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Biomedical subjects

P Monmaur

Publications and source records attributed to P Monmaur.

At least 19 recordsLinked to original sources

Effects of Huperzine used as pre-treatment against soman-induced seizures.

Huperzine A (HUP), an alkaloid isolated from the Chinese club moss, Huperzia serrata is a reversible inhibitor of cholinesterases which crosses the blood-brain barrier and shows high specificity for acetylcholinesterase (AChE) and a prolonged biological half-life. We tested, in vivo, its efficiency in protecting cortical AChE from soman inhibition and preventing subsequent seizures. The release of acetylcholine (ACh) was also followed in the cortex of freely moving rats using microdialysis techniques. We previously found that soman-induced seizures occurred in rodents only when the cortical AChE inhibition was over 65% and when the increase of ACh level was over 200 times the baseline level. This was verified in the present study in control animals intoxicated by 1 LD50 of soman (90 microg/kg). Using the same dose of soman in rats pre-treated with 500 microg/kg of HUP, we observed that 93% of the animals survived and none of them had seizures. This dose of HUP reduced AChE inhibition to 54% and increase of ACh level to 230 times baseline value. HUP thus appears as a promising compound to protect subjects against organophosphorus intoxication.

Acetylcholine↗

Acetylcholine release in the hippocampus of the urethane anaesthetised rat positively correlates with both peak theta frequency and relative power in the theta band.

The need to achieve a clearer understanding of relations between hippocampal theta characteristics and cholinergic septohippocampal neuron activity, prompted us to re-examine, in the urethane-anaesthetised rat, the statistical relationships between the electrophysiological and neurochemical variables using a procedure which is believed to enhance significantly the degree of confidence with which parameters of theta recorded with classic macroelectrodes can be related to concomitant acetylcholine output measured by high-performance liquid chromatography with electrochemical detection. Firstly, the theta rhythm and the acetylcholine content were derived from the same hippocampus. Secondly, the hippocampal electroencephalogram was quantified using spectral analysis which permits the more objective quantitative evaluation of selected electroencephalogram samples. Thirdly, a larger number of rats than in our previous study was used here, thus enhancing the validity of statistical results. This procedure yielded, in our time-course determination, two main findings. The first finding is that acetylcholine release was positively correlated with frequency at the peak power of the theta band which reflects the frequency of the theta signal. This finding had not been reported yet. The second finding is that hippocampal acetylcholine outflow also covaried with relative power of the theta band which reflects the amplitude of the theta signal. This finding is consistent with our previous study in which EEG was quantified by means of a traditional method. These findings suggest that the cholinergic component of the septohippocampal system, which is the main source of hippocampal acetylcholine, and neurophysiological mechanisms involved in the modulation of both the amplitude and the frequency of theta are functionally related. The possibility that, at least in the urethane-anaesthetised rat, hippocampal acetylcholine is involved in these modulator mechanisms is discussed.

Acetylcholine↗

Involvement of septal muscarinic receptors in cholinergically mediated changes in rat rearing activity.

We tested the hypothesis that septal muscarinic receptors of the rat are involved in exploratory behavior control, at least as reflected in the measure of rearing activity. At a dose capable of inducing hippocampal theta rhythm, carbachol injection into the septum significantly increased the number of rearings from the 2nd to the 5th min postinjection. The increase was maximal in the 3rd min and gradually declined until the 9th min postinjection, when it was near the control level. This behavioral effect was blocked by prior injection of atropine. These data, when considered with other findings showing a similar motor response caused by the hippocampal injection of the cholinergic agonist, strongly suggest that the cholinoceptive cholinergic components of the septohippocampal system play a role in the release of exploratory behavior. This role might be mediated via muscarinic receptors at the septal level. Moreover, the time course of behavioral action of carbachol injected into the septum is of particular importance for studies on the effect of the drug on performance of the rat in learning and memory tests requiring contribution of exploratory behavior.

