Role of preoperative prediction of microvascular invasion in hepatocellular carcinoma based on the texture of FDG PET image: A comparison of quantitative metabolic parameters and MRI.

Objective: To investigate the role of prediction microvascular invasion (mVI) in hepatocellular carcinoma (HCC) by 18F-FDG PET image texture analysis and hybrid criteria combining PET/CT and multi-parameter MRI. Materials and methods: Ninety-seven patients with HCC who received the examinations of MRI and 18F-FDG PET/CT were retrospectively included in this study and were randomized into training and testing cohorts. The lesion image texture features of 18F-FDG PET were extracted using MaZda software. The optimal predictive texture features of mVI were selected, and the classification procedure was conducted. The predictive performance of mVI by radiomics classier in training and testing cohorts was respectively recorded. Next, the hybrid model was developed by integrating the 18F-FDG PET image texture, metabolic parameters, and MRI parameters to predict mVI through logistic regression. Furthermore, the diagnostic performance of each time was recorded. Results: The 18F-FDG PET image radiomics classier showed good predicted performance in both training and testing cohorts to discriminate HCC with/without mVI, with an AUC of 0.917 (95% CI: 0.824-0.970) and 0.771 (95% CI: 0.578, 0.905). The hybrid model, which combines radiomics classier, SUVmax, ADC, hypovascular arterial phase enhancement pattern on contrast-enhanced MRI, and non-smooth tumor margin, also yielded better predictive performance with an AUC of 0.996 (95% CI: 0.939, 1.000) and 0.953 (95% CI: 0.883, 1.000). The differences in AUCs between radiomics classier and hybrid classier were significant in both training and testing cohorts (DeLong test, both p < 0.05). Conclusion: The radiomics classier based on 18F-FDG PET image texture and the hybrid classier incorporating 18F-FDG PET/CT and MRI yielded good predictive performance, which might provide a precise prediction of HCC mVI preoperatively.

Long-lasting disruption of spatial memory by GABAB receptor antagonist induced seizures.

The objective of this project was to test whether a drug-induced model of temporal lobe seizures, namely seizures induced by a gamma aminobutyric acid (GABAB) receptor antagonist, CGP35348, result in long-term disruption of hippocampal memory function. Seizures were induced in experimental rats by intracerebroventricular (i.c.v.) injection of CGP35348 (0.64 µmol in 3 µL) for three consecutive days; control rats received no injection. Rats were first trained to criterion on an open radial arm maze (RAM) with 4 of the 8 arms baited, then received seizure and control treatment, and tested again on the RAM during the first week (days 1-5) and fourth week (days 22-29) after the last injection. An initial i.c.v. CGP35348 injection induced a mean of 4.4 seizures in the hippocampus, often accompanied with stages 3-5 convulsions, and sometimes with jumping; three daily CGP35348 injections induced 10.4 ±â€¯1.8 (n = 7 rats) seizures in total. In two separate experiments, seizure-treated rats performed worse than control rats in working memory (WM) during both the 1st and 4th weeks after seizures. Reference memory (RM) deficit during the 1st week after seizures was observed in only one experiment in which RM was acquired >2 weeks ago. The memory deficits were not accompanied by gross neuronal loss in the hippocampus. In conclusion, i.c.v. injection of a GABAB receptor antagonist in adult rats induced brief, multiple, focal hippocampal seizures that induced deficits in spatial memory for up to 4 weeks.

3D contrast enhancement-MR angiography for imaging of unruptured cerebral aneurysms: a hospital-based prevalence study.

