Biomedical subjects

L W Leung

Publications and source records attributed to L W Leung.

At least 19 recordsLinked to original sources

PubMed1991

Intrinsic membrane potential oscillations in hippocampal neurons in vitro.

Membrane potential oscillations (MPOs) of 2-10 Hz and up to 6 mV were found in almost all stable hippocampal CA1 and CA3 neurons in the in vitro slice preparation. MPOs were prominent for pyramidal cells but less pronounced in putative interneurons. MPOs were activated at threshold depolarizations that evoked a spike and the frequency of the MPOs increased with the level of depolarization. MPOs were distinct from and seemed to regulate spiking, with a spike often riding near the top of a depolarizing MPO wave. Analysis of the periodicity of the oscillations indicate that the period of MPOs did not depend on the afterhyperpolarization (AHP) following a single spike. MPOs persisted in low (0-0.1 mM) Ca2+ medium, with or without Cd2+ (0.2 mM), when synaptic transmission was blocked. Choline-substituted low-Na+ (0-26 mM) medium, 3 microM tetrodotoxin (TTX) or intracellular injection of QX-314 reduced or abolished the fast Na(+)-spike and reduced inward anomalous rectification. About 40% of CA1 neurons had no MPOs after Na+ currents were blocked, suggesting that these MPOs were Na(+)-dependent. In about 60% of the cells, a large depolarization activated Ca(2+)-dependent MPOs and slow spikes. MPOs were not critically affected by extracellular Ba2+ or Cs2+, or by 0.2 mM 4-aminopyridine, with or without 2 mM tetraethylammonium (TEA). However, in 5-10 mM TEA medium, MPOs were mostly replaced by 0.2-3 Hz spontaneous bursts of wide-duration spikes followed by large AHPs. Low Ca2+, Cd2+ medium greatly reduced the spike width but not the spike-bursts. In conclusion, each cycle of an MPO in normal medium probably consists of a depolarization phase mediated by Na+ currents, possibly mixed with Ca2+ currents activated at a higher depolarization. The repolarization/hyperpolarization phase may be mediated by Na+/Ca2+ current inactivation and partly by TEA-sensitive, possibly the delayed rectifier, K+ currents. The presence of prominent intrinsic, low-threshold MPOs in all hippocampal pyramidal neurons suggests that MPOs may play an important role in information processing in the hippocampus.

2-Amino-5-phosphonovalerate↗

PubMed1991

A movement-associated fast rolandic rhythm.

A stereotyped 32 Hz rolandic rhythm maximal over the mesial cortex and occurring only with voluntary movement is described in a patient with tonic postural seizures. This abnormal but nonictal rhythm, which is probably generated subcortically, is expressed synchronously at the level of the cortex and peripherally in the EMG.

Adult↗

PubMed1990

Spontaneous hippocampal interictal spikes following local kindling: time-course of change and relation to behavioral seizures.

Spontaneous interictal spikes (SISs) were recorded in the hippocampus in freely behaving rats following hippocampal stimulations that resulted in afterdischarges (ADs). Hippocampal SISs were detected after an average of 5 (range 2-10) daily ADs. The rate of SISs typically increased minutes after a tetanus, and then decayed with time constants of approximately 70 min and 1.5 days. Seizure onset in the kindling paradigm was not related to a consistent change in SIS rate. Following the interruption of daily kindling, SIS rate invariably decreased to near zero by 4-8 days while seizure susceptibility, as tested by the ability to evoke generalized convulsions, remained unchanged. Despite having a low or zero SIS rate the hippocampus seemed to retain an excitability after kindling interruption, as demonstrated by the observation that an average of 1.7 rekindling stimulations resulted in a high SIS rate. In conclusion, changes in hippocampal SISs were closely time-locked to an AD, and not to evoked behavioral seizures. Hippocampal SISs probably reflect an excitability change that is more local than that necessary for evoking behavioral convulsions. The persistence of SISs in terms of hours and days suggests the involvement of long-term potentiation.