Animals↗

Relations between acetylcholine release and electrophysiological characteristics of theta rhythm: a microdialysis study in the urethane-anesthetized rat hippocampus.

In urethane-anesthetized rats, recording electrodes were implanted in the left dorsal hippocampus and a dialysis probe was placed in the contralateral dorsal or ventral hippocampus. Samples of extracellular acetylcholine (ACh) levels were assessed at 10-min intervals over a period of 30 min using microdialysis with high-performance liquid chromatography with electrochemical detection. EEG was recorded during the same period and amplitude, frequency, and duration of theta rhythm were calculated for each of the three 10-min intervals. Data were analyzed using the two-tailed Spearman rank-order correlation test. A positive and high rank correlation coefficient (rho = 0.90, p < 0.01, n = 8) was seen between the average ACh outflow in the dorsal hippocampus and the average theta amplitude, both being calculated for the entire collection period. A lower but statistically significant positive correlation (rho = 0.59, p < 0.01) between dorsal hippocampus ACh output and theta amplitude was also found when the couples of values collected for the 30-min period were pooled (n = 20). In contrast, frequency and duration of theta were not significantly correlated with dorsal hippocampus ACh release. Also, no statistically significant correlation (p > 0.05) was found between ACh output in the ventral hippocampus and theta parameters. Because changes in hippocampal ACh outflow are believed to be the reflection of changes in number and/or level of activity of cholinergic afferents to the dorsal hippocampus, our present findings support the view that, at least in the dorsal hippocampus of the urethane-anesthetized rat, the septohippocampal cholinergic projection regulates the theta amplitude but not frequency. Finally, the possibility that ACh outflow increase and tonic release in the hippocampus is not a sufficient condition to induce and maintain theta in the urethane-anesthetized rat is discussed.

Acetylcholine↗

Intraseptal infusion of selective and competitive glutamate receptor agonist NMDA and antagonist D-2-amino-5-phosphonopentanoic acid spectral implications for the physostigmine-induced hippocampal theta rhythm in urethane-anesthetized rats.

Theta (theta) rhythm may be mediated, at least in part, by a glutamate neurotransmitter. Thus, in the present study, it was hypothesized that the septum glutamatergic NMDA receptor subtype may be involved in the modulation of physostigmine-induced theta rhythm. To test this hypothesis, we analyzed, in the urethane-anesthetized rat, the effects of septum application of NMDA and D-2-amino-5-phosphonopentanoic acid (AP5), selective and competitive NMDA agonist and antagonist, respectively, on the spectral characteristics of hippocampal theta rhythm elicited by intravenous injection of a anticholinesterase agent, physostigmine. A low dose (16 nmol) of AP5 did not significantly affect EEG recordings, whereas a high dose (50.75 nmol) resulted in significant decreases in phase (-61.8%) at theta frequency, peak theta power (-64.2%), and absolute power of the low-frequency theta band (-67%). These electroencephalographic alterations, which appeared at 50.75 nmol AP5, were amplified following application of massive doses of the drug (121.8 nmol, n = 1, and 162 nmol, n = 1). Amplification, however, was slight and the theta waves remained clearly detectable. On the other hand, the infusion of NMDA resulted in a significant increase in frequency (+25%) of this rhythm, but this effect was completely antagonized by prior local administration of 16 nmol AP5. Our data suggest that the septal NMDA receptors exert subtle modulatory influences on the septohippocampal cells involved in physostigmine-induced theta wave production, which has not been reported elsewhere: tonic with respect to both low-frequency theta band power and theta phase, and phasic with respect to theta frequency. Our data also indicate that the septum may be a sensitive action site for exogenously administered glutamatergic drugs.

2-Amino-5-phosphonovalerate↗

Involvement of M2 and non-M2 muscarinic receptors in hippocampal theta rhythm induced by carbachol infusion into the septum of the rat.

