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L Stan Leung

Publications and source records attributed to L Stan Leung.

At least 19 recordsLinked to original sources
PubMed2007

The supramammillo-septal-hippocampal pathway mediates sensorimotor gating impairment and hyperlocomotion induced by MK-801 and ketamine in rats.

RATIONALE: Ketamine or MK-801 induced sensorimotor gating deficit, but the underlying neural mechanisms are not completely known. We have previously demonstrated that the medial septum (MS) mediated the phencyclidine-induced deficit in prepulse inhibition of the acoustic startle (PPI) in rats. OBJECTIVES: We investigated the involvement of the supramammillary area (SUM) to MS pathway in PPI impairment and behavioral hyperlocomotion induced by MK-801 or ketamine in rats and correlated the behavioral deficits with hippocampal gamma wave increase. MATERIALS AND METHODS: Ketamine (6 mg/kg, s.c.) or MK-801 (0.5 mg/kg, i.p.) was administered after infusion of saline or the GABA(A) receptor agonist, muscimol (0.25 microg), into the MS or SUM. Locomotion, PPI, and hippocampal electroencephalogram (EEG) were recorded. RESULTS: MK-801 or ketamine induced PPI impairment and behavioral hyperlocomotion, accompanied by an increase in hippocampal gamma waves (30-100 Hz). The changes in behavior and gamma waves induced by ketamine or MK-801 were antagonized by pre-infusion of muscimol, but not saline, into the SUM or MS. Infusion of muscimol into the SUM alone did not significantly affect PPI, but it suppressed spontaneous locomotor behavior and hippocampal EEG. Infusion of ionotropic glutamate receptor antagonists into the MS did not affect the PPI deficit or the gamma wave increase after MK-801. CONCLUSIONS: A non-glutamatergic component of the supramammillo-septal pathway mediates the hyperlocomotion and the deficits in PPI induced by MK-801 or ketamine. Inactivation of the MS or SUM normalized both the hippocampal gamma waves and the behavioral deficits (PPI impairment and hyperlocomotion).

Acoustic Stimulation↗
PubMed2006

Hippocampal partial kindling decreased hippocampal GABAB receptor efficacy and wet dog shakes in rats.

To test the hypothesis that GABA(B) receptor efficacy in the behaving rat decreases after partial hippocampal kindling, we measured GABA(B) receptor efficacy by the number of wet dog shakes (WDSs) induced by baclofen (5mM in 0.2muL of saline) infusion into the dorsal hippocampus; these WDSs were blocked by prior infusion of GABA(B) receptor antagonist CGP55845A. Rats were given 15 afterdischarges (ADs) evoked in CA1 over 3 days or control stimulations. The partially kindled rats (after 15 ADs) showed a significant decrease in baclofen-induced WDSs as compared to control rats, on days 1, 4 and 21 after kindling. In contrast, kindled and control rats did not show a significant difference in WDSs induced by hippocampal infusion of GABA(A) receptor antagonist bicuculline. Also, the number of WDSs induced after subcutaneous injection of serotonin-2A/2C agonist+/-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane was not different between kindled and control rats on 4 and 21 days after kindling. We further tested the hypothesis that the decrease in hippocampal AD-induced WDSs during kindling is caused by a decrease in GABA(B) receptor efficacy. However, we found no convincing evidence to support the latter hypothesis since the AD-induced WDSs were not suppressed by hippocampal infusion of CGP55845A, with the exception that CGP55845A infusion into ventral hippocampus suppressed both hippocampal ADs and WDSs. Together with results derived from previous electrophysiological studies in vitro, it is suggested that a decrease of GABA(B) receptor, possibly GABA(B) autoreceptor, efficacy may explain the decrease of baclofen-induced WDSs after hippocampal kindling.

Amphetamines↗
PubMed2006

Presynaptic GABA(B) receptors on glutamatergic terminals of CA1 pyramidal cells decrease in efficacy after partial hippocampal kindling.