Action Potentials↗

PubMed1989

The role of serotonin in the control of cerebral activity: studies with intracerebral 5,7-dihydroxytryptamine.

Intact rats treated with centrally acting antimuscarinic (atropinic) drugs display large amplitude irregular slow waves in both the neocortex and hippocampus during behavioral immobility and some stereotyped automatic behaviors (Type 2 behavior). However, rhythmical slow activity in the hippocampus and low voltage fast activity in the neocortex occur in close correlation with spontaneous changes in posture, head movement, walking, rearing, swimming or struggling when held (Type 1 behavior). It has previously been proposed that these waveforms, jointly referred to as atropine-resistant cerebral activation (ARCA) are dependent on ascending serotonergic projections. As a further test of this hypothesis, we have studied rats in which forebrain levels of serotonin and 5-hydroxyindoleacetic acid were reduced to 3-10% of control levels as a result of multiple intrabrainstem injections of 5,7-dihydroxytryptamine. This treatment strongly reduced or abolished ARCA in most cases but did not reduce atropine-sensitive cerebral activation which appears to be dependent on ascending cholinergic projections from the basal forebrain to the cerebral cortex. Therefore, ARCA appears to be dependent on ascending serotonergic inputs to the forebrain.

5,7-Dihydroxytryptamine↗

PubMed1988

Hippocampal interictal spikes induced by kindling: relations to behavior and EEG.

Hippocampal spontaneous interictal spikes (SISs) were recorded during the course of daily tetanization (kindling) of afferent fibers to the hippocampal CA1 region. SISs were detected after 3-10 tetanizations. A clear variation of SIS rate with behavior was observed. SIS rate was high during slow-wave sleep (SWS), waking immobility, face-washing and chewing and low during rapid-eye-movement sleep (REMS), walking and rearing. Scopolamine hydrochloride (2.5-5 mg/kg i.p.) increased the SIS rate during walking. Despite the negative correlation of SIS occurrence with the theta rhythm in normal rats, abolishing the theta rhythm by medial septal lesions did not affect the suppression of SISs during REMS as compared to SWS. When interictal or postictal spikes were seen together with the theta rhythm, the spikes tended to occur at a phase of about 240 degrees after the positive peak of the alvear surface rhythm.

Animals↗

PubMed1988

APV, an N-methyl-D-aspartate receptor antagonist, blocks the hippocampal theta rhythm in behaving rats.

2-Aminophosphonovaleric acid (APV), an N-methyl-D-aspartate (NMDA) receptor antagonist, was infused into the lateral ventricles of behaving rats. A 10 or 20 microgram dose of APV attenuated the hippocampal theta rhythm and the theta phase-shift at the apical dendrites of hippocampal CA1 region. A selective suppression of the atropine-sensitive theta rhythm was suggested.

2-Amino-5-phosphonovalerate↗

PubMed1987

Hippocampal electrical activity following local tetanization. I. Afterdischarges.

Following a short (1-10 s) train of repetitive stimulation delivered to the hippocampal CA1 region, the following sequelae of afterdischarges (ADs) was seen: (1) a silent period of 2-4 s, (2) a large primary (1 degree) AD usually alvear-surface negative and deep positive, (3) a period of suppressed hippocampal EEG, (4) a secondary (2 degrees) hippocampal AD, and after 3-6 min, (5) 15-25 min of enhanced (up to 10 times normal) fast (30-70 Hz) waves. The 2 degrees hippocampal AD was preceded by or simultaneous with large AD at the amygdaloid electrodes. Electrolytic lesions (n = 7) or large heat lesions of the amygdala (n = 5) or electrolytic lesions of the medial septum (n = 10) were not successful in suppressing the 2 degrees hippocampal AD. However, 4 rats with radiofrequency lesion and 3 rats with bilateral aspiration lesion of the entorhinal cortex had diminished or no 2 degrees hippocampal AD. The fast waves after tetanization were reversed 180 degrees across surface and deep CA1 electrodes. The fast wave increase was blocked by atropine sulfate (25-50 mg/kg i.p.), scopolamine hydrochloride (5 mg/kg i.p.) and medial septal lesions. It was concluded that the 2 degrees hippocampal AD may depend on a reverberation of neural circuitry involving the entorhinal cortex. The 2 degrees AD recorded from amygdala electrodes may partly reflect spreading of activities from the entorhinal cortex. On the other hand, the increase in fast waves after tetanization requires an intact septohippocampal, muscarinic cholinergic input, and may depend on an enhanced cholinergic input or an increased response.