Binding and autoradiographic studies have shown the presence of a rather high density of M2 muscarinic subtype receptors and the apparent absence or low density of the M1 subtype in the septum. We tested the hypothesis that, in the urethane-anesthetized rat, septal M2 receptors are involved in the generation of the hippocampal theta (theta) rhythm induced by intraseptal administration of carbachol, a potent cholinomimetic agent. Carbachol-induced theta was blocked by local infusion of the unspecific muscarinic antagonist agent, atropine (20 micrograms (29.55 nM)), given 10 min prior to carbachol. The intraseptal administration of low to high doses of gallamine (range: 20-180 micrograms (22.43-201.90 nM)), a specific M2 antagonist which displays high affinity for the septal region, resulted in significant changes in the electrophysiological characteristics of carbachol-induced theta but failed to abolish this rhythm. It is suggested that the latter may have resulted from a combined activation of both M2 and non-M2 receptors at septal level.

Animals↗

Hippocampal EEG responses induced by carbachol and atropine infusions into the septum and the hippocampus in the urethane-anaesthetized rat.

Infusion of 1 microgram of carbachol, a potent cholinergic agonist, into the lateral septum of the urethane-anaesthetized rat systematically caused the induction of clear-cut hippocampal theta (theta). However, infusion of an equivalent amount of the drug into the hippocampus, close to the recording electrode, failed to induce theta in 50% of the animals and produced a mixture of theta waves and desynchronized activity, resulting in atypical EEG patterns, in the remaining subjects. Both carbachol EEG effects were blocked by intraseptal infusion of the antimuscarinic agent, atropine. Our data demonstrate that muscarinic receptors in the septum are predominant sites for cholinergic agonist-antagonist action capable of generating or suppressing hippocampal theta in the rat. They also indicate that intraseptal cholinergic mechanisms play an important role in the initiation and generation of this rhythm.

Anesthesia↗

Changes in hippocampal acetylcholine and glutamate extracellular levels during soman-induced seizures: influence of septal cholinoceptive cells.

The changes in extracellular acetylcholine and glutamate levels were determined, during the course of seizures induced by soman, an irreversible inhibitor of acetylcholinesterase, in the CA1 hippocampal area of rats previously injected with atropine or normal saline into septum. The marked increases observed in soman-treated animals were abolished in rats receiving atropine. These data strongly suggest that, during soman intoxication, septal cholinoceptive cells play a key role in controlling the release of acetylcholine and glutamate in hippocampus. The mechanisms underlying this phenomenon are discussed.

Acetylcholine↗

Elicitation of hippocampal theta by intraseptal carbachol injection in freely moving rats.

Following infusion into the septum of carbachol, a powerful muscarinic agonist, a theta (theta) rhythm was emitted during complete relaxed immobility as well as during automatic movements. This was not seen following administration of the drug within the caudate/putamen, which is rich in muscarinic receptors but which is not believed to be involved in hippocampal theta generation. Local administration of atropine abolished carbachol-induced theta but did not suppress the theta which normally occurs during voluntary movements. These findings clearly demonstrate that at least a component of the hippocampal theta may be manipulated by intraseptal administration of muscarinic agents, thus supporting our previous assumption that, in theta generation, the septum may be a sensitive site of action for exogenously administered cholinomimetic drugs. They also raise the possibility that the activity of the well identified septohippocampal system involved in the presumed cholinergic hippocampal theta generation is regulated trans-synaptically by acetylcholine at the septal level. Finally, our micropharmacological approach, by suggesting the carbachol-responding septohippocampal cells pacing theta rhythm which is correlated to important functional states, such as attentive waking and active sleep, provides a potential powerful tool for clarifying the neurobiological function of the septohippocampal pathway.

Analysis of Variance↗

Effects of transient cerebral ischemia on the hippocampal dentate theta (theta) profile in the acute rat: a study 4-5 months following recirculation.

