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Synaptic plasticity in the hippocampus during afferent activation reproducing the pattern of the theta rhythm (theta plasticity).

This review summarizes data on the plasticity of hippocampal synaptic pathways in conditions of afferent activation modeling the electrical activity of neurons during the theta rhythm. Activation with short trains of stimuli with frequencies of about 5 Hz efficiently induces long-term potentiation, i.e., stable facilitation of synaptic transmission. Contrarily, single stimuli presented at the same frequency "depotentiate" synapses or even induce long-term depression. Combined theta activity at two synaptic inputs, in phase with each other, induces long-term potentiation, while combined activity in antiphase produces long-term depression of the weakly-activated input (associative long-term potentiation and depression). Short trains of single stimuli at a frequency of 5 Hz induce heterosynaptic short-term depression: the efficiency of all synaptic inputs is decreased for time periods of the order of 1 min. Apart from changes in synaptic efficiency, theta activation affects the ability to induce synaptic rearrangements in conditions of subsequent afferent activation ("cryptic" plasticity). Thus, virtually all known types of synaptic plasticity are efficiently induced by afferent activation of the pattern of the hippocampal theta rhythm, which suggests the possible mechanisms for its roles in learning and memory processes.

Animals↗

Phase precession of medial prefrontal cortical activity relative to the hippocampal theta rhythm.

Theta phase-locking and phase precession are two related phenomena reflecting coordination of hippocampal place cell firing with the local, ongoing theta rhythm. The mechanisms and functions of both the phenomena remain unclear, though the robust correlation between firing phase and location of the animal has lead to the suggestion that this phase relationship constitutes a temporal code for spatial information. Recent work has described theta phase-locking in the rat medial prefrontal cortex (mPFC), a structure with direct anatomical and functional links to the hippocampus. Here, we describe an initial characterization of phase precession in the mPFC relative to the CA1 theta rhythm. mPFC phase precession was most robust during behavioral epochs known to be associated with enhanced theta-frequency coordination of CA1 and mPFC activities. Precession was coherent across the mPFC population, with multiple neurons precessing in parallel as a function of location of the animal. The existence of phase precession beyond the hippocampus implies a more global role for this phenomenon during theta rhythm-mediated coordination of neural activity.

Action Potentials↗

[Synaptic plasticity in the hippocampus during afferent activation reproducing a theta-rhythm pattern (theta plasticity)].

The data are reviewed concerning synaptic plasticity of the hippocampal monosynaptic pathways evoked by afferent activation which simulates activity of neurons in theta-rhythm. Activation with short high-frequency bursts applied with 5 Hz frequency effectively induces long-term potentiation. In contrast, activation with single pulses at 5 Hz causes the depotentiation or even long-term depression of the activated synapses. "In-phase" activation of two afferent pathways in the theta-rhythm induces long-term potentiation, while the "out-of-phase" activation induces long-term depression of a "weak"" pathway. A train of 30-50 pulses at 5 Hz evokes heterosynaptic short-term depression, i.e., a suppression of all synaptic inputs for 1 min. So-called "hidden" plasticity (the enhancement of the effect of delayed activation in producing long-term depression) is also effectively evoked by the theta-like activatory patterns. Therefore, practically all known types of synaptic plasticity can be effectively evoked by the afferent activation which reproduce the pattern of the hippocampal theta-rhythm. These phenomena can underlie the theta-rhythm participation in learning and memory.

Afferent Pathways↗

Frontal midline theta rhythm: differentiating the physiological theta rhythm from the abnormal discharge.

The theta rhythm that appears in the frontal midline was studied morphologically and clinically in EEGs performed on 788 patients and 161 normal subjects in their late teens or older. This theta rhythm was classified into 2 types. The Type 1 theta rhythm appeared in short bursts maximally in the Fz lead and spread mainly to the anterior region. It had a high frequency, low voltage and regular waveform. The Type 2 theta rhythm appeared in long runs maximally in the Fz lead and spread mainly to the posterior areas. It had a relatively low frequency, high voltage and irregular waveform. Type 1 was observed in a younger age group (mean age: 20.3 years) that was comprised of healthy subjects and one mentally retarded patient. In no case was the Type 1 theta rhythm accompanied by a paroxysmal EEG abnormality. We therefore believe that Type 1 is a physiological EEG activity (Fm theta). On the other hand, Type 2 was observed in a relatively older age group (mean age: 30.7 years) comprised of patients diagnosed as having epilepsy or intractable headaches. Five of 9 cases showed epileptic EEG abnormalities. We therefore believe that Type 2 might have clinical significance in diagnosis of epilepsy and other cerebral dysfunctions. The EEG pattern that we call the frontal mid-line theta rhythm may be either a physiological theta rhythm or an abnormal discharge. It is possible to determine whether the theta rhythm is the former or the latter, and we believe this differentiation to be clinically important.