We tested the hypothesis that presynaptic GABA(B) receptors on glutamatergic terminals (GABA(B) heterosynaptic receptors) decreased in efficacy after partial hippocampal kindling. Rats were implanted with chronically indwelling electrodes and 15 hippocampal afterdischarges were evoked by high-frequency electrical stimulation of hippocampal CA1. Control rats were implanted with electrodes but not given high-frequency stimulations. One to 21 days after the last afterdischarge, excitatory postsynaptic potentials (EPSPs) were recorded in CA1 of hippocampal slices in vitro, following stimulation of the stratum radiatum. Field EPSPs (fEPSPs) were recorded in CA1 stratum radiatum and intracellular EPSPs (iEPSPs) were recorded from CA1 pyramidal cells. GABA(B) receptor agonist +/- baclofen (10 microM) in the bath suppressed the fEPSPs significantly more in control than kindled rats, at 1 or 21 days after kindling. Similarly, baclofen (10 microM) suppressed iEPSPs more in the control than the kindled group of neurons recorded at 1 day after kindling. Suppression of the fEPSPs by 1 microM N(6)-cyclopentyladenosine, which acted on presynaptic A1 receptors, was not different between kindled and control rats. Activation of the GABA(B) heteroreceptors by a conditioning burst stimulation of CA3 afferents suppressed the iEPSPs evoked by a test pulse. The suppression of the iEPSPs at 250-500 ms condition-test interval was larger in control than kindled groups of neurons. It was concluded that the efficacy of presynaptic GABA(B) receptors on the glutamatergic terminals was reduced after partial hippocampal kindling. The reduction in heterosynaptic presynaptic GABA(B) receptor efficacy will increase glutamate release and seizure susceptibility, particularly during repeated neural activity.

Adenosine↗
PubMed2006

Linear aspects of transformation from interictal epileptic discharges to BOLD fMRI signals in an animal model of occipital epilepsy.

Epileptic disorders manifest with seizures and interictal epileptic discharges (IEDs). The hemodynamic changes that accompany IEDs are poorly understood and may be critical for understanding epileptogenesis. Despite a known linear coupling of the neurovascular elements in normal brain tissues, previous simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies have shown variable correlations between epileptic discharges and blood oxygenation level-dependent (BOLD) response, partly because most previous studies assumed particular hemodynamic properties in normal brain tissue. The occurrence of IEDs in human subjects is unpredictable. Therefore, an animal model with reproducible stereotyped IEDs was developed by the focal injection of penicillin into the right occipital cortex of rats anesthetized with isoflurane. Simultaneous EEG-fMRI was used to study the hemodynamic changes during IEDs. A hybrid of temporal independent component analysis (ICA) of EEG and spatial ICA of fMRI data was used to correlate BOLD fMRI signals with IEDs. A linear autoregression with exogenous input (ARX) model was used to estimate the hemodynamic impulse response function (HIRF) based on the data from simultaneous EEG-fMRI measurement. Changes in the measured BOLD signal from the right primary visual cortex and bilateral visual association cortices were consistently coupled to IEDs. The linear ARX model was applied here to confirm that a linear transform can be used to study the correlation between BOLD signal and its corresponding neural activity in this animal model of occipital epilepsy.

Animals↗
PubMed2006

Hippocampal CA1 kindling but not long-term potentiation disrupts spatial memory performance.

