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Biomedical subjects

M Sabatino

Publications and source records attributed to M Sabatino.

At least 19 recordsLinked to original sources

Evidence of a contralateral motor influence on reciprocal inhibition in man.

The role of contralateral movement on both H reflex and reciprocal inhibition was studied. In normal men H reflex was induced by median nerve stimulation. Reciprocal inhibition was achieved through stimulation of the antagonist radial nerve. On this basis the effects of contralateral arm movement were analyzed. Furthermore the putative influence of exteroceptive origin was also verified by means of digit stimulation. Results showed that contralateral arm movement did not affect H reflex amplitude; on the contrary, it was able to enhance reciprocal inhibition induced by extensors on flexors. Study of cutaneous afferents demonstrated that contralateral digit stimulation failed to elicit modifications on both H reflex and reciprocal inhibition. On the other hand, ipsilateral digit stimulation lowered H reflex amplitude and increased the degree of reciprocal inhibition. Experimental findings underline the possibility that an informational array reaches the contralateral IA interneuron: therefore a mutual (bilateral) interaction among IA interneurones may accordingly be hypothesised.

Adolescent

Accumbens-caudate-septal circuit as a system for hippocampal regulation: involvement of a GABAergic neurotransmission.

Hippocampal-based epileptiform activity may reach the basal ganglia via the nucleus accumbens. Previous data suggested that caudate nucleus is able to influence hippocampal epilepsy, probably sending a projection to the septum. In order to test the hypothesis of a retrograde activation of accumbens-caudate pathway in hippocampal regulation, we electrically stimulated both caudate nucleus and nucleus accumbens and studied modifications of hippocampal EEG in the feline focal epilepsy model. We also performed bilateral electrolytic lesion of nucleus accumbens and repeated caudate stimulation. Results showed that nucleus accumbens stimulation was ineffective in modifying hippocampal epilepsy; on the contrary, caudate stimulation caused a statistically significant decrease of hippocampal spike frequency and amplitude. On the other hand, in accumbens-lesioned animals caudate activation consistently reduced hippocampal epilepsy to a significant degree. As the caudate nucleus influences hippocampal activity and the septum may constitute a relay station of this functional relation, a possibility was tested concerning a GABAergic mediation. To this end, after a stable caudate-induced effect was reached, an intraseptal microinjection of picrotoxin (GABA receptor antagonist) was made and caudate stimulation repeated at the same parameters. Such a study showed that after intraseptal picrotoxin, caudate stimulation failed to elicit any type of modification of hippocampal activity. Experimental findings support the notion that the striatal modulation on hippocampus is mediated by an anterograde rather than a retrograde pathway, and underline the possibility of a GABAergic caudate-septal influence.

Animals

Dopaminergic control of feline hippocampal epilepsy: a nigro hippocampal pathway.

Substantia nigra is a mesencephalic structure inserted along several circuits which appear to play a key role in epilepsy. In previous researches we postulated that substantia nigra pars compacta (SNpc) may be the site of a precise control of hippocampal epilepsy while substantia nigra pars reticulata (SNpr) may exert a modulation of both neocortical epilepsy and spreading of hyperactivity toward a motor target. In order to better understand mechanisms subserving nigral action in feline hippocampal epilepsy we electrically stimulated SNpc (dopaminergic), before and after sulpiride (dopamine receptor-antagonist) intravenous injection. Furthermore we compared hippocampal epileptiform activity prior to and after apomorphine (dopamine receptor-agonist) intrahippocampal injection as well as prior to and after SNpc electrolytic destruction. Results showed that SNpc is able to regulate hippocampal epilepsy. This effect is selectively antagonized by sulpiride while apomorphine exerts, synergically with SNpc stimulation, inhibitory effects. On the contrary SNpc lesions induces a significant enhancement of hippocampal epileptiform spikes. Experimental findings suggest that SNpc represents a strategic region for the control of hippocampal excitability and that this regulation appears to be dopaminergic in nature.

Animals

A feature of caudate control of focal hippocampal epilepsy: evidence for an anterograde pathway.

Previous experimental evidences showed that the caudate nucleus has a modulatory effect on hippocampal epilepsy. The caudate's regulating action might reach the hippocampus either via the septal region or, retrogradely, via the accumbens nucleus. In order to obtain new data about the pathway involved in caudate hippocampal influence the spreading of abnormal activity towards the nucleus accumbens was studied. Furthermore the effects of caudate stimulation in animals with electrolytic lesions of the nucleus accumbens were analyzed. It was observed that abnormal penicillin-induced activity spreaded from the hippocampus to the nucleus accumbens in about 30 minutes. In animals with and without lesions of nucleus accumbens, caudate stimulation brought about a significant decrease in the frequency and amplitude of hippocampal activity. The results suggest that the nucleus accumbens is reached by the spreading of hippocampal epilepsy but does not participate in the control exerted by the caudate nucleus on the hippocampus. Thus the caudate-induced inhibition takes place through an anterograde caudate-hippocampal circuit, while at the same time excluding retrograde activation by way of a caudate-accumbens-hippocampal pathway.

Animals

Relay stations and neurotransmitters between the pallidal region and the hippocampus.

The effects of internal pallidum and lateral habenula stimulation on epileptiform activity of cat's hippocampus were studied. A steady interictal activity was induced by locally applied sodium penicillin (PCN) solution. Both pallidal and habenular electrical stimulation caused an increase in spike frequency and amplitude. Intraperitoneally injected atropine sulphate failed to modify pallidal and habenular influences. Intraperitoneal methysergide bimaleate (5-HT antagonist) suppressed the effects of habenular stimulation. In contrast to the effects of pallidal and habenular stimulation, raphe electrical stimulation inhibited hippocampal spiking and intra-raphal muscimol (a GABA receptor agonist) enhanced hippocampal-based epilepsy. After muscimol, raphe stimulation at the same threshold parameters failed to affect hippocampal activity. In cats with habenular lesions hippocampal spike frequency and amplitude were reduced and intra-raphal muscimol did not affect the hippocampus. The results are discussed in the light of a complex interrelationship between basal ganglia and hippocampus. The role of the lateral habenula and of the medial raphe as relay stations between the two regions is emphasized.

Action Potentials

Electrophysiological and microiontophoretic analysis of the habenulo-hippocampal circuit.

In the cat, the effects of lateral habenula stimulation, at different ranges of frequency, on hippocampal units were studied. Habenular stimulation at low frequency excited, while at high frequency inhibited the greater part of hippocampal units. Moreover, in order to clarify the possible pathway involved in the habenulo-hippocampal circuit, the effects of iontophoretic acetylcholine and serotonin on hippocampal units were compared with those of habenular stimulation. Iontophoretic acetylcholine induced both excitatory and inhibitory responses while serotonin induced only inhibitory responses. Iontophoretic atropine blocked the effects of acetylcholine ejection but did not antagonize stimulation effects; ion-tophoretic methysergide induced an increase of basal firing of hippocampal units and antagonized both serotonin and habenular stimulation inhibition. The results suggest an influence of lateral habenula to the hippocampus which does not appear to be cholinergically-mediated. A possible involvement of the raphe as a relay station in the habenulo-hippocampal pathway is discussed.

Acetylcholine

Substantia nigra-mediated anticonvulsant action: a possible role of a dopaminergic component.

A number of neural pathways may mediate nigral control of epilepsy. According to the literature, a GABAergic nigrotectal pathway may be responsible for the control exerted by the substantia nigra on the diffusion of discharges toward spinal targets, while the nigrothalamic projection may transfer nigral influence on premotor neocortical epilepsy. Since