A circadian rhythm of hippocampal theta activity in the mouse

Hippocampal theta activity dominates the cortical EEG of the mouse during certain behaviors. We have therefore been able to study the circadian distribution of hippocampal theta activity by means of chronic EEG implantation and computerized EEG state scoring. Observations in six mice indicate consistent and significant circadian patterns of theta-dominated EEG, both during wakefulness (theta-dominated wake, or TDW) and during sleep (REM sleep). The probability of REM rises gradually to a maximum during the sleep period and then falls abruptly at activity onset and then falls gradually. The complementary circadian patterns of REM and TDW suggest that they may be two episodes of each coincide remarkably, as do their circadian distributions. The probability of TDW rises to a very high level at activity onset and then falls gradually. The complementary circadian patterns of REM and TDW suggest that they may be two halves of a single circadian rhythm of theta probability. This concept would be relevant in interpreting the abnormally phase-advanced pattern of REM sleep observed in human depressives.     

Two populations of rhythmically bursting neurons in rat medial septum are revealed by atropine

1. Previous findings, such as the sensitivity of the hippocampal theta rhythm to cholinergic manipulation, support a "pacemaker" role for the cholinergic cells of the medial septal nucleus and the vertical limb of the nucleus of the diagonal band (MSN-NDB). To explore the mechanism(s) of action of systemic antimuscarinic drugs in eliminating the theta rhythm, recordings of hippocampal EEG and rhythmic MSN-NDB neurons that fired in phase with the hippocampal theta rhythm were taken during the administration of atropine in urethane-anesthetized rats. 2. Twenty-two of 33 rhythmic MSN-NDB cells continued to burst at the theta rhythm frequency after administration of a dose of atropine (25 mg/kg iv) that was sufficient to eliminate the theta rhythm (atropine-resistant cells). The remaining 11 cells lost their rhythmic firing pattern over the same time course as the loss of the theta rhythm (atropine-sensitive cells). 3. Both types of rhythmic MSN-NDB cells could be antidromically driven from the fimbria/fornix with similar latencies (range, 0.5-4.0 ms). The extracellularly recorded spike waveforms were not useful in predicting the atropine sensitivity of a given cell. Atropine-resistant cells frequently had higher firing rates than atropine-sensitive cells, but there was sufficient overlap of the two groups to make this a poor predictor of sensitivity. 4. Cooling the fimbria/fornix reversibly eliminated the hippocampal theta rhythm, but had no effect on 21/25 rhythmic MSN-NDB cells tested. This indicates that the atropine-sensitive MSN-NDB cells do not depend on the periodic output from the hippocampus for their rhythmic firing. Recordings from pairs of rhythmic MSN-NDB cells during cooling and/or atropine administration showed unchanged phase relations at the theta rhythm frequency. In rats in which the septohippocampal system was exposed by aspirating the overlying brain tissue, direct application of atropine (10 mg/ml) to the septal nuclei reversibly eliminated the hippocampal theta rhythm. 5. The rhythmic cells of the MSN-NDB are apparently composed of at least two distinct types, both of which potentially contribute to the production of the theta rhythm in the hippocampus. Elimination of hippocampal theta rhythm after local septal atropine application suggests that the loss of rhythmic activity in the group of atropine-sensitive septal cells is sufficient for the elimination of the theta rhythm. A model of the septohippocampal connections necessary for the theta rhythm is presented.     

The role of hippocampal theta activity in sensory gating in the rat.

Sensory gating is defined as a decreased reaction on the second click, measured as evoked potentials (EP) within a double click paradigm. Recently, it was established that gating in rats was decreased during REM sleep compared to wakefulness and non-REM sleep. REM sleep in the rat is characterized by hippocampal theta rhythm. Therefore, it was investigated whether sensory gating would also be diminished during other states with hippocampal theta. Twelve Wistar rats were implanted with hippocampal electrodes and exposed to double clicks during passive wakefulness, REM sleep, and activity (voluntary movements and walking on a moving belt). Gating was examined by use of the amplitudes of the EPs in reaction to the first conditioned amplitude (CAMP) and second click test amplitude (TAMP), as well as two gating parameters (C-T score and T/C ratio). Except passive wakefulness all behavioral conditions were accompanied by hippocampal theta. Normal gating was always found, except during REM sleep. The CAMP was than lower than during passive wakefulness. Gating was less disturbed during behavioral activity. Negative correlations were found between the percentage theta power on the one side and the CAMP, respectively, the C-T score, on the other. The correlation between the percentage theta power and the T/C ratio was also significant. It is concluded that the presence of hippocampal theta is not a sufficient condition to cause disturbances in auditory sensory gating. Behavioral states that accompany theta activity, however, tend to affect the CAMP. The decrease in gating found during REM sleep cannot be easily related to well-known neurochemical and pharmacological data.     