Action Potentials↗

PubMed1987

Electrical activity of the cingulate cortex. I. Generating mechanisms and relations to behavior.

Spontaneous slow waves (EEG) and multiple unit activity (MUA) were recorded in the posterior cingulate cortex (area 29) and the dorsal hippocampus of the freely moving rat by means of chronically implanted electrodes. Three different wave patterns were discerned in the cingulate EEG. Irregular slow waves occurred during grooming, drinking, eating (Type II behavior) and slow-wave sleep (SWS). The irregular waves also contained sharp transients of about 20 ms duration called EEG-spikes. EEG-spikes reversed their polarity within the cingulate cortex and correlated with an increase in cingulate MUA. They were probably generated by deep (layer IV to VI) neurons in the cingulate cortex. Theta rhythm of 6-10 Hz accompanied walking, rearing, postural shifts, head movements (Type I behavior) and rapid-eye-movement sleep (REMS). MUA of low-amplitude units was phase-locked to the local theta waves, suggesting local generation of the slow waves. However, volume-conduction from the hippocampus would likely contribute to the cingulate theta since no reversal of the theta waves was found in the cingulate cortex. Fast waves of greater than 30 Hz were generally larger during Type I than during Type II behavior. Cellular generators for fast waves are not known. High-amplitude (greater than 100 microV) MUA only appeared during Type II behavior, and in particular during SWS. During REMS, these units were silent. Stimulation of the contralateral homotopic cingulate cortex gave antidromic and synaptic components in the average evoked potential (AEP). The long latency waves of the AEP varied with behaviors and appeared oscillatory (25-40 Hz) during Type I but not during Type II behavior. In summary, the cingulate cortex has a rich gamut of spontaneous and evoked electrical activities which bears some resemblance to that of the hippocampus.

Animals↗

PubMed1987

Electrical activity of the cingulate cortex. II. Cholinergic modulation.

The role of the cholinergic innervation in the modulation of cingulate electrical activity was studied by means of pharmacological manipulations and brain lesions. In the normal rat, an irregular slow activity (ISA) accompanied with EEG-spikes was recorded in the cingulate cortex during immobility as compared to walking. Atropine sulfate, but not atropine methyl nitrate, increased ISA and the frequency of cingulate EEG-spikes. Pilocarpine suppressed ISA and EEG-spikes during immobility, and induced a slow (4-7 Hz) theta rhythm. Unilateral or bilateral lesions of the substantia innominata and ventral globus pallidus area using kainic acid did not significantly change the cingulate EEG or its relation to behavior. Large electrolytic lesions of the medial septal nuclei and vertical limbs of the diagonal band generally decreased or abolished all theta activity in the cingulate cortex and the hippocampus. However, in 5 rats the cingulate theta rhythm increased while the hippocampal theta disappeared after a medial septal lesion. The large, postlesion cingulate theta, accompanied by sharp EEG-spikes during its negative phase, is an unequivocal demonstration of the existence of a theta rhythm in the cingulate cortex, independent of the hippocampal rhythm. Cholinergic afferents from the medial septum and diagonal band nuclei are inferred to be responsible for the behavioral suppression of cingulate EEG-spikes and ISA, and partially for the generation of a local cingulate theta rhythm. However, an atropine-resistant pathway and a theta-suppressing pathway, possibly coming from the medial septum or the hippocampus, may also be important in cingulate theta generation.

Acetylcholinesterase↗

PubMed1987

Hippocampal electrical activity in the diabetes insipidus (Brattleboro) rat.