BACKGROUND AND PURPOSE: Contrast enhanced MRA (CE-MRA) can help to overcome the limitations of other techniques to clearly display the details of cerebral aneurysms at 1.5-T MR system. We investigated the prevalence of unruptured cerebral aneurysms (UCAs) using three dimensional (3D) CE-MRA in a tertiary comprehensive hospital in China. MATERIALS AND METHODS: The cases were prospectively recorded at our hospital between February 2009 and October 2010. 3D CE-MRA, interpreted by 2 observers blinded to the participants' information, was used to identify the location and size of UCAs and to estimate the overall, age-specific, and sex-specific prevalence. RESULTS: Of the 3993 patients (men: women = 2159:1834), 408 UCAs were found in 350 patients (men: women = 151:199). The prevalence was 8.8% overall (95% CI, 8.0-10.0%), with 7.0% for men (CI, 6.0-8.0%) and 10.9% for women (CI, 9.0-12.0%). The overall prevalence of UCAs was higher in women than in men (P<0.001) and increased with age both in men and women. Prevalence peaked at age group 75-80 years. Forty-two patients (11.7%) had multiple aneurysms, including 10 (2.9%) male patients and 32 (9.1%) female patients. The most common site of aneurysm was the carotid siphon, and most lesions (71.3%) had a maximum diameter of 3-5 mm. CONCLUSION: This hospital-based prevalence study suggested a high prevalence (8.8%) of UCAs and most lesions (71.3%) had a maximum diameter of 3-5 mm observed by 3D CE-MRA. Because the rupture of small cerebral aneurysms was not uncommon, an appropriate follow-up care strategy must be formulated.

Medial septal lesion enhances general anesthesia response.

Electrolytic lesion of the medial septum, a basal forebrain nucleus that projects to the hippocampus, prolonged the emergence from general anesthesia in rats. Septal lesioned rats required a longer time to recover from a loss of righting reflex (LORR) and a loss of tail-pinch response after injectable (20 mg/kg i.p. pentobarbital, 5mg/kg i.v. propofol) or volatile (1.5% halothane, 2% isoflurane) anesthetic. When incremental doses of propofol were given i.p., septal lesioned rats as compared to control rats showed LORR at a lower dose of propofol. Similarly, when the rats were exposed to increasing concentrations of isoflurane, the percent of rats showing LORR was leftward shifted for lesioned rats as compared to control rats. Septal lesioned rats as compared to control rats showed decreased locomotor activity when exposed to 1.5% halothane. Lesion of the medial septum was confirmed by thionin-stained histological sections as well as loss of acetylcholinesterase (AchE) staining in the hippocampus, indicating a depletion of septohippocampal cholinergic afferents. Medial septal lesion resulted in a near complete loss of hippocampal theta rhythm during walking and a general decrease in power of the hippocampal EEG at all frequencies (0-100 Hz), during walking or immobility. It is concluded that lesion of medial septum, in part through a loss of septohippocampal cholinergic afferents, increased the anesthesia response to volatile and injectable general anesthetics, during both induction and emergence. It is suggested that the septohippocampal system participates in many components of general anesthesia including hypnosis, immobility, and analgesia.

Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics.

Acetylcholine in the brain has been associated with consciousness and general anesthesia effects. We tested the hypothesis that the integrity of the nucleus basalis magnocellularis (NBM) affects the response to general anesthetics. Cholinergic neurons in NBM were selectively lesioned by bilateral infusion of 192IgG-saporin in adult, male Long-Evans rats, and control rats were infused with saline. Depletion of choline-acetyltransferase (ChAT)-immunoreactive cells in the NBM and decrease in optical density of acetylcholinesterase (AChE) staining in the frontal and visual cortices confirmed a significant decrease in NBM cholinergic neurons in lesioned as compared to control rats. AChE staining in the hippocampus and ChAT-positive neurons in the medial septum-vertical limb of the diagonal band were not different between lesioned and control rats. When a general anesthetic was administered, lesioned compared to control rats showed significantly longer duration of loss of righting reflex (LORR) after propofol (5 or 10mg/kg i.v.), pentobarbital (20 or 40 mg/kg i.p.) but not halothane (2%). However, the behavioral excitation, as indicated by horizontal movements, induced by halothane was reduced in lesioned as compared to control rats. Reversible inactivation of NBM with GABA(A) receptor agonist muscimol increased slow waves in the neocortex during awake immobility, and prolonged the duration of LORR and loss of tail-pinch response after propofol, pentobarbital and halothane. In summary, lesion of NBM cholinergic neurons or inactivation of the NBM prolonged the LORR response to general anesthetic drugs.

