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M H Bassant

Publications and source records attributed to M H Bassant.

At least 37 records · Page 2Linked to original sources

Regional distribution of 3-O-methyl-DOPA in the cortex and subcortical structures in the rat: effect of aging.

Dihydroxyphenylalanine (DOPA) and its metabolite 3-O-methyl-DOPA (3-OMDOPA) have been identified as normal constituents in blood, CSF and brain in human and several animal species. In the present study, we report results of 3-OMDOPA measurements in seven cortical areas, hippocampus and striatum of young (3-month-old), middle aged (10-month-old) and aged (27-month-old) rats. 3-OMDOPA was identified in all the areas considered. Regional differences were observed, with the highest levels being found in the hippocampus and the somatomotor and pyriform cortex. A marked increase in the level of 3-OMDOPA was observed in all the cortical areas and in the hippocampus of aged rats. In contrast, this level remained unchanged in the striatum. These modifications were compared to those observed in the levels of dopamine (DA) in the same areas.

Aging↗

Effects of acetylcholine on single cortical somatosensory neurons in the unanesthetized rat.

Experiments have been performed on unanesthetized rats using a chronic restraint system. The animal's head was held in a stereotaxic apparatus by means of two metallic tubes fixed on the skull with dental cement. Electrodes consisted of a recording micropipette (filled with 1 M NaCl and 2% Pontamine Blue) attached to a multibarreled micropipette for iontophoresis. Electrode penetrations were reconstructed on camera lucida drawings of frontal brain sections. The overall percentage of spontaneously active somatosensory neurons was 77% with a mean spontaneous activity of 5.9 impulse/s (n = 405). Yet differences were observed in the proportions of active cells as well as in the mean spontaneous activity between cortical layers (both parameters being significantly higher in layers V and VI). Comparison with results obtained under urethane anesthesia [Dykes R. W. and Lamour Y. (1988) J. Neurophysiol. 60, 703-724] shows that the percentage of the spontaneously active neurons and the mean spontaneous activity were both significantly higher in unanesthetized rats (77 vs 36%; 5.9 vs 2.6 impulse/s). Nevertheless, the laminar distribution of the most active cells was similar under both conditions. In the present study, 52.3% of the neurons (n = 380) were excited by acetylcholine and 46% (n = 198) by carbachol. Significantly larger percentages of neurons excited by acetylcholine were found in layers Vb and VIb. These effects of cholinergic agonists--observed for the first time in unanesthetized rats--differed significantly from those previously obtained under anesthesia (33 and 34% of neurons excited by acetylcholine and carbachol, respectively) [Lamour Y. et al. (1982) Neuroscience 7, 1483-1494].(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Effects of iontophoretically applied monoamines on somatosensory cortical neurons of unanesthetized rats.

The response of somatosensory cortical neurons to iontophoretic applications of monoamines was studied in unanesthetized rats. The animal's head was held in a stereotaxic apparatus by means of a painless head-restraining system implanted 8 days prior to the recording sessions. The electrodes consisted of a recording micropipette attached to a multibarreled iontophoresis micropipette. The electrode penetrations were reconstructed on camera lucida drawings of frontal brain sections. The percentage of cortical neurons responding to application of monoamines were 76% after noradrenaline, 58% after dopamine and 66% after serotonin. The differences observed among percentages of responses seemingly correlate with the relative abundance of terminal axons and receptors for each of the three monoamines in the somatosensory cortex. The vast majority of the responding neurons were inhibited by monoamines and this inhibitory effect was independent of the level of spontaneous activity. The depressant effect of the monoamines on glutamate and acetylcholine-evoked responses supports a modulatory role for these substances. Serotonin was the most potent, followed by noradrenaline and dopamine. The present study shows that when the influence of anesthesia is eliminated, the predominant effect of monoamines on cortical first somatosensory neurons is one of inhibition. These findings contrast with results obtained under some anesthetic conditions, as well as under in vitro conditions.

Acetylcholine↗

Electrophysiological models for the study of cognition enhancers.