Theta rhythm was recorded from the hippocampus in normal male and female rats, and from female rats with homozygous alleles (HODI) and heterozygous alleles of diabetes insipidus (HEDI). Second-by-second spectral analysis of the complete period of rapid eye-movement sleep indicated that HODI and HEDI rats had the same theta frequency range as normals, but the mean theta frequency (6.4 cycles c/s) was lower than normal (6.8 c/s), mainly in having a smaller proportion of frequencies greater than or equal to 7.8 c/s. Pharmacological studies in the waking rat demonstrated a theta rhythm in the HODI and normal rats after atropine or after urethane and eserine, indicating the presence of both atropine-sensitive and atropine-resistant pathways. However, after eserine, a huge increase in hippocampal fast waves (30 to 55 c/s) accompanying struggling (as compared with immobility) was found in the HODI rat, which was double that in the normal rat. An enhanced cholinergic input or response at the septal or hippocampal level may account for the large fast wave as well as the lower mean theta frequency in the HODI rat.

Animals↗

PubMed1987

Transcallosal evoked potentials in relation to behavior in the rat: effects of atropine, p-chlorophenylalanine, reserpine, scopolamine and trifluoperazine.

Single pulse electrical stimulation of the sensorimotor cortex in waking rats produced an evoked response in the contralateral sensorimotor cortex. The slow wave response consisted of: (1) an early component that was negative at the pial surface and in layer V, and was associated with multiunit discharge; and (2) a late component that was mainly negative at the surface, positive in layer V, and was associated with multiunit suppression. Previous research suggests that the early component represents summed excitatory postsynaptic potentials; the late component summed inhibitory postsynaptic potentials. Both components could be elicited by direct stimulation of the corpus callosum and both were abolished by midline callosal section. The amplitude and duration of the late component varied with concurrent motor activity in a striking manner. It was large during waking immobility and also during face-washing, licking the paws, chewing food and drinking water, but was much reduced or absent during head movements, walking and changes in posture. Only minor changes were associated with the transition from waking immobility to slow wave sleep. A series of pharmacological experiments indicated that the behavior-related variation in the late component of the transcallosal evoked response was dependent on both cholinergic and serotonergic transmission.

Animals↗

PubMed1985

Topographical projection of cholinergic neurons in the basal forebrain to the cingulate cortex in the rat.

The cholinergic innervation of the rat's posterior cingulate cortex (Brodmann's area 29) was studied using acetylcholinesterase (AChE) histochemistry. Electrolytic lesion of the ipsilateral medial septum and diagonal band region (MS-DB) reduced the diffuse AChE staining in layers I, II, III and V of the cingulate cortex. Kainic acid lesion of the ipsilateral globus pallidus and substantia innominata area (GP-SI) abolished the dense band of AChE stain in layer IV, with small reductions of AChE stain in other layers. The results indicate that the medial cholinergic pathway from MS-DB terminates diffusely in layers I, II, III and V while the lateral cholinergic pathway from the GP-SI predominantly ends in layer IV of the posterior cingulate cortex.

Acetylcholinesterase↗

PubMed1985

Pathways through cingulate, neo- and entorhinal cortices mediate atropine-resistant hippocampal rhythmical slow activity.

Rats prepared with a lesion separating the entorhinal cortex from the neocortex and cingulate cortex displayed apparently normal hippocampal rhythmical slow activity (RSA) with a frequency of 6-12 Hz in both CA1 and dentate gyrus during Type 1 behavior (locomotion, head movements, changes in posture). Variations in the commissural average evoked potential (AEP) and increased power in the 30-100 Hz range (fast waves) also correlated with Type 1 behavior. Urethane did not abolish the RSA. However, systemic administration of atropinic drugs eliminated all RSA and eliminated or attenuated the Type 1 behavior-related variations in the AEP and fast waves. Thus, the normally present atropine-resistant RSA was eliminated by the cortical lesion while atropine-sensitive RSA remained intact. Removal of cingulate cortex alone was partially effective in suppressing atropine-resistant RSA but a lesion of the neocortex only, sparing cingulate cortex, had a minimal effect on it. Lesions of the amygdala, the anterior or medial thalamus or the cerebellum had little or no effect on atropine-resistant RSA. Previous work has shown that lesions of the entorhinal cortex or lateral hypothalamus eliminate atropine-resistant RSA. We suggest that atropine-resistant RSA is mediated by a somewhat diffuse pathway which traverses the hypothalamus, cingulate cortex, and neocortex before reaching the hippocampus via the entorhinal cortex.