Pilocarpine model of temporal lobe epilepsy shows enhanced response to general anesthetics.

Complex partial seizures, commonly arising from temporal lobe epilepsy (TLE), are associated with neuronal loss and post-seizure impairment of consciousness. We tested the hypothesis that TLE subjects, in between seizures, are associated with a decreased level of consciousness that is manifested by an enhanced response to a general anesthetic. Two animal models of TLE--amygdala kindling and pilocarpine-induced status epilepticus (Pilo-SE)--were tested. Pilo-SE rats, but not amygdala-kindled rats, showed a prolonged loss of pain and righting responses after 20 and 40 mg/kg i.p. pentobarbital, 2% halothane, and 5 and 10 mg/kg i.v. propofol as compared to control saline-treated rats. Since the major pathology of Pilo-SE rats was cell loss in the piriform cortex (PC) and the entorhinal cortex (EC), we studied the anesthetic response after inactivation of the EC or PC by locally infusing GABAA receptor agonist muscimol. Muscimol inactivation of the PC or EC, as compared to saline infusion in the same rats, prolonged the duration of loss of righting reflex, typically without changing the duration of loss of tail-pinch response, after 20 mg/kg i.p. pentobarbital, 2% halothane and 5 mg/kg i.v. propofol. Muscimol infusion, as compared to saline infusion, in the PC or EC also tended to decrease 30-100 Hz gamma EEG in the frontal cortex. In conclusion, a TLE model that resulted in neuronal loss, Pilo-SE, enhanced the response to a general anesthetic that could partly be attributed to a loss of neurons in the EC and PC.

Seizures induced by GABAB-receptor blockade in early-life induced long-term GABA(B) receptor hypofunction and kindling facilitation.

Consequences of seizures in the developing brain are not completely understood. The aim of this study was to investigate the long-term alterations of synaptic transmission and seizure susceptibility in the hippocampus after early-life seizures induced by systemic injection of a GABA(B)-receptor antagonist CGP56999A in immature rats. Experimental rats were injected with CGP56999A 1-1.5mg/kg intraperitoneally (i.p.) on postnatal day 15, while controls were injected with saline i.p. Seizures induced by CGP56999A originated mostly from the hippocampus and amygdala, and were associated with no mortality. Thirty days after seizures, laminar field potentials were recorded in the hippocampus in urethane-anesthetized rats by 16-channel silicon probes and analyzed as current source density. As compared to early-life saline-injected rats, early-life CGP56999A-induced seizure rats showed a significant decrease in paired-pulse inhibition of population spikes at 150-400 ms interpulse intervals (IPIs) in CA1, following CA3 stimulation, and at 400 ms IPI in the dentate gyrus, following medial perforant path stimulation. In a separate experiment, adolescent rats that experienced CGP56999A-induced early-life seizures showed a robust facilitation of hippocampal kindling, as compared to saline controls. In conclusion, seizures induced by GABA(B)-receptor blockade in immature rats resulted in a long-lasting loss of GABA(B)-receptor mediated paired-pulse inhibition in CA1 and dentate gyrus, which may contribute to the increase of seizure susceptibility in the hippocampus.

A gliotoxin model of occipital seizures in rats.

