 50, 75, or 100 ppm) for 3 h/day; data was collected during the final 10 min of each exposure. The total power of hippocampal theta activity increased in a concentration-dependent manner in both DG and CA1; repeated exposures for 5 consecutive days resulted in a cumulative effect that required 2 weeks for complete recovery. The effects were found to be highly significant at all concentrations within subjects. Neocortical EEG and LIA (Large Amplitude Irregular Activity) were unaffected. The results demonstrate that repeated exposure to low levels of H2S can produce cumulative changes in hippocampal function and suggest selectivity of action of this toxicant.     

Effects of systemic atropine sulfate administration on the frequency content of the cat sensorimotor EEG during sleep and waking.

Sensorimotor electroencephalogram (EEG) frequencies in cats were evaluated with power spectral analysis before and after 3 doses of atropine sulfate. All doses of atropine tested caused enhanced EEG slow waves (0–7 Hz) and spindles (8–25 Hz) during waking immobility, and postdrug frequency profiles during slow-wave sleep and waking immobility were identical. With 0.75 mg/kg atropine, movement (head movement, locomotion) resulted in EEG desynchronization and reduced power in all frequencies less than 24 Hz. After 1.5 or 3.0 mg/kg atropine, power in low frequencies remained elevated during movement, but power in spindle frequencies was significantly reduced compared with other states. During active REM sleep after 1.5 mg/kg atropine, power in spindle frequencies was significantly lower than that during quiet REM sleep. These results indicate that the sensorimotor cortical EEG in cats is under the control of multiple systems. At least 1 of these systems is active during movement, and its actions are resistant to muscarinic receptor blockade. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spectral analysis in cyclic changes of human sleep evaluation

In this study cyclic changes of human sleep structure were examined. For whole-night polysomnograms of 35 healthy volunteers of both sexes, manual hypnograms were created and divided into NREM-REM cycles. EEG signals from C3-A2 derivation were analysed by computer using a Fast Fourier Transform (FFT). For consecutive NREM-REM cycles of individual sleep stages, EEG power density contents for delta, theta, alpha, sigma and beta waves were analysed. For consecutive sleep cycles, a clear decrease in NREM sleep duration, especially slow wave sleep duration, was obtained. In addition, a decrease in power density of delta waves was observed. For consecutive sleep cycles, increases in REM sleep duration and in power density of theta and alpha waves were obtained. In consecutive sleep cycles, high amplitude delta slow waves are replaced by higher frequency and lower amplitude waves. Thus stages of NREM sleep are replaced by stages of REM.     

Time-dependent reversal of dentate LTP by 5 Hz stimulation

Field potential recordings were made from the dentate gyrus of urethane-anaesthetized rats in order to investigate the ability of 5 Hz stimulation to reverse long-term potentiation (LTP) induced by a high frequency tetanus. A 10 min train of 5 Hz was found to reverse LTP in a time-dependent fashion: as the interval between tetanus and 5 Hz was increased, LTP became progressively less susceptible to reversal. If 10 min or 30 min intervened between tetanization and 5 Hz stimulation, LTP was unaffected. These results indicate that dentate LTP in vivo exhibits a similar limited time window of vulnerability to reversal by low frequency stimulation to that previously reported in area CA1 in vitro.     

Sleep and EEG power spectrum effects of the 5-HT1A antagonist NAN-190 alone and in combination with citalopram

The sleep and waking and EEG power spectrum effects of the putative 5-HT1A antagonist NAN-190 (0.5 mg/kg, i.p.) were studied alone and in co-administration with the selective serotonin re-uptake inhibitor citalopram (5.0 mg/kg, i.p.) in the rat. Citalopram, as in a prior dose-response study, reduced REM sleep. In addition, a slight increase in NREM sleep was observed. Citalopram reduced NREM fronto-parietal (FP) EEG power density in the 5-20 Hz range. When administered alone, NAN-190 suppressed REM sleep in the first 2 h, and reduced SWS-2 in the first 4 after administration. NAN-190 also suppressed selectively NREM sleep slow-wave activity in both fronto-frontal (FF) and FP EEG power spectrum. When administered in combination with citalopram, an attenuation of the power density reduction in the 7-15 Hz range in the FF EEG of citalopram alone, was observed. However, the EEG power spectral density and REM sleep suppressive effects of NAN-190 were both augmented. The results are compatible with the notion that serotonin is involved in the modulation of the slow wave activity in the EEG during NREM sleep. The results are cordant with other data suggesting that postsynaptic 5-HT1A stimulation might increase slow wave activity in the NREM EEG, and that serotonergic stimulation of other receptor subtypes (possibly 5-HT2) may decrease slow wave activity in the NREM EEG.     

The Role of Hippocampal Regions CA3 and CA1 in Matching Entorhinal Input With Retrieval of Associations Between Objects and Context: Theoretical Comment on Lee et al. (2005).