Electrophysiological approaches range from global EEG studies to single unit recordings. Quantified EEG studies indicate that cognition enhancers increase the power of fast-frequency (beta) EEG activity in humans and the duration of hippocampal theta in animals. A problem here is the distinction between improved cognition and increases in general arousal, although the two might have the same end effect. A second global approach is the use of the evoked potential or even the conditioned evoked potential, for example the P 300 wave. This approach, using defined brain circuits, would appear to be more specific than global EEG models. Both approaches can be used in parallel studies in animals and man. Studies at more cellular levels can only be used in animals and suffer from severe constraints. The most precise approach, single cell recording, cannot be conducted in freely behaving animals, whereas multi-unit approaches in awake animals tend to produce many artefacts. However, techniques using microintophoretically applied drugs in freely moving rodents and monkeys can contribute to the understanding of mechanisms of action. In vitro studies, for example long-term potentiation in hippocampal slices, may represent a neuronal model of learning but its role in normal brain function has still not been elucidated.

Animals↗

Hemicholinium-3 selectively alters the rhythmically bursting activity of septo-hippocampal neurons in the rat.

The medial septal area contains neurons which project to the hippocampal formation. A sizeable proportion of these septo-hippocampal neurons (SHNs) are cholinergic. About 40% of them also display a characteristic discharge pattern in rhythmic bursts. We hypothesized that SHNs with a rhythmically bursting activity (RBA) are the cholinergic ones. To test this hypothesis we studied the effects of acetylcholine synthesis blockade by hemicholinium-3 (HC-3) on the properties of the SHNs. HC-3 (16, 32 or 64 micrograms total dose) or saline were injected in the lateral ventricles of adult male Sprague-Dawley rats anesthetized with urethane. Extracellular recordings from SHNs in the medial septal area were obtained within hours after HC-3 injections (n = 24 animals). SHNs were identified by their antidromic response following electrical stimulation of the fimbria-fornix. The pharmacological properties of SHNs were studied in some animals using microiontophoretic applications from multibarreled electrodes filled with various neurotransmitters. The hippocampal rhythmic slow activity (RSA or theta) was abolished even after the lowest dose of HC-3 tested (16 micrograms). No significant change in SHNs conduction velocity or spontaneous activity was observed at any dose of HC-3. The percentage of SHNs with RBA was unchanged. In contrast the mean frequency of the RBA was decreased by HC-3 in a dose-dependent fashion. The mean frequency was lowest within the first 3 h after injection. Although the mean spontaneous activity was unchanged SHNs tended to have more spikes per burst. The effects of various neurotransmitters on SHNs were qualitatively unchanged after HC-3 injection. These results suggest that acetylcholine synthesis blockade by HC-3 leads not only to the disappearance of the hippocampal RSA in urethane-anesthetized animals, but also to a decrease in the frequency of the rhythmically bursting activity of the SHNs. Since the 4-Hz hippocampal theta is atropine-sensitive, the results provide indirect evidence that the SHNs with rhythmically bursting activity are the cholinergic SHNs.

Action Potentials↗

Electrophysiological and pharmacological properties of neurons within solid basal forebrain transplants in the rat brain.

Electrophysiological and pharmacological properties of neurons within solid basal forebrain transplants were studied in adult rats anesthetized with urethane. No specific topography of the neurons recorded was observed within the graft. The mean spontaneous activity of the grafted neurons (GNs) was relatively low (4.9 impulses/s) but not unlike that of other central neurons in situ. A large proportion of GNs fired with regular discharges, but other modes of discharge were also observed. A few rhythmically bursting GNs were recorded having a discharge pattern very much like that of the rhythmically bursting medial septal neurons. The responses of GNs to glutamate, gamma-aminobutyric acid, acetylcholine, serotonin and norepinephrine was fairly similar to those described in other central structures.

Acetylcholine↗

Contrasting properties of medial septal neurons projecting to hippocampus or interpeduncular nucleus in the rat.