Neuronal sources of theta rhythm in the entorhinal cortex of the rat

The discharge patterns and layer distribution of entorhinal cortex (EC) units were investigated in paralysed and locally anesthetized rats injected with physostigmine in order to induce theta (theta) rhythm. Entorhinal unit activity and field potentials were recorded simultaneously with the same micropipette. Hippocampal CA1 theta rhythm was used as reference. Statistical analysis included auto- and cross-correlations and interval histograms. Results showed: a. the existence of rhythmic and non-rhythmic cells, both tending to fire in a constant phase relationship with theta rhythm; b. in all EC subdivisions, most rhythmic cells were located in superficial cell layers (II-III); c. on the average, rhythmic cells from the medial EC fired synchronously; d. non-rhythmic cells tended also to fire synchronously but with an opposite phase relationship with respect to rhythmic neurons. Although a complex organization in the rhythmicity of EC units is revealed, it is concluded that the neuronal sources of theta activity in the EC are located in superficial cell layers, and it is strongly suggested that the EC output through the perforant path may rhythmically modulate the discharge pattern of hippocampal pyramidal and dentate granule cells.     

不同行为状态下大鼠脑电时频变化特性的直方图分析

结合应用多分辨率小波分解方法和直方图参数统计方法 ,分析大鼠脑电信号 (Electroencephalogram,EEG)在不同行为状态下的非稳态时频动态变化特性。利用埋植电极记录自由活动大鼠在清醒期、慢波睡眠期和快动眼睡眠期的皮层 EEG,应用小波变换将 EEG分解成 δ、θ、α和 β四个分量 ,求各分量功率对数值直方图和功率百分比值直方图的均值、方差、偏斜度和峭度。结果表明 :EEG功率对数值的分布比较接近正态分布 ,而多数功率百分比值的分布与正态分布差别显著。单因素方差分析结果显示这些直方图统计参数在不同行为状态之间和不同分解分量之间具有显著差别。 EEG在不同时期的某些特征波 (例如 :慢波睡眠期的 δ波、清醒期和快动眼睡眠期的 θ波等 )使功率对数值分布具有较大的偏斜度值和峭度值。由此可见 ,EEG小波分解分量的直方图参数是一种新的描述EEG动态时频变化特性的定量分析指标     

Experimental dissociation between wakefulness and paradoxical sleep hippocampal theta.

The effects of electrolytic lesions of the septum on the theta activity of the dorsal hippocampus were studied in the chronically implanted rat during both wakefulness and paradoxical sleep. The experimental results show that depending on their localization, septal lesions can either: (1) eliminate the wakefulness theta rhythm without suppressing that of paraoxical sleep; (2) eliminate the paradoxical sleep theta rhythm without suppressing that of wakefulness. These results suggest that there are two kinds of theta activity having different anatomophysiological bases and a different functional significance: one associated with wakefulness and the other, with paradoxical sleep.     

Arousal-dependent properties of medial septal neurons in the unanesthetized rat.

We have performed a qualitative and quantitative analysis of the electrophysiological properties of medial septal neurons in the unanesthetized rat. The rat's head was held in a stereotaxic apparatus by a painless head-restrained system that was implanted seven days prior to the recording sessions. Extracellular recordings were made in a mixed population of antidromically identified septohippocampal neurons and unidentified medial septal neurons in different states of arousal and in response to peripheral and reticular stimulations. The spontaneous activity as well as the percentage of rhythmically bursting septal neurons varied significantly according to the state of arousal. Higher values were noted in paradoxical sleep (28 imp/s and 94% of bursting neurons) as compared with wakefulness with hippocampal theta rhythm (17.4 imp/s and 64.2% of bursting neurons) and slow wave sleep (12.3 imp/s and 8% of bursting neurons). The frequency of the bursts was significantly higher during paradoxical sleep. In individual medial septal neurons, arousing stimuli and paradoxical sleep could induce rhythmic bursting activity in previously non-bursting neurons provided that they were fast-firing neurons. No differences were noted in the functional characteristics of neurons in the medial septal nucleus as compared with the diagonal band of Broca. When the unanesthetized rats were compared with a group of urethane-anesthetized rats, the spontaneous activity was higher and more irregular in the absence of anesthesia. The percentage of the bursting neurons was significantly lower in the unanesthetized rats (32.3% vs 43.3%). However, the frequency of the bursts was higher (5.9 +/- 0.1 Hz vs 3.5 +/- 0.1 Hz). Since the patterns of activity of medial septal neurons fluctuate in different physiologically relevant states, previous classifications of these neurons made by ourselves and other authors, in urethane-anesthetized rats, may not be appropriate.     