PURPOSE: Intracortical microinjection of fluorocitrate, a reversible inhibitor of glial tricarboxylic acid (TCA), results in impaired glial metabolism and epileptic seizures. To determine the potential contribution of epileptic activities to the metabolic properties of fluorocitrate, we investigated the seizure-inducing property of fluorocitrate at different doses. METHODS: Twenty-seven male Sprague Dawley rats (250-400g) were studied with chronically implanted electrodes and cannulae in the occipital cortices. A week after surgery, awake behaving rats were injected with 0.2microl solution containing various concentrations of fluorocitrate or saline in the right occipital cortex; two sham-treated animals did not receive an injection. EEG was recorded with implanted electrodes. Thionin staining was used to verify injection sites. Twenty rats underwent immunohistochemistry for glial fibrilary acidic protein (GFAP) and neuronal nuclear-specific antigen (NeuN) 48h after the injections. RESULTS: Seizures developed within an hour of injection in all the rats that received > or =0.8nmol fluorocitrate and 2 of 4 rats that received 0.4nmol fluorocitrate. Five of 12 animals that received > or =1.2nmol fluorocitrate experienced status epilepticus. There was a significant increase in GFAP staining at the injection site in doses > or =0.8nmol fluorocitrate. There was only mild neuronal loss revealed by NeuN staining at the injection site in the animals that had received 1.6nmol flourocitrate. CONCLUSION: This study shows that fluorocitrate results in focal epileptic seizures with secondary generalization in a dose-dependent manner, including low doses of this agent previously used for studies of brain metabolism.

GABAB receptor blockade enhances theta and gamma rhythms in the hippocampus of behaving rats.

The participation of GABA(B) receptors in hippocampal EEG generation was studied by intracerebroventricular (icv) and intracerebral infusions of GABA(B) receptor antagonist p-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid (CGP35348) in freely behaving rats. During awake-immobility, icv CGP35348 induced a theta rhythm and increased gamma waves (30-100 Hz) in the hippocampus. The immobility theta peaked at 6-7 Hz and had a theta phase in CA1 stratum radiatum of approximately 160 degrees with reference to the theta at the alveus, when compared with approximately 130 degrees during walking. Immobility theta power peaks at 6-7 Hz was also found in normal rats, and it was detected in 27% of the EEG segments during immobility. Incidence of immobility theta increased to 87.5% after 480 nmol of CGP35348 icv. Muscarinic antagonist scopolamine (5 mg/kg, ip) suppressed the induction of immobility theta and the gamma power increase after icv CGP35348. CGP35348 icv did not significantly change the hippocampal theta power at 7-8 Hz during walking (theta fundamental), but it increased power at 12-15 Hz, at the second harmonic of theta. CGP35348 icv also increased 30-50 Hz gamma power during walking. Medial septal infusion of CGP35348 (12 nmol in 0.4 microl) increased the power and the frequency of the hippocampal theta second harmonic during walking, but did not increase gamma activity. Infusion of CGP35348 (8 nmol in 0.4 microl) in the hippocampus increased the local gamma activity at 30-100 Hz, but did not induce immobility theta or affect the walking theta rhythm. In conclusion, icv GABA(B) receptor blockade increased an atropine-sensitive input that generated an immobility theta rhythm, while GABA(B) receptor blockade of the medial septum increased atropine-resistant theta harmonics possibly generated by apical dendritic spikes. GABA(B) receptor blockade may enhance cognitive task performance by activating hippocampal theta and gamma rhythms in behaving rats.

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.

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.

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.

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.

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.

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.

The septohippocampal system participates in general anesthesia.

How the brain mediates general anesthesia is not known. We report that two interconnected structures in the forebrain, the medial septum and the hippocampus, participate in maintaining awareness and movements during general anesthesia. In the awake, freely behaving rat, inactivation of the medial septum or the hippocampus by local injection of a GABA(A) receptor agonist, muscimol, decreased the dose of a general anesthetic needed to induce a loss of the tail-pinch response or a loss of righting reflex. Septohippocampal inactivation also suppressed the behavioral hyperactivity or the delirium stage associated with general anesthesia. An increase and decrease of 30-50 Hz (gamma) waves in the hippocampus correlated with an increase and decrease in behavioral activity, respectively. Similar results were found for both volatile (halothane and isoflurane) and nonvolatile (propofol and pentobarbital) anesthetics. We conclude that the behavioral hyperactivity induced by a general anesthetic is mediated in part by the septohippocampal system, and that depression of the septohippocampal system increases the potency of a general anesthetic. It is suggested that more potent general anesthetics or adjuvants may be developed by maximizing the pharmacological depression of the septohippocampal system.