The properties of neurons of the medial septal nucleus and of the nucleus of the diagonal band of Broca which project to hippocampus or to interpeduncular nucleus were compared in rats anesthetized with urethane. Neurons projecting to the interpeduncular nucleus had a slower conduction velocity and a lower spontaneous discharge rate. In contrast, their responses to various putative neurotransmitters (glutamate, GABA, acetylcholine) were similar. In a few cases, neurons projecting to both structures (i.e., with branched axons) were observed. Both septohippocampal and septointerpeduncular pathways are known to be partly cholinergic. Our results show that they originate from two independent populations of medial septal-nucleus of the diagonal band of Broca neurons with different physiologic properties.

Animals↗

Effect of psychotropic drugs on identified septohippocampal neurons.

The effects of various psychotropic drugs (benzodiazepines, antidepressants, neuroleptics and nootropic drugs, a family of cognition activator agents) on firing rates of septohippocampal neurons, identified by electrical antidromic stimulation, were studied in the medial septum-nucleus of the diagonal band of Broca of rats anaesthetized with urethan. Extracellular potentials from single septohippocampal neurons were recorded using glass pipettes. Drugs were applied by either microiontophoresis or intravenous injections (i.v.). Benzodiazepines produced a marked depression of spontaneous firing rates of septohippocampal neurons whether applied i.v. (diazepam) or iontophoretically (flurazepam, midazolam). In addition, diazepam had a potent depressant effect on the rhythmically bursting activity of the septohippocampal neurons. Baclofen also had an inhibitory effect. Antidepressant drugs (applied by iontophoresis) as well as amphetamine, had a depressant effect on spontaneous firing rates. Neuroleptics (i.v.) had less significant or consistent effects on septohippocampal neurons, although the effects of haloperidol were usually inhibitory. Nootropic drugs were generally ineffective. These data indicate that most psychotropic drugs tested (with the exception of nootropic drugs) have an inhibitory effect on the spontaneous activity of septohippocampal neurons. However, benzodiazepines seem to be more active than antidepressants or neuroleptics. Oxotremorine (i.v.) had a potent excitatory effect on septohippocampal neurons. Atropine (i.v.) increased the septohippocampal neurons' firing rate in some cases. These results are discussed in view of the possible implication of the involvement of septohippocampal neurons in the mediation of the effects of psychotropic drugs on the central nervous system and, more specifically, on the cholinergic systems.

Animals↗

Impairment of the cortical and thalamic electrical activity in scrapie-infected rats.

Cortical and thalamic EEG and somatosensory evoked potential (SEP) induced by stimulation of the somesthetic radiations were studied in scrapie-infected rats. Animals were inoculated intracerebrally with a rat-adapted strain (originating in the C506 M3 mouse scrapie strain). EEG and SEP were recorded from 9 to 17 months after inoculation (ti). Abnormalities (paroxysmal bursts, isolated spikes) first occurred in the cortex (parietal areas) and later in the thalamus, where they were usually less marked. Latencies of the postsynaptic components of the SEP increased at ti + 9 months. This effect became progressively more pronounced and at ti + 15 months, latencies of presynaptic components were also delayed. Nevertheless, marked alteration of the SEP occurred only at the terminal stage of the disease. These findings show that the scrapie-induced disturbances affect more especially the cortex. Decrease of inhibitory processes as well as electronic coupling between cells, resulting from the virus-induced membrane fusion, could produce paroxysmal activity of EEG and SEP impairments.

Animals↗

Spread of scrapie agent to the central nervous system: study of a rat model.

Invasion of scrapie agent into the central nervous system (CNS) was studied in rats following intracerebral and peripheral inoculation, the latter by injection into intact or transected sciatic nerve. Comparison of sleep-wakefulness alterations, neuropathological features, and time lag of electroencephalographic and clinical signs in the 3 groups suggests that hematogenous spread of infection to the CNS may predominate over neural transport, and that peripheral inoculation may closely approximate natural infection.

Animals↗

Changes in the serotonergic, noradrenergic and dopaminergic levels in the brain of scrapie-infected rats.

Levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylethyleneglycol (DHPG) were determined by high-performance liquid chromatography in different brain areas of scrapie-infected rats, 8.5 months after intracerebral inoculation of a rat-adapted strain from mice brain (C 506). At this time, rats developed early clinical signs of the disease. Scrapie-infected rats showed a reduction in the levels of 5-HT and 5-HIAA (frontal cortex, hippocampus, mesolimbic structure). Concentrations of DHPG decreased in the frontal and parietal cortices but remained unchanged in the hippocampus. DOPAC levels decreased in the striatum but not in the mesolimbic structure. These results confirm that the serotonergic, noradrenergic and dopaminergic systems are altered in the brain of scrapie-infected rats. They can partly account for clinical signs of scrapie and are in agreement with the scarce data provided by the postmortem analysis of Creutzfeldt-Jakob disease brains.

3,4-Dihydroxyphenylacetic Acid↗

Monoamine abnormalities in the brain of scrapie-infected rats.

The effects of the scrapie agent on the levels of monoamines and their metabolites, and on choline acetyltransferase (CAT) activity have been investigated in discrete brain areas in the rat. Two strains of scrapie (8745 from sheep brain and C506 M3 from mice brain) were inoculated. Scrapie-infected rats showed a reduction in the levels of serotonin (prefrontal cortex, hippocampus, striatum) and dopamine (striatum) and an elevation of 5-HIAA levels (cerebral cortex, striatum, thalamus). Noradrenaline levels were decreased only in the cerebral cortex and cerebellum of rats infected with the scrapie strain C506 M3. CAT activity remained unchanged. These data suggest that the scrapie agent causes a derangement of noradrenergic, serotonergic and dopaminergic systems in the rat brain.

Animals↗

Experimental scrapie in rats: first electrophysiological observations.

Scrapie was transmitted (1st passage) to various strains of rats through intracerebral (IC) inoculation of sheep-scrapie, mouse-scrapie and hamster-scrapie brains. For the 2nd passage, Wistar rats were chosen and inoculated IC with rat-scrapie brain from the 1st passage. Three groups of 12 rats were considered (S for sheep, M for mouse, H for hamster). Electrodes were chronically implanted for EEG recording. From 100 to 110 days after inoculation, EEG abnormalities were observed, consisting of spindle-shaped bursts of diphasic spikes sporadically occurring during quiet wakefulness. Between 130 and 230 days, EEG signs diversified and became more pronounced. Simultaneously, changes occurred in the sleep-wakefulness cycle: active wakefulness decreased and was replaced by quiet wakefulness (rats were motionless , as if prostrate ). Slow wave sleep diminished, giving way to an unstable low voltage sleep. EEG disturbances clearly preceded the onset of the clinical signs (the latter appearing at about the 8th month). The disease was fairly similar in the S, M and H groups. The interest of the experimental scrapie rat model is discussed in the framework of current research on the neurophysiology of the subacute spongiform encephalopathies.

Animals↗

[Statistical analysis of the activity of pyramidal cells in the dorsal hippocampus of the rabbit].

The spontaneous activity of CA1 pyramidal cells was reduced with microelectrodes from the hippocampus of curarized adult rabbits under painless fixation. A statistical analysis of the data was made by a computer, using a program developed to process time interval series. 1. Various temporal patterns of discharge were observed. A classification into 5 distinct patterns could be disclosed, based on statistical parameters, particularly expectation density, joint interval histogram and interspike interval histogram. 2. The recorded neurones were distributed unequally in these groups, the distribution varying with sleep and wakefulness. 3. Some firing patterns prevailed during wakefulness and some during sleep, but all of them were observed in both states and no one was considered specific to one state. 4. The variability in neuronal discharge was estimated. "Stable" cells (60%) exhibited only one firing pattern. "Unstable" cells (40%) exhibited either two (82%) or three (18%) types of firing. 5. 65% of the cells recorded during waking and then during sleep shifted their firing pattern. The majority of the other units (35%), which kept the same pattern of discharge, were already stable during waking. Hence, they exhibited only one firing pattern and did not appear to be affected by sleep or waking.

Action Potentials↗