This study mainly describes the long-term effects of 20 min of cerebral ischemia on the profile of the presumed cholinergic theta rhythm in the rat dorsal hippocampal formation during ether anesthesia and injection of the muscarinic agonist agent arecoline. The experimental data were collected 4-5 months after ischemia. They show that ischemia results in a statistically significant reduction in both superficial and deep theta recorded from the CA1 area of the hippocampus and the dentate gyrus, respectively. Amplitude reduction is similar for both rhythms and co-varies positively with the extent of CA1 stratum pyramidale damage which, from light microscope observation, appeared to be the major neuroanatomical consequence of ischemic insult in the dorsal hippocampal formation. The medial septal nucleus-diagonal band of Broca complex involved in theta generation did not suffer visible anatomical damage. Moreover, no significant alteration in the spatial distribution and the density of hippocampal dentate acetylcholinesterase reaction product was seen in ischemic animals. These histological data were statistically confirmed by computerized image analysis. Finally, this is the first investigation to show that transient interruption of cerebral blood flow results in a long-lasting alteration of theta rhythm which is probably the major aspect of the basic activity of the hippocampal formation. Thus, the present findings obtained in the acute rat at 4-5 months postischemia confirm and extend, in most respects, our previous results collected in the chronic animal 2-29 days following 4-vessel occlusion. Possible significance of these findings for the hypothesis of the dependent generation sites of superficial and deep thetas in the hippocampus assumed to be crucial in learning and memory, is discussed.

Acetylcholinesterase↗

Effects of unilateral cerebral ischemia on the hippocampal theta depth profile in the ether-anesthetized Mongolian gerbil.

In gerbils (Meriones unguiculatus) unilateral cerebral ischemia of 5 to 15 min resulted in selective destruction of the ipsilateral hippocampal CA1 stratum pyramidale. It also produced an obvious amplitude reduction in both superficial and deep theta rhythms recorded from damaged hippocampal formation. The presence of normal theta in the left normoxic hemisphere showed that the septohippocampal projections, integrity of which is essential for theta appearance, were spared by ischemia. These data have implications in relation to the two generators hypothesis of theta.

Anesthesia↗

Effects of selective lesions of fimbria-fornix on learning set in the rat.

The effects of selective partial lesions of the Fimbria-Fornix (FiFx) on reversal and place learning sets were investigated in rats by using a T-maze and a semi-circular multiple discrimination apparatus. Lesions restricted to the Fimbria (Fi) produced a significant deficit in reversal and place learning set, whereas lesions to the Fornix (Fx) only disturbed the learning set based on a reversal procedure. Combined Fi + Fx lesions resulted in impairment in the retention of spatial discrimination tested in the two mazes. Ventral Hippocampal Commissure (vhc) had no significant effect on reversal learning set. These results confirm previous data that the hippocampal formation is involved in learning transfer, and suggest that the Fi and the Fx may play a role in learning set. Our data also confirm previous demonstrations of the ability of rats to rapidly acquire place learning set.

Animals↗

Temporal changes in hippocampal theta activity following twenty minutes of forebrain ischemia in the chronic rat.

The present study was designed to examine the temporal changes in the theta (theta) rhythm recorded from the dorsal hippocampal formation of the chronic rat following 20 min of cerebral ischemia. Recordings were made during both wakefulness and paradoxical sleep. The experimental results show that ischemia resulted in a drastic amplitude reduction in both superficial and deep theta. Amplitude reduction occurred between days 1 and 4 postischemia and was maintained across the subsequent survival period. This EEG alteration was associated with an excessive loss of pyramidal cells in the hippocampal CA1 area, as observed by light microscopy. The above data strongly support our previous conclusions that neural components of the CA1 area may be of fundamental importance for the appearance and the maintenance of not only superficial theta but also deep theta. Moreover, they suggest that the preparation used in the present study may be a useful model for investigations on the neuroanatomophysiological effects of transient cerebral ischemia.

Animals↗

Spatial distribution of hippocampal-dentate theta rhythm following colchicine injection into the hippocampal formation of the rat.