Repeated blockade of GABAA receptors in the medial septal region induces epileptiform activity in the hippocampus

Changes in the activity of putative interneurons of the stratum oriens of the hippocampus and hippocampal EEG after the delivery of the GABAA receptor antagonist bicuculline (1.0nmol/1microl) to the medial septal region were investigated in awake rabbits. The injection of bicuculline produced a sharp increase in the firing rate in 94.3% of hippocampal cells. The effect of bicuculline on the neuronal theta rhythmicity depended on the number of injections. The first five daily infusions decreased the theta activity in 85.7% of cells. On the fourth to fifth experimental days paroxysmal discharges and 8-15Hz oscillations were recorded in the hippocampal EEG. Six to seven further daily bicuculline injections following a brief diminution of theta activity produced a sharp augmentation of theta oscillations in 78.9% of cells and provoked seizures. Immediately before seizures, stabilization of theta bursts and an increase in burst frequency was usually observed in putative interneurons. During seizures, neuronal rhythmic activity was either disordered and then turned into seizure discharges or was inhibited, partially or completely. In the hippocampal EEG, the power of theta rhythm before seizures usually strongly increased compared with controls. Injection of the GABAA agonist muscimol (30nmol/1microl) 15min before bicuculline infusion prevented the development of seizures. These findings suggest that the interplay between septal neurons via GABAA receptors is critical in the tuning of septal output signals that insure generation of natural theta rhythm as well as adequate functioning of the hippocampus.     

Firing relations of lateral septal neurons to the hippocampal theta rhythm in urethane anesthetized rats

Summary The firing of lateral septal neurons was examined in relation to the hippocampal theta rhythm in urethane anesthetized rats. In general, the firing rates of these cells were low during both theta and non-theta EEG states. There was no significant change in firing rate between the two states (theta: 8.5±9.9 spks/sec; non-theta: 6.0±5.3). Sixty-four of 68 cells fired simple spikes and 4 cells were found to fire bursts of action potentials (complex-spikes). Approximately 30% (21/65) of the cells showed a significant phase relation to the hippocampal theta rhythm. The preferred phases of firing of these 21 cells were broadly distributed. The possibility that the phase-locked firing of LSN cells is due to the phase-locked firing of hippocampal projection cells is discussed.     

Baseline sleep-wake patterns in the pointer dog.

The 24-hr electrographic patterns (EEG, EOG, EMG) of six normal pointer dogs were recorded in a laboratory setting. Two states of sleep (slow-wave and rapid eye movement) and wakefulness (alert and drowsy) were identified. The total recording period comprised 44% of alert wakefulness, 21% of the drowsy state, while slow-wave sleep occupied 23% and REM sleep 12% of the time. The mean length of a REM sleep episode averaged 6 min and the mean REM sleep cycle was 20 min. The mean polycyclic sleep-wake cycle was 83 min. Sleep episodes averaged 45 min and the mean waking episode was 38 min. There was an average of two REM sleep episodes per sleep-wake cycle. The dog has a propensity to sleep over a 16-hr interval from 1300 to 0500 but the most sleep occurred between 2100 and 0400 hr during darkness.     

Periodic behavioral changes during hippocampal theta rhythm elicited by septal stimulation in rats

The influence of an electrical stimulation of the medial septum on the electroencephologram of the dorsal hippocampus and behavior was studied in freely moving rats. A short stimulation at 4–12 Hz frequency always induced orienting behavior (searching, rearing, sniffing, exploration) as soon as hippocampal rhythmic slow activity, or theta rhythm is elicited. An increase in stimulation intensity or in pulse duration led to an increased occurrence of theta rhythm and likewise, to an increase of orienting behavior. Both the theta rhythm and orienting behavior were dependent on the stimulation frequency.During long-lasting septal stimulation at 7 Hz, which elicited a continuous hippocampal theta rhythm, periodic behavioral changes were observed, consisting of orienting behavior alternating with grooming behavior (cleaning, washing, licking, scratching). These rhythmic periods lasted for 3–5 min.The significance of the rhythmic behavioral changes are discussed in relation to the activity of the cholinergic septohippocampal system and to rapid-eye-movement sleep and memory consolidation.     