Long-term synaptic enhancement in the hippocampus has been suggested to cause deficits in spatial performance. Synaptic enhancement has been reported after hippocampal kindling that induced repeated electrographic seizures or afterdischarges (ADs) and after long-term potentiation (LTP) defined as synaptic enhancement without ADs. We studied whether repeated stimulations that gave LTP or ADs resulted in spatial performance deficits on the radial arm maze (RAM) and investigated the minimal number of ADs required for such deficits. Three experimental groups were run as follows: (1) 5 hippocampal ADs in 1 d (5-AD group), (2) 10 hippocampal ADs in 2 d (10-AD group), and (3) 12 -frequency primed-burst stimulations (PBSs) in 2 d in order to induce LTP without ADs (LTP group). Each experimental group was run together with a control group during the same time period. Rats were first trained in a spatial task on a radial arm maze with four of the eight arms baited, then given control or experimental treatment, and maze performance was tested in the first week (1-4 d) and fourth week (22-25 d) after treatment. Basal dendritic population excitatory postsynaptic potentials (pEPSPs) and medial perforant path (MPP)-evoked dentate gyrus population spike and polysynaptic CA1 excitation were recorded before and after experimental and control treatment. Spatial memory errors, in particular reference memory errors, were significantly higher in the 10-AD kindled group than any other group on the first and fourth week after treatment. Spatial memory errors were not significantly different in the 5-AD and LTP groups as compared with any control groups at any time. Basal dendritic pEPSP in CA1 was enhanced for about 1 wk after 12 PBSs, 10 ADs, or 5 ADs, while the dentate gyrus population spike and CA1 polysynaptic excitation evoked by MPP was increased for up to 4 wk after 10 ADs, but not 12 PBSs. Thus, distributed alteration of multiple synaptic transmission in the entorhinal-hippocampal circuit, but not LTP at the basal dendritic synapses in CA1, may disrupt spatial performance after 10 hippocampal ADs.

Animals↗
PubMed2006

GABA(B) receptors inhibit backpropagating dendritic spikes in hippocampal CA1 pyramidal cells in vivo.

Spike backpropagation has been proposed to enhance dendritic depolarization and synaptic plasticity. However, relatively little is known about the inhibitory control of spike backpropagation in vivo. In this study, the backpropagation of the antidromic spike into the dendrites of CA1 pyramidal cells was studied by extracellular recording in urethane-anesthetized rats. The population antidromic spike (pAS) in CA1 following stimulation of the alveus was recorded simultaneously with a 16-channel silicon probe and analyzed as current source density (CSD). The pAS current sink was shown to sequentially invade the soma and then the apical and basal dendrites. When the pAS was preceded <400 ms by a conditioning orthodromic CA3 stimulus, the apical and basal dendritic spike sinks were reduced and delayed. Dendritic spike suppression was large after a high-intensity CA3 conditioning stimulus that evoked a population spike, small after a low-intensity CA3 conditioning stimulus, and weak after conditioning by another pAS. The late (150-400 ms latency) inhibition of the backpropagating pAS at the apical and basal dendrites was partially relieved by a GABA(B) receptor antagonist, CGP35348 or CGP56999A, given intracerebroventricularly (icv). CGP35348 icv also decreased the latency of the antidromic spike sinks at all depths. A compartment cable model of a CA1 pyramidal cell with excitable dendrites, combined with a model of extracellular potential generation, confirms that GABA(B) receptor activation delays a backpropagating spike and blocks distal dendritic spikes. GABA(B) receptor-mediated conductance increase and hyperpolarization, amplified by removing dendritic I(A) inactivation, contribute to conditioned dendritic spike suppression. In addition, the model shows that slow Na(+) channel inactivation also participates in conditioned spike suppression, which may partly explain the small dendritic spike suppression after conditioning with a weak orthodromic stimulus or another antidromic spike. Thus, both theory and experiment confirm an important role of the GABA(B) receptors in controlling dendritic spike backpropagation.

Animals↗
PubMed2006

Limbic system participates in mediating the effects of general anesthetics.

In a previous study, we reported that inactivation of the medial septum or the hippocampus by muscimol, a GABA(A) receptor agonist, potentiated the effects of a general anesthetic. In this study, we further investigated whether other structures that are connected to the septohippocampal system are involved in mediating general anesthesia. In freely behaving rats, muscimol (0.25 microg) or saline was infused intracerebrally into one of four areas-the supramammillary area (SUM), nucleus accumbens (NAC), ventral pallidum (VP), and ventral tegmental area (VTA)-and righting, pain, and EEG responses were recorded following either halothane or sodium pentobarbital, representing inhalational and injectable general anesthetic, respectively. The effect of halothane (2%) or pentobarbital (20 mg/kg i.p.) in abolishing the righting, pain response, or low-voltage neocortical activity was enhanced, and the initial behavioral hyperactivity (delirium) was reduced, after muscimol as compared to after saline infusion in SUM, NAC, VP, and VTA. EEGs in the hippocampus and the sensorimotor cortex following halothane or pentobarbital showed increased delta, and decreased hippocampal theta and gamma waves after muscimol infusion as compared to saline infusion in SUM, NAC, VP, and VTA. By contrast, infusion of muscimol in the median raphe increased locomotion and did not significantly alter the behavioral or EEG effects of halothane or pentobarbital. It is suggested that structures that activate the limbic cortices (MS, SUM, and VTA but not the median raphe) or mediate the output of the hippocampus (NAC and VP) normally participate in maintaining consciousness and inactivation of these structures potentiates the response to a general anesthetic.