Models of hippocampal function have proposed different functions for hippocampal regions CA3 and CA1, commonly proposing that CA1 performs a match-mismatch comparison of memory retrieval with sensory input. The study by I. Lee, M. R. Hunsaker, and R. P. Kesner (2005) tested these models using selective lesions of hippocampal subregions (see record 2005-01705-014). Their data suggest that CA3 and the dentate gyrus play an important role in the process of detecting the mismatch when a familiar object is placed in a new spatial location. Lesions of the dentate gyrus and CA3 strongly reduce the enhanced exploration associated with displaced objects, beyond the reduction caused by CA1 lesions. This supports the importance of convergent input to CA3 as well as CA1. Along with recent electrophysiological data, this provides a framework for more specifically modeling the role of CA3 and CA1 in matching sensory input with context-dependent retrieval for memory-guided behavior in different tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrical activity of the hippocampus and cortex in dogs operantly trained to move and to hold still.

Operantly reinforced 6 mongrel dogs in a conditioned avoidance procedure to pedal press during 1 discriminative stimulus and to hold still during another. More dorsal hippocampal theta wave activity, longer series of theta waves, and a higher modal frequency in the theta wave range occurred during pedal pressing than during holding still. These differences transferred from the normal to the paralyzed (Gallamine) state. The occurrence of dorsal hippocampal theta waves was not correlated with desynchronization in the postcrucial gyrus or the posterior portion of the lateral gyrus of the cortex. (31 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of cutaneous and deep pain on the electroencephalogram during sleep--an experimental study

The interaction between sleep and pain has been insufficiently studied, and no experiments have investigated whether pathologic sleep patterns as seen in pain patients can be replicated experimentally by well-defined pain stimuli. An experimental model would therefore be valuable for further studies on the interaction between pain and sleep. In this study, three well-defined experimental stimuli (muscle, joint, and cutaneous pain) were applied during sleep, and the electroencephalogram (EEG) pattern was quantified. The pain stimuli were applied during slow-wave sleep in 10 healthy subjects. Using nine surface recordings, the EEG was sampled before and during pain stimuli. Frequency analysis was performed, resulting in 10 EEG features describing the responses to pain. During the muscle-pain stimulus an arousal effect was observed and a decrease in delta (0.5-3.5 Hz) and sigma (12-14 Hz) as well as increases in alpha 1 (8-10 Hz) and beta (14.5-25 Hz) activities were seen. During joint pain, however, more universal EEG changes were seen with a decrease in the lowest frequency bands [delta, theta (3.5-8 Hz) and alpha 1] and an increase in the higher frequencies [alpha 2 (10-12 Hz), sigma and beta bands]. No background EEG changes were observed during the cutaneous stimulus. There were several differences in the responses from the nine EEG channels, but no derivation seemed especially sensitive to detect the evoked changes. The study highlights the complexity of pain on the sleep EEG. The experimental model has shown that pain from different body structures, as well as signals from various EEG derivations, may give different responses in sleep microstructure.     

Frontal midline theta rhythm and mental activity

Theta rhythm at the midline of the frontal area can be observed in normal subjects, during mental task performance, rest and sleep. Frontal midline theta rhythm (Fm theta) is a train of rhythmic waves at the frequency of 6- Hz and can be induced by various mental tasks. Fm theta is induced not only during mental tasks but also during nocturnal sleep in which it was most frequent during rapid eye movement (REM) and second most frequent during stage 1 of non-REM (NREM) sleep, and the relationship of Fm theta to dream images during sleep was found. It is concluded, therefore, that the appearance of Fm theta is related to mental activity even during sleep. Fm theta shows individual differences and is related to certain personality traits. High Fm theta groups showed the lowest anxiety score in the Manifest Anxiety Scale (MAS), the highest score in the extrovertive scale of the Maudsley Personality Inventory (MPI) and the lowest score in the neurotic scale of MPI. Low Fm theta groups showed the opposite correlation. Significant negative correlation was found between the amount of Fm theta and platelet monoamine oxidase (MAO) activity. Summarizing the above-mentioned results, it may be concluded that the appearance of Fm 0 is related to mental activity, personality traits and platelet MAO activity. Furthermore, the correlation of such markers as platelet MAO activity and Fm theta with personality traits as measured by various psychological tests may prove to be of great importance in the exploration of the biological bases of personality.     

Spectral characteristics of sleep EEG in chronic insomnia

To determine whether the spectral characteristics of the sleep electroencephalogram (EEG) of insomniacs differ from that of healthy subjects, we compared in each of the first four non-rapid eye movement (NREM) and rapid eye movement (REM) episodes: (a) the time courses of absolute power, averaged over the subjects in each group, for the delta, theta, alpha, sigma and beta frequency bands; (b) the relationship between these time courses; and (c) the overnight trend of integrated power in each frequency band. The results show that NREM power, for all frequencies below the beta range, has slower rise rates and reaches lower levels in the insomniac group, whereas beta power is significantly increased. In REM, insomniacs show lower levels in the delta and theta bands, whereas power in the faster frequency bands is significantly increased. Thus, the pathophysiology of insomnia is characterized not only by the generally acknowledged slow wave deficiency, but also by an excessive hyperarousal of the central nervous system throughout the night, affecting both REM and NREM sleep. This hyperarousal is interpreted in terms of the neuronal group theory of sleep which provides a possible explanation for the discrepancies observed between subjective impressions and objective measures of sleep. Also, it is suggested that the progressive hyperpolarization of the thalamocortical neurons as sleep deepens is slower in the patient population and that this may explain the observed slow wave deficiency. The homeostatic control of slow wave activity, on the other hand, would appear to be intact in the patient population.