Phase coupling between rhythmic slow activity and gamma characterizes mesiotemporal rapid-eye-movement sleep in humans

In the human sleep literature there is much controversy regarding the existence and the characteristics of hippocampal rhythmic slow activity (RSA). Generally the human RSA is believed to occur in short bursts of theta activity. An earlier study, however, reported mesiotemporal RSA during rapid-eye-movement (REM) sleep that instead of theta fell in the delta frequency band. We conjectured that if this RSA activity is indeed a human analogue of the animal hippocampal theta then characteristics associated with the animal theta should also be reflected in the human recordings. Here our aim was to examine possible phase coupling between mesiotemporal RSA and gamma activity during REM sleep. The study relied on nine epilepsy surgery candidates implanted with foramen ovale electrodes. Positive half-waves of the 1.5–3 Hz RSA were identified by an automatic algorithm during REM sleep. High-frequency activity was assessed for 11 consecutive 20 Hz–wide frequency bands between 20 and 240 Hz. Increase in high frequency activity was phase coupled with RSA in most frequency bands and patients. Such a phase coupling closely resembles that seen between theta and gamma in rodents. We consider this commonality to be an additional reason for regarding delta rather than theta as the human analogue of RSA in animals.     

Brainstem sites for the carbachol elicitation of the hippocampal theta rhythm in the rat

The effects of brainstem microinjections of carbachol on the hippocampal theta rhythm were examined in urethane anesthetized rats. The two most effective theta-eliciting sites with carbachol were the nucleus pontis oralis (RPO) and the acetylcholine-containing pedunculopontine tegmental nucleus (PPT) of the dorsolateral pontine tegmentum. RPO injections generated theta at mean latencies of 38.5±70.8 s and for mean durations of 12.9±5.1 min. Five of seven RPO injections gave rise to theta virtually instantaneously, i.e., before the completion of the injection. PPT injections generated theta at mean latencies of 1.7±1.1 min and for mean durations of 11.9±6.0 min. Injections rostral or caudal to RPO in the caudal midbrain reticular formation (RF) or the caudal pontine RF (nucleus pontis caudalis) generated theta at considerably longer latencies (generally greater than 5 min) or were without effect. Medullary RF injections essentially failed to alter the hippocampal EEG. The finding that theta was produced at very short latencies at RPO suggests that RPO, the putative brainstem source for the generation of theta, is modulated by a cholinergic input. The further demonstration that theta was also very effectively elicited with PPT injections suggests this acetylcholine-containing nucleus of the dorsolateral pons may be a primary source of cholinergic input to RPO in the generation of theta. The hippocampal theta rhythm is a major event of REM sleep. The present results are consistent with earlier work showing that each of the other major events of REM sleep, as well as the REM state, are cholinergically activated at the level of the pontine tegmentum.     

High-amplitude theta wave bursts during REM sleep and cataplexy in hypocretin-deficient narcoleptic mice

Neurons that release hypocretin (HCRT; orexin) peptides control wake–sleep states and autonomic functions, and are lost in patients with narcolepsy with cataplexy. Bursts of high‐amplitude electroencephalographic (EEG) activity have been reported during behavioural arrests and rapid eye movement sleep (REMS) episodes at sleep onset in HCRT‐deficient narcoleptic mice. Quantitative information on these EEG phenomena is lacking. We aimed to quantify EEG frequency, occurrence rate, daily rhythm and cardiovascular correlates of high‐amplitude EEG bursts during REMS and cataplexy. Twenty HCRT‐deficient mice and 15 congenic wild‐type controls were instrumented with electrodes for sleep recordings and a telemetric blood pressure transducer. Short (1–2 s) high‐amplitude bursts of pointed theta waves (7 Hz) occurred during either REMS or cataplexy in 80% of HCRT‐deficient mice without any significant accompanying modification in systolic blood pressure or heart period. Theta bursts were significantly more likely to occur during the dark period and in the last third of REMS episodes. Similar EEG events were detected in a significantly lower fraction (27%) of wild‐type mice and with a significantly lower occurrence rate (0.8 versus 5 per hour of REMS). These data demonstrate that occurrence of high‐amplitude theta bursts is facilitated during REMS and cataplexy in narcoleptic mice. Analysis of EEG frequency and daily and intra‐episode patterns of event occurrence do not support interpretation of theta bursts as temporally displaced pre‐REMS spindles. Facilitation of high‐amplitude theta bursts may thus represent a novel neurophysiological abnormality associated with chronic HCRT deficiency.     