Adolescent↗

Involvement of GABAergic and cholinergic medial septal neurons in hippocampal theta rhythm.

Hippocampal theta rhythm (HPCtheta) may be important for various phenomena, including attention and acquisition of sensory information. Two types of HPCtheta (types I and II) exist based on pharmacological, behavioral, and electrophysiological characteristics. Both types occur during locomotion, whereas only type II (atropine-sensitive) is present under urethane anesthesia. The circuit of HPCtheta synchronization includes the medial septum-diagonal band of Broca (MSDB), with cholinergic and gamma-aminobutyric acid (GABA)ergic neurons comprising the two main projections from MSDB to HPC. The primary aim of the present study was to assess the effects of GABAergic MSDB lesions on urethane- and locomotion-related HPCtheta, and compare these effects to those of cholinergic MSDB lesions. Saline, kainic acid (KA), or 192 IgG-saporin (SAP) was injected into MSDB before recording. KA preferentially destroys GABAergic MSDB neurons, whereas SAP selectively eliminates cholinergic MSDB neurons. A fixed recording electrode was placed in the dentate mid-molecular layer, and stimulating electrodes were placed in the posterior hypothalamus (PH), and medial perforant path (PP). Under urethane anesthesia, HPCtheta was induced by tail pinch, PH stimulation, and systemic physostigmine; none of the rats with KA or SAP showed HPCtheta in any of these conditions. During locomotion, HPCtheta was attenuated, but not eliminated, in rats with KA or SAP lesions. Intraseptal KA in combination with either intraseptal SAP or PP lesions reduced locomotion-related HPCtheta beyond that observed with each lesion alone, virtually eliminating HPCtheta. In contrast, intraseptal SAP combined with PP lesions did not reduce HPCtheta beyond the effect of each lesion alone. We conclude that both GABAergic and cholinergic MSDB neurons are necessary for HPCtheta under urethane, and that each of these septohippocampal projections contributes to HPCtheta during locomotion.

Acetylcholine↗

Do septal neurons pace the hippocampal theta rhythm?

The hippocampal theta rhythm (rhythmical slow activity, RSA) is one of the most thoroughly studied EEG phenomena. Much of this experimental interest has been stimulated by suggestions that the mnemonic functions of the hippocampus may depend upon theta-related neuronal activity. Inputs from the medial septal nuclei to the hippocampus were shown to be essential for the theta rhythm in the 1950s, but the role of these basal forebrain projections has not been clearly defined. Four models of the septo-hippocampal connections involved in theta rhythm production are reviewed as the precise roles of these projections are discussed. In our final, consolidated model both cholinergic and GABAergic septal projection cells fire in rhythmic bursts that entrain hippocampal interneurons. The resulting rhythmic inhibition of hippocampal projection cells, together with their excitatory interconnections, generates at least one component of the theta rhythm.

Action Potentials↗

Midline theta rhythm revisited.

The midline theta rhythm consists of runs of theta waves occurring in the midline, especially in the central and parietal vertex regions. Few reports regarding this uncommon EEG finding have been published. It has been given various names, e.g. theta discharges in the middle-line, theta spindles, etc. Out of the 4,236 patients who were administered EEG examinations during an investigation period of 9 months, the midline theta rhythm, with a frequency in the range of 4-7 Hz, voltage over 50 microV, duration over 3 seconds, and most prominent in the central and parietal vertex areas, was recorded in 35 (0.83%). The age distribution of these patients peaked in two groups, adults aged 21-40 years and elderly patients aged 61-77 years. The waveform of the theta rhythm observed in adults 40 years old and under was often sinusoidal and regular. In this group, the most common clinical disorder was epilepsy. Often, the appearance of the theta rhythm observed in elderly patients was triangular and irregular, and sometimes sharp. In this group, the common clinical symptoms were headaches and dizziness, characterized by diagnoses of organic brain diseases such as cerebrovascular disorders. This study re-examines the clinical significance of the midline theta rhythm, taking into consideration studies that have been published in the past.

Adult↗

Nucleus incertus contribution to hippocampal theta rhythm generation.

The hippocampal theta rhythm is generated by the pacemaker activity of the medial septum-diagonal band of Broca (MS/DBB) neurons. These nuclei are influenced by brainstem structures that modulate the theta rhythm. The aim of the present work is to determine whether the nucleus incertus (NI), which has important anatomical connections with the MS/DBB, contributes to the hippocampal theta rhythm generation in rats. Hippocampal field activity was recorded in urethane-anaesthetized rats. Electrical stimulation of the NI not only evoked theta rhythm in the hippocampus, but also decreased the amplitude of delta waves. Unit recordings in the NI revealed either a non-rhythm discharge pattern in most neurons (76%), or a rhythm activity at 13-25 Hz in the remaining neurons. The firing rate of these neurons increased during the presence of theta rhythm evoked by either sensory or reticularis pontis oralis nucleus (RPO) stimulation. Electrolytic lesions of NI, or the microinjection of the gamma-aminobutyric acid (GABA)A agonist muscimol, abolished the theta rhythm evoked by RPO stimulation. Consequently, the NI may be a relay station between brainstem structures and the MS/DBB in the control of the hippocampal theta rhythm generation.