This investigation confronts the basic question of dentate granule cell participation in the generation of superficial and/or deep theta recorded from the dorsal hippocampal formation in the ether-anesthetized rat. Granular cells were destroyed unilaterally by local injection of 2 micrograms of colchicine (COL) dissolved in 0.2 microliter of distilled water. Hippocampal EEG was recorded 8 days after the neurotoxin injection. The COL injection which destroyed most dentate granular cells but left nearby pyramidal cells of the hippocampal CA1 area virtually unaffected, failed to disrupt significantly either superficial or deep theta. In contrast, the COL injection which destroyed most dentate granular cells and, also, caused some damage to the nearby pyramidal cells of the CA1 area, resulted in a sharp alteration of both theta. These data strongly suggest that granular cells of the dentate gyrus may not be critically involved in theta production, at least in the ether-anesthetized rat. They also confirm a previous conclusion that the neuroanatomical integrity of the CA1 area of the dorsal hippocampus is necessary for the normal appearance and maintenance of both superficial and deep theta. These data are discussed in the context of the generally accepted notion that superficial and deep theta are produced by the rhythmic activity of CA1 pyramidal cells and dentate granular neurons respectively.

Animals↗

Hippocampal-dentate theta disturbance after selective CA1 pyramidal cell damage in the rat.

The contribution of the CA1 area of the dorsal hippocampus to both superficial and deep theta recorded from the dorsal hippocampal formation was assessed in rats anesthetized with ether. CA1 area cells were destroyed unilaterally by local injection of 2 micrograms of ibotenic acid dissolved in 0.1 microliters of phosphate buffer. Limited destruction of CA1 resulted in partial suppression of both superficial and deep theta, whereas extensive destruction resulted in almost total suppression of both theta's. A good correlation was found between the extent of the lesion and the theta disruption. Control preparations involving destructions by means of this neurotoxin of the hippocampal CA3 area or lower blade of the dentate gyrus failed to alter either superficial or deep theta. These data suggest that neuroanatomical integrity of the CA1 area of the dorsal hippocampus is a necessary condition for the normal appearance and maintenance of both superficial and deep theta as recorded from the dorsal hippocampal formation of the ether-anesthetized rat.

Animals↗

Selective lesions of the fimbria and the fornix in the rat: differential effects on CA1 and dentate theta.

The effects of electrolytic lesions of the dorsal fornix and the dorsomedial fimbria on the CA1 and the dentate theta rhythms (theta s) recorded from the dorsal hippocampal formation were investigated in the ether-anesthetized rat. The results showed that (i) fornix lesions mainly affected CA1 theta, (ii) fimbrial lesions mainly affected dentate theta, and (iii) combined fornix-fimbria lesions suppressed both CA1 and dentate theta s. When considered in connection with other observations, these data suggest that the septal projections pacing the CA1 theta may course essentially within the dorsomedial fornix whereas those pacing the dentate theta may pass essentially within the dorsomedial fimbria. Moreover, our data provide new support for the hypothesis that at least two septohippocampal neural systems are anatomically and functionally independent and capable of controlling the theta activity of the dorsal hippocampal formation of the anesthetized rat.

Animals↗

Influence of female odors on lateral hypothalamus in the male rat. Semiquantitative deoxyglucose analysis.

The uptake of 14C deoxyglucose (2DG) has been studied in various hypothalamic and limbic structures of male rats exposed to female odors. Uptake differences were visualized by image processing and quantified by measurement of optical density ratios. With respect to the control group, an increase in uptake was observed in the lateral hypothalamic area (LHA), not only in the olfactory bundle, but also, and more obviously, in the parafornical part. This 2DG response is not a result of an odor-induced general motor activation, although it seems to depend on the behavioral reaction of the animal towards the odor. A similar correspondence was not observed for the 2DG response to odor in the ventromedial hypothalamus. Observations in the medial preoptic area, in the corticomedial amygdala, in the lateral septum, or in the dorsomedial hypothalamus did not reveal any significant change in 2DG uptake.

Animals↗