Animals↗

PubMed1985

Timing pulse and sampling programs implemented on a laboratory microcomputer.

This paper presents two programs implemented on a microcomputer for analog-to-digital (A-to-D) conversion of neurophysiological signals. The first program, TIMET, sets flexible pulse trains for the timing of the A-to-D conversions, executed by the second program, ADC8. TIMET contains options for a continuous or a triggered pulse train with variable onset delay. ADC8 allows sampling up to 30 kHz for one channel and 9 kHz for the maximum of 7 channels, with about 8 microseconds lag between channels. The digitized data are displayed with interactive gain control from keyboard input, and selected sweeps can be stored on disk files.

Animals↗

PubMed1985

Spectral analysis of hippocampal EEG in the freely moving rat: effects of centrally active drugs and relations to evoked potentials.

Hippocampal EEG signals derived from chronically implanted electrodes in the freely moving rat were recorded before and after administration of centrally acting drugs, and analyzed by power and coherence spectra. Eserine, ether or urethane induced a low frequency (3-6 c/sec) theta power and coherence peak in the immobile rat, which was sensitive to atropine or scopolamine. After phencyclidine, theta that occurred during walking (7-8 c/sec) was virtually abolished by atropine while in the normal rat, absolute theta power was not affected by atropine. The residue spectrum, defined as the EEG spectrum with the theta harmonics removed, was sensitive to centrally acting drugs. Ether, urethane and pentobarbital suppressed fast waves of 50-100 c/sec, and under some conditions, enhanced 15-50 c/sec waves. Eserine enhanced (30-60 c/sec) fast waves during walking while atropine suppressed fast waves and increased irregular slow activity (less than 30 c/sec). The main effects of drugs and behavior on the residue spectra and on the average evoked potentials following stimulation of the Schaffer collaterals could be explained by a previously proposed model (Leung 1982) which suggests a continuum of hippocampal 'activation' (tonic input) under the various conditions.

Anesthetics↗

PubMed1984

Model of gradual phase shift of theta rhythm in the rat.

CA1 pyramidal cell is modeled by a linked series of passive compartments representing the soma and different parts of the dendritic tree. Intracellular postsynaptic potentials are simulated by conductance changes at one or more compartments. By assuming an infinite homogeneous extracellular medium and a particular geometrical arrangement of pyramidal cells, field potential profiles are generated from the current source-sinks of the compartments. The pyramidal cells are driven at the theta (theta)-frequency at different sites of the dendritic tree in order to simulate external driving of hippocampus by the septal cells. Inhibitory or excitatory driving at different sites gives extracellular dipole fields of different null zones and maxima. Phase reversal (180 degrees) of a dipole field generated by synchronous synaptic currents is completed within a depth of 150 micron. By driving two spatially distinct but overlapping dipole fields slightly phase-shifted (30-90 degrees) from each other, the resultant field shows a gradual phase shift of 180 degrees in over 400 micron depth and no (stationary) null zones. The latter field correspond to the theta-profiles seen in the freely moving rat. Somatic inhibition is proposed to be the synaptic process generating the theta-field potentials (named dipole I) in the urethananesthetized or curarized rat. Dipole I has amplitude maxima at the basal dendritic and the distal apical dendritic layers, with a distinct null zone and phase reversal at the apical side of the CA1 pyramidal cell layer. Rhythmic distal dendritic excitation, time-delayed to somatic inhibition, is proposed to be the additional dipole (dipole II) found in freely moving rats. The combination of dipoles I and II, phase-shifted from each other, causes the gradual theta-field phase shift. Experimental studies indicate that dipole I is atropine-sensitive and probably driven by a cholinergic septohippocampal input, whereas dipole II is atropine-resistant and may come from a pathway through both the septum and the entorhinal cortex. Variations of the phase profiles of the theta-field in freely moving rats by administration of anesthetic and cholinergic drugs and by normal changes in theta-frequency could be accounted for by the proposed model. Changes of the intracellular membrane potential, cellular firing rate, and evoked excitability at different phases of the theta-rhythm in anesthetized and freely moving rats can be predicted from the model, and they are in general agreement with the extant literature. In conclusion, theta-field is generated by a rhythmic somatic inhibition phase-shifted with a distal apical-dendritic excitation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1979