Animals↗

Medial prefrontal cortex generates frontal midline theta rhythm.

Frontal midline theta rhythm (Fm theta) is a distinct theta activity of EEG in the frontal midline area that appears during concentrated performance of mental tasks in normal subjects and reflects focused attentional processing. To tomographically visualize the source current density distributions of Fm theta, we recorded Fm theta by using a 64-channel whole-head MEG system from four healthy subjects, and applied a new analysis method, synthetic aperture magnetometry (SAM), an adaptive beam forming method. Fm theta was observed in the MEG signals over the bilateral frontal regions. SAM analysis showed bilateral medial prefrontal cortices, including anterior cingulate cortex, as the source of Fm theta. This result suggests that focused attention is mainly related to medial prefrontal cortex.

Adult↗

Intrinsic oscillations in CA3 hippocampal pyramids: physiological relevance to theta rhythm generation.

The theta rhythm is the most remarkable hippocampal activity correlated with various physiological and behavioral phenomena. Although analyzed by numerous investigators, during the last five decades, the mechanisms that lead to its generation still remain reason of debate. In the present report it is shown that hippocampal neurons, recorded from juvenile and adult slices, are endowed with intrinsic properties that allow the generation of a steady oscillatory activity. The frequency of this rhythmic ongoing process is highly sensitive to the level of the membrane potential, reaching values in the theta range, up to 6 Hz, for more depolarized values of membrane potential. Membrane potential oscillations are unmasked by loading pyramidal neurons with intracellular cesium, are sodium-independent, and are generated by the sequential activation of calcium and potassium conductances. Finally, like theta rhythm, regularly occurring membrane potential oscillations can be detected since postnatal day 10 and their frequency increases with age, i.e., during the following 2 weeks.

4-Aminopyridine↗

Interactions between hippocampal penicillin spikes and theta rhythm.

The relationships between theta rhythm and epileptic spikes, evoked by penicillin, were studied in the rat hippocampus. Records were taped and processed off-line, and autocorrelation functions, averages and power spectra of the EEG and frequency histograms of the epileptic spikes were calculated. Results showed that: (1) epileptic spikes tend to occur in a preferred phase of theta rhythm; (2) they provoked a reset of the phase of theta rhythm, acting as internal stimuli; (3) epileptic spikes decreased in frequency and were often abolished when theta rhythm was evoked; (4) these effects appeared to be dependent on the medial septal pathway. These findings indicate the existence of an antagonism between two hippocampal phenomena (epilepsy and theta rhythm). On the other hand, they also seem to be interrelated since the generation of one is accompanied by a reciprocal decrease in the other.

Animals↗

Hippocampal theta rhythm synchronizes visual neurons in sleep and waking.

The hippocampal theta rhythm (theta) was reported to be associated with movements, attention, auditory processing, autonomic functions, learning and memory and postulated as an associator of discontiguous events. Since visual information includes temporal cues, our study was centered on the correlation between hippocampal theta rhythm and lateral geniculate activity. Phase relationships between hippocampal theta and unit firing were found with both spontaneous and light evoked activity during wakefulness, slow wave and paradoxical sleep. This temporal correlation was dynamic, exhibiting changes related to the sleep-waking cycle and perhaps to attention shifts. Hippocampal theta rhythm may supply a low frequency temporal dimension to the processing of visual information.

Action Potentials↗

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.

Frontal Lobe↗

Age-related changes in rat hippocampal theta rhythms: a difference between type 1 and type 2 theta.

The age-related changes in two types of theta rhythms recorded from the hippocampus in young (4 months-old), mature (12-13 months-old) and aged (22-25 months-old) rats were investigated. The type 1 theta rhythm was measured from hippocampal EEG recorded from walking rats and the type 2 theta was measured from the EEG induced by reticular pontin oralis nucleus (PON) stimulation in urethane anesthetized rats. The peak frequency and the peak power were detected from power spectra calculated on each theta sample by fast Fourier transformation (FFT). No age-related alteration was observed on the peak frequency of type 1 theta rhythm. However, on type 2 theta rhythm, the peak frequency was decreased in the aged rats compared with the young and the mature rats. The type 2 theta rhythm is cholinergic, and therefore this result suggests that age-related deterioration can be clearly observed in the cholinergic system including the hippocampus in rats.

Aging↗

Hippocampal and entorhinal glucose metabolism in relation to cholinergic theta rhythm.