Rhythmic theta-like unit activity of the hippocampal formation during acquisition and performance of avoidance behavior in rabbits

Neuronal activity was recorded from the hippocampal formation during instrumental conditioning of avoidance behavior in rabbits. The conditional stimuli (CSs) were pure tones, the unconditional stimulus (UCS) was a constant-current footshock, and the response was locomotion in a rotating wheel apparatus. Prior to conditioning the rabbits received pretraining, involving noncontingent presentations of the CSs and the UCS. The specific focus of this report is on neuronal records which displayed rhythmic bursts of action potentials similar to the theta rhythm of the EEG. Early in training, rhythmic theta-like neuronal bursts occurred throughout the CS-UCS interval on trials manifesting the initialmost behavioral conditioned responses (CRs). Late in training during asymptotic CR performance there was a build-up in the frequency and rhythmicity of neuronal bursts prior to the CR. The maximum frequency of bursting (9–10 Hz) always occurred just prior to the CR. Relatively little theta-like activity occurred in the early portions of the CS-UCS interval, in the late stage of training. During pretraining ample preresponse theta-like activity occurred in some subjects but not in others. However, no subject manifested a systematic build-up in bursting prior to behavioral responses in pretraining.     

EFFECTS OF SOME DRUGS ON ELECTROENCEPHALOGRAPHIC FAST ACTIVITY AND DREAM TIME

The purpose of this study was to test the hypothesis that latency of REM onset is a negative function of drug-induced precentral fast (18 to 26 cps) activity in the EEG. Chlorpromazine increased this activity during sleep and wakefulness and decreased latency of REM sleep, whereas α-chloralose, pentothal, and phenobarbital were associated with a decrease of this activity during sleep, increased slow wave sleep, and increased latency of REM sleep. Phenobarbital and pentothal increased this fast activity during wakefulness and drowsiness, respectively. However, 18 to 26 cps precentral activity was reduced during sleep with α-chloralose and pentothal. A supporting study in cats demonstrates apparent synchrony of fast activity in the limbic system and cortex during wakefulness, and chlorpromazine increases fast activity in the limbic system. It is speculated that chlorpromazine enhances the effect of the limbic system on cortical (primarily precentral) activity. The sedatives are thought to potentiate the spontaneous slow wave sleep pattern.     

State-modulation of cortico-cortical connections underlying normal EEG alpha variants

Normal electroencephalographic (EEG) alpha variants appear during relaxed wakefulness with closed eyes, drowsiness period at sleep onset, and rapid eye movement (REM) sleep in bursts without arousal signals. Previous results revealed that fronto-occipital and fronto-frontal alpha coherences became weaker from wakefulness to drowsiness, and finally to REM sleep. The present work was aimed at determining whether a generalized or a unidirectional deactivation of the long fronto-occipital fasciculi, previously proposed to be involved in the alpha rhythm generation, could explain the above-mentioned results. Polynomial regression analyses, applied to the change of alpha coherence with distance along the antero-posterior axis, suggested that the anterior and posterior local circuits show a similar level of activation in all brain states. Bivariate partial correlation analyses between local alpha coherences revealed that such local circuits maintain a reciprocal dependency during wakefulness, but unidirectional during drowsiness (anterior-to-posterior, A-P) and REM sleep (posterior-to-anterior, P-A). From these findings, both anterior and posterior cortical structures are suggested as being involved in the generation of the three alpha variants. If the implication of a double cortical generation source (anterior and posterior) of alpha variants is assumed, these two generators seem to maintain a mutual inter-dependency during wakefulness, whereas during the transition to human sleep, the anterior areas work quite independently of the posterior regions. Finally, the occipital structures may be the driving force for the REM-alpha bursts generation, since involvement of frontal regions demonstrated a high dependence on the posterior neural circuits in the genesis of this sleep event.     

Effects of the muscarinic agonist pilocarpine on vigilance states and locomotor activity in ring doves

Cholinergic systems play a significant role in regulating a variety of behavioral functions in mammals and birds. The aim of this work is to study the effects of the muscarinic agonist pilocarpine on behavioral states by visual inspection and electroencephalographic recording; also, locomotor activity was continuously recorded by infrared interruption system in ring doves. The current results in birds demonstrated that the muscarinic agonist pilocarpine (1 and 3 mg/kg, i.p.) primarily induced theta activity in addition to promote passive waking, while diminished active waking, the EEG slow wave rhythm and REM sleep in ring doves. The locomotor activity recorded continuously in ring doves diminished after pilocarpine treatment, which was in good agreement with the observed reduction of active waking derived of the EEG study. Altogether, the current results are similar to the effects of pilocarpine previously reported in mammals. In conclusion, hippocampal theta rhythm in birds suggests that this rhythm is an ancestral property of hippocampal function and similar cholinergic mechanisms regulate vigilance states and theta generation in mammals and birds.