Orthodromic activation of hippocampal CA1 region of the rat.

(1) The posterior alveus (PA), the anterior alveus (AA) and the Schaffer collaterals (SCH) evoked field potential components which were organized as parasagittal strips of various widths. Spatially continuous and interactive lamellae are suggested. (2) By correlation with unit activities, the early postsynaptic components evoked by PA, AA and SCH were inferred to be extracellular excitatory postsynaptic potentials (EPSPs) and the late, long-duration components, the inhibitory postsynaptic potentials (IPSPs). The hypothesis that interneurons as well as pyramidal cells generate the field is proposed and discussed. (3) One- and two-dimensional profiles of deep evoked potentials and current source-sink analysis revealed excitatory synapses in stratum oriens for the PA and AA inputs and in stratum radiatum for the SCH input. The late dipole field evoked by PA and AA possessed current sources in strata radiatum and pyramidale, the sites of the inhibitory synapses. The late dipole field evoked by SCH had another component possibly generated by recurrent activity, afterpotentials or relayed activity through CA3.

Animals↗

PubMed1979

Potentials evoked by alvear tract in hippocampal CA1 region of rats. I. Topographical projection, component analysis, and correlation with unit activities.

1. The field potentials and unit activities evoked by the alvear tract (AT) in CA1 region of the dorsal hippocampus of rats were studied under sodium pentobarbital anesthesia. 2. The localized activity evoked anterior to an AT stimulus began as a compound action potential, followed by a slower negative wave, and ended in a long-lasting, slow positive wave. Observed with a 64-electrode recording array, topographical projections of the AT in CA1 were seen as parallel strips inclined at an angle of 5-30 degrees medially from the sagittal plane. 3. Three overlapping components in the averaged evoked potentials (AEPs) were distinguished. The first event (component I) was a brief compound antidromic action potential of pyramidal cells. The second field event (component II) reversed from surface negative to deep positive at 200 micrometer from the ventricular surface, increased rapidly with stimulus intensity, potentiated with double shocks, and followed stimulus frequency up to 50/s. The third component was long lasting (up to 200 ms), surface positive and ventral negative (turnover at 150 micron below the pyramidal layer), followed stimulus frequency up to about 10/s, and saturated at a low stimulus intensity (about 3 x threshold). 4. In some preparations, another fast negative peak of about 2 ms duration was found to follow the axon compound action potential on the hippocampal surface and appeared to propagate from the pyramidal layer to the ventricular surface. It was probably of nonsynaptic origin, perhaps due to the centrifugal basal dendritic spikes of the pyramidal cells. 5. Single units were recorded in CA1. Antidromic units were identified by their firing at a fixed latency (1.5 ms) and ability to follow high stimulus frequencies. Units firing at about 2.7 ms latency possessed characteristics of monosynaptic excitation. Under light anesthesia, many of the latter units also showed a late, prolonged suppression of background firing. Tentative interneuronal types fired with peak latencies of 4-5 ms or showed prolonged increase in firing rate. 6. From the correlation with unit post-stimulus time histograms, AEP component II was inferred to be the extracellular, monosynaptic, excitatory postsynaptic potentials, and component III the di- or polysynaptic inhibitory postsynaptic potentials. These postsynaptic potentials were generated by the pyramidal cells and interneurons.

Animals↗