Hippocampal and entorhinal cortex glucose metabolism were studied by 14C-2-deoxyglucose (2-DG) autoradiography in anesthetized rats with and without continuous theta rhythm (theta). 2-Deoxyglucose changes in specific cytoarchitectonic regions were precisely assessed by n innovative approach. In the absence of theta there were areas with a higher glucose metabolism corresponding to neuropile regions at CA3, dentate gyrus, and subiculum, while the cellular layers always showed lower values. In the presence of theta, provoked by intraventricular injections of anticholinesterases (i.e., physostigmine) or curarimimetics (i.e., d-tubocurarine), 2-DG uptake showed two opposite significant changes in relation to controls: a) it increased in the outer zone of the molecular layer (inner blade) of the dentate gyrus, and in the stratum lacunosum-moleculare of CA3, suggesting an increase in perforant path input during theta rhythm; b) it decreased in the hilar dentate region. This noteworthy decrease in metabolic activity probably reflects an hilar inhibition by local circuits during theta rhythm generation.

Acetylcholine↗

Background activity of rabbit hippocampal neurons in conditions of functional exclusion of structures which regulate the theta rhythm.

The functional importance of theta modulation in the activity of hippocampal neurons was further analyzed using a method consisting of controlled sequential short-term (25-30 min) inclusion or exclusion of the theta rhythm by local administration of lidocaine into the median cervical nucleus and medial septal region respectively. Studies were carried out using conscious rabbits with extracellular recording of hippocampal neuron activity in field CA1. Administration of lidocaine into the medial septal nucleus and diagonal tract nucleus (MS-DT) led to complete inhibition of theta modulation in neuronal and total hippocampus activity. The mean frequency of background discharges underwent no change in most neurons, but decreased significantly in a limited group of cells with high-frequency activity (presumptive inhibitory neurons). Administration of lidocaine into the median cervical nucleus (MCN), the source of serotoninergic pathways to the MS-DT and hippocampus, was accompanied by increases in the stability and frequency of theta modulation of neuronal activity, induction of theta modulation in an additional group of neurons, and expression of a continuous theta rhythm in the electrical activity (EA) of the hippocampus. The mean frequency and regularity of discharges increased in most cells. These data support the existence of tonic inhibitory effects on the part of the MCN on the septa-hippocampal system generating the theta rhythm; in this regard, the MCN can be regarded as an antagonist of the activating reticular formation.

Anesthetics, Local↗

Neuronal sources of theta rhythm in the entorhinal cortex of the rat. I. Laminar distribution of theta field potentials.

The laminar distribution of theta (theta) field potentials in the entorhinal cortex (EC) was investigated in paralysed and locally anesthetized rats injected with physostigmine in order to induce theta rhythm. Electrode penetrations through the medial, intermediate and lateral subdivisions of the EC showed in all cases: 1. the presence of theta rhythm from layer VI to layer III approximately in phase with CA1 theta rhythm; 2. an amplitude minimum between the outer third of layer III and the inner half of layer I; and 3. a phase-reversed theta rhythm in layers II-I with an amplitude maximum in the outer half of layer I. Results indicate the existence of neuronal sources of theta rhythm in the EC.

Action Potentials↗

Neuromagnetic measurement of unilateral temporo-parietal theta rhythm in patients with internal carotid artery occlusive disease.

Rhythmic theta activity detected by electroencephalography (EEG) may be correlated with cerebrovascular brain diseases. Magnetoencephalography (MEG) has higher sensitivity and spatial resolution than conventional scalp EEG, so may be a better method to detect theta rhythm in patients with internal carotid artery (ICA) occlusive disease. Simultaneous EEG and MEG were performed in the awake state in 48 patients with unilateral (n = 42) or bilateral (n = 6) stenotic lesions (more than 60% occlusion) of the ICA (n = 47) or middle cerebral artery (n = 7), and in 27 age-matched healthy normal subjects. No subject had severe neurological deficits. MEG detected the theta rhythm (6-8 Hz) in 14 of 48 patients: ipsilateral to the stenotic or occluded side in 13 hemispheres and bilaterally in one patient with unilateral lesion. The source of the MEG theta rhythm was estimated in the dorsolateral temporo-parietal area, regardless of the location of infarct foci or the stenotic portion of the ICA system. The temporo-parietal theta rhythm was separated from the occipital alpha rhythm by frequency and distribution in MEG. The theta rhythm was found in only two patients by EEG, as well as by MEG. MEG provided better separation of this theta rhythm from the occipital alpha rhythm. Neither MEG nor EEG detected this theta rhythm in the normal subjects. Unilateral temporo-parietal theta rhythm is correlated with the hemisphere with ICA occlusive disease. This rhythm may indicate mild or subclinical abnormalities in the ICA system. MEG is superior to EEG for the detection and localization of theta rhythm.

Adult↗