Anesthetics↗
PubMed2006

Decrease of hippocampal GABA B receptor-mediated inhibition after hyperthermia-induced seizures in immature rats.

PURPOSE: Whether febrile seizures have detrimental consequences on the brain is still controversial. We hypothesized that neuronal inhibition in the hippocampus is altered after hyperthermia-induced seizures in immature rats. METHODS: Rats were given a single seizure by a heat lamp on postnatal day (PND) 15, or repeated seizures by heated air on PND 13 to 15. Fourteen or 30 days after the seizure(s), laminar field potentials were recorded by 16-channel silicon probes in CA1 and the dentate gyrus (DG), in response to the paired-pulse stimulation of the CA3 and medial perforant path, and analyzed as current source density. Gamma-aminobutyric acid (GABA)(B)-receptor antagonist CGP35348 was injected intracerebroventricularly (icv). RESULTS: At 14 but not at 30 days after a single or after repeated hyperthermia-induced seizures, paired-pulse facilitation (PPF) of the CA1 population spikes at 100 to 200 ms interpulse intervals (IPIs) was significantly increased in seizure as compared with control rats, irrespective of the types of induced seizures. CGP35348 icv also resulted in PPF at 100 to 200 ms IPIs in CA1 of control rats, but CGP35348 had no effect on PPF in seizure rats. At 30 days after repeated seizures, paired-pulse inhibition in the DG was significantly increased at 30-ms IPI, and PPF was increased at 200-ms IPI. CGP35348 increased paired-pulse inhibition in the DG in repeated-seizure rats but not in control rats. CONCLUSIONS: We conclude that hyperthermia-induced seizures in immature rats induced a decrease of GABA(B) receptor-mediated inhibition in CA1 and DG that lasted > or =14 to 30 days after hyperthermic seizure(s).

Animals↗
PubMed2005

Physiological monitoring of small animals during magnetic resonance imaging.

Maintaining a stable physiologic state is essential when studying animal models of epilepsy with simultaneous electroencephalograph (EEG) and functional magnetic resonance imaging (fMRI) or EEG and magnetic resonance spectroscopy (MRS). To achieve and maintain such stability in rats in the MRI environment, a minimally invasive but comprehensive system was developed to monitor body temperature, heart rate, blood pressure, blood oxygen saturation and end-tidal CO2 (ETCO2) of expired gas. All physiologic parameters were successfully monitored in Sprague-Dawley rats without interfering with EEG recordings during simultaneous fMRI and MRS studies. Body temperature, heart rate, blood pressure, blood oxygen saturation, and ETCO2, were maintained between 36.5 and 37.5 degrees C, 250-450 beats/min, 136+/-17 mmHg, >90%, and 20-35 mmHg, respectively for 6-8 h under inhalational anesthesia. This set-up could be extended to study in vivo applications in other laboratory animals with only minor modifications.

Anesthetics, Inhalation↗
PubMed2005

Real-time display of artifact-free electroencephalography during functional magnetic resonance imaging and magnetic resonance spectroscopy in an animal model of epilepsy.

Simultaneous recording of electroencephalogram (EEG) and functional MRI (fMRI) or MR spectroscopy (MRS) can provide further insight into our understanding of the underlying mechanisms of neurologic disorders. Current technology for simultaneous EEG and MRI recording is limited by extensive postacquisition processing of the data. Real-time display of artifact-free EEG recording during fMRI/MRS studies is essential in studies that involve epilepsy to ensure that they address specific EEG features such as epileptic spikes or seizures. By optimizing the EEG recording equipment to maximize the common mode rejection ratio of its amplifiers, a unique EEG system was designed and tested that allowed real-time display of the artifact-free EEG during fMRI/MRS in an animal model of epilepsy. Spike recordings were optimized by suppression of the background EEG activity using fast-acting and easily controlled inhalational anesthesia. Artifact suppression efficiency of 70-100% was achieved following direct subtraction of referentially recorded filtered EEG tracings from active electrodes, which were located in close proximity to each other (over homologous occipital cortices) and a reference electrode. Two independent postacquisition processing tools, independent component analysis and direct subtraction of unfiltered digital EEG data in MATLAB, were used to verify the accuracy of real-time EEG display.

Algorithms↗
PubMed2005

Hippocampal melatonin receptors modulate seizure threshold.

PURPOSE: The pineal hormone melatonin has been shown to enhance hippocampal excitability. We therefore investigated whether inactivation of hippocampal melatonin receptors affects behavioral seizures. METHODS: Intrahippocampal infusions were performed in rats to study the effect of different melatonin receptor antagonists on behavioral activity, EEG, and seizure susceptibility. Experiments were conducted at 2 times of the day that coincided with the peak and trough of the daily melatonin rhythm. RESULTS: Local infusion of the Mel(1b) receptor antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT) into the hippocampus, but not the overlying neocortex, significantly increased seizure latency and in some cases provided complete protection against seizure development. In addition, 4-P-PDOT suppressed open field activity and hippocampal EEG amplitude. The mixed Mel(1a)/Mel(1b) receptor antagonist luzindole also increased seizure latency but to a lesser degree than 4-P-PDOT. The behavioral effects of Mel(1b) receptor inhibition were comparable to those of the gamma-aminobutyric acid (GABA)(A) receptor agonist muscimol and were observed during the dark phase (2400-0200 h) but not the light phase (1200-1400 h) of the daily photocycle. The anticonvulsant effect of intrahippocampal infusion of 4P-P-DOT was blocked by coadministration of the GABA(A) antagonist bicuculline. CONCLUSIONS: Our results suggest that nocturnal activation of hippocampal Mel(1b) receptors depresses GABA(A) receptor function in the hippocampus and enhances seizure susceptibility.

Animals↗
PubMed2005

Hippocampal afterdischarges after GABA(B)-receptor blockade in the freely moving rat.

PURPOSE: To determine whether hippocampal afterdischarges (ADs) and excitability changes were induced by gamma-aminobutyric acid (GABA)(B)-receptor blockade in adult, freely moving rats. METHODS: A specific GABA(B)-receptor antagonist CGP35348, CGP55845A, or CGP55699A was injected intracerebroventricularly (i.c.v.), and EEGs and behaviors of rats were analyzed. RESULTS: CGP35348 (56-110 microg, i.c.v.) induced afterdischarges (ADs) approximately 60% of the time, starting at the hippocampus or neocortex. Neocortical-onset ADs began with sporadic discharges and were <3 mV. Hippocampal-onset ADs were bilateral, >5 mV, and spread to the entorhinal cortex and amygdala, often ending in a rebound AD and accompanied with stereotypic jumping, forelimb clonus, and wet-dog shakes. The CGP35348-induced hippocampal AD had an onset frequency (5-9 Hz) that was higher than the electrically evoked AD (2-4 Hz). CGP35348 i.c.v. also increased the mean starting frequency of an electrically evoked hippocampal AD from 3.6 Hz to 5.3 Hz. Hippocampal gamma activity (25-80 Hz) increased up to twofold for 30 min after a hippocampal but not a neocortical AD. A single dose of CGP35348 induced repeated ADs of increasing duration. Paired-pulse inhibition of the evoked potentials in CA1, at interpulse interval of <100 ms, was decreased after but not before a hippocampal AD. CGP56999A (i.c.v.) gave results similar to those with CGP35348, whereas CGP55845A (i.c.v.) rarely induced ADs. CONCLUSIONS: GABA(B)-receptor blockade increases seizure susceptibility by reducing AD threshold and increasing the frequency and spread of a hippocampal AD. Hippocampal excitability (based on paired-pulse test) and gamma activity increased after but not before a hippocampal AD.

Animals↗
PubMed2004

The medial septum mediates impairment of prepulse inhibition of acoustic startle induced by a hippocampal seizure or phencyclidine.

The involvement of the septohippocampal system on the impaired sensorimotor gating induced by phencyclidine (PCP) or by an electrically induced hippocampal seizure was examined in behaving rats. An impaired sensorimotor gating, measured by prepulse inhibition (PPI) of the acoustic startle response, was observed following a hippocampal afterdischarge (AD) or systemic injection of PCP and was accompanied with an increase in hippocampal gamma waves (30-70 Hz). The medial septum infusion with muscimol (0.25 microg), a GABA(A) receptor agonist, 15 min prior to PCP or a hippocampal AD, prevented the impairment of sensorimotor gating and the increase in gamma waves. By itself, muscimol (0.25 microg) injection into the medial septum did not affect PPI, although it significantly suppressed spontaneous gamma waves. In order to identify subpopulations of neurons mediating the sensorimotor gating deficit and the hippocampal gamma wave increase, 0.14-0.21 microg of p75 antibody conjugated to saporin (192 IgG-saporin) was injected into the medial septum to selectively lesion the septohippocampal cholinergic neurons. Neither the PPI deficit nor the gamma wave increase induced by PCP or a hippocampal AD was affected by 192 IgG-saporin lesion of the medial septum. It is concluded that increase in neural activity in the medial septum participates in the impairment of sensorimotor gating and the increase in hippocampal gamma waves induced by PCP or a hippocampal AD. It is suggested that the GABAergic but not the cholinergic septohippocampal neurons mediate the sensorimotor gating deficit.

Animals↗
PubMed2004

Sodium-activated potassium conductance participates in the depolarizing afterpotential following a single action potential in rat hippocampal CA1 pyramidal cells.

The depolarizing afterpotential (DAP) following an action potential increases the excitability of a neuron. Mechanisms related to the DAP following an antidromic or current-induced spike were studied in CA1 pyramidal cells by whole-cell recordings in hippocampal slices in vitro. In DAP-holding voltage curves, the DAP at 10 ms after the spike peak (DAP10) was extrapolated to reverse at about -50 mV. Increase of extracellular K(+) concentration increased DAP and neuronal bursting. DAP10 reversal potential shifted positively with an increase in [K(+)](o) and with the blockade of K(+) conductance using pipettes filled with Cs(+). Similarly, extracellular tetraethylammonium (TEA; 10 mM), 4-aminopyridine (3-10 mM) increased DAP and shifted the DAP10 reversal potential to a depolarizing direction. Decrease of [Ca(2+)](o) did not alter DAP significantly, suggesting a nonessential role of Ca(2+) in the DAP. Perfusion of tetrodotoxin (TTX; 0.1-1 microM) and replacement of extracellular Na(+) by choline(+) suppressed both spike height and DAP simultaneously. Replacement of extracellular Na(+) by Li(+) increased DAP and spike bursts, and caused a positive shift of the DAP10 reversal potential. It is suggested that Li(+) increased DAP by blocking an Na(+)-activated K(+) current. In summary, multiple K(+) conductances are normally active during the DAP following a single action potential.

4-Aminopyridine↗
PubMed2004

Schizophrenia-like behavioral changes after partial hippocampal kindling.

The effect of hippocampal kindling on behavioral changes following 10 and 21 hippocampal afterdischarges (ADs) or electrographic seizures was examined in behaving rats. As compared to control, non-stimulated rats, 21 but not 10 hippocampal ADs resulted in a decrease in social contact, an increase in social isolation, and an increase in climbing and chasing behavior tested in an open field 3 days after cessation of kindling. Porsolt forced swimming test was not different among the control, 10- or 21-AD groups of rats. A deficit in sensorimotor gating, measured by prepulse inhibition of an acoustic startle, was observed in kindled as compared to control rats at 2 weeks after 21 ADs, but not after 10 ADs. Similarly, methamphetamine (1 mg/kg i.p.) induced higher locomotor activity in kindled rats, as compared to controls, after 21 ADs but not after 10 ADs. Spontaneous locomotor activity in a novel cage, without drug administration, was not different between kindled and control rats. These findings suggest that behavioral alterations after repeated hippocampal electrographic seizures may be mediated by increased dopaminergic functions, which may also mediate the psychiatric symptoms in human epileptic patients.

Acoustic Stimulation↗
PubMed2004

Glutamatergic synaptic transmission participates in generating the hippocampal EEG.

The participation of ionotropic glutamatergic synapses in the generation of hippocampal electroencephalography (EEG) of behaving rats has not been systematically studied. In this study, field potentials in hippocampal CA1 were recorded following injection of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, or vehicle control, either into the lateral ventricles or directly into the hippocampus or the medial septum. Intraventricular (i.c.v.) AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX, 5-10 microg) decreased the commissural evoked potential and the amplitude of the hippocampal EEG, including the theta rhythm. Theta frequency was decreased by 10 microg, but not 5 microg DNQX i.c.v. Unilateral intrahippocampal injection of DNQX (5 microg) only decreased the amplitude, but not the frequency, of the theta rhythm near the site of injection, without affecting theta amplitude or frequency at the opposite hippocampus. Other than theta, the large irregular activity (with a delta frequency peak at 1-2 Hz) and gamma EEG (30-100 Hz) were also decreased by i.c.v. and intrahippocampal injections of DNQX. Intrahippocampal injection of NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV, 2.5 microg) decreased the amplitude of the theta rhythm and, less consistently, the gamma EEG. The frequency of the theta rhythm and the peak of the commissural evoked potential were not significantly affected by intrahippocampal D-APV injection. Medial septal injections of D-APV or D,L-APV (2.24 microg in 0.4 microl), but not DNQX (10 microg in 0.4 microl), decreased the amplitude of the hippocampal theta significantly, but theta frequency was not significantly affected. It is concluded that both NMDA and AMPA receptors in the hippocampus are involved in generating the amplitude of the hippocampal EEG of theta and gamma frequencies, while NMDA receptors in the medial septum are involved in controlling the amplitude of theta and gamma EEG in the hippocampus. Excitatory glutamatergic synaptic currents, activated by afferents from the entorhinal cortex and CA3, are suggested to participate in hippocampal EEG activities.

Animals↗
PubMed2003

Cholinergic activity enhances hippocampal long-term potentiation in CA1 during walking in rats.

Long-term potentiation (LTP) at the basal-dendritic synapses of CA1 pyramidal cells was induced by a single 200 Hz stimulation train (0.5-1 sec duration) in freely behaving rats during one of four behavioral states: awake-immobility (IMM), walking, slow-wave sleep (SWS), and rapid eye movement sleep (REM). Field EPSPs generated by basal-dendritic excitation of CA1 were recorded before and up to 1 d after the tetanus. After a tetanus during any behavioral state, basal-dendritic LTP was >170% of the baseline for the first hour after the tetanus and decayed to approximately 120% 1 d after. LTP induced during walking was significantly larger than that induced during IMM, SWS, or REM, which had similar LTP magnitudes. To test the hypothesis that septohippocampal cholinergic activity enhanced LTP during walking as compared with IMM, rats were either pretreated with muscarinic cholinergic antagonist scopolamine or injected with IgG192-saporin in the medial septum to selectively lesion cholinergic septohippocampal neurons. Pretreatment with scopolamine decreased the LTP induced during walking but did not affect that induced during IMM, such that the difference between the LTP induced during walking and IMM was abolished after scopolamine. Rats injected with IgG192-saporin showed no difference in the LTP induced during walking and IMM, and scopolamine did not reduce the LTP during walking. In contrast, sham-lesion rats showed larger LTP induced during walking than IMM, and the LTP induced during walking was attenuated by scopolamine. This is the first demonstration of an enhancement of hippocampal LTP by physiologically activated cholinergic inputs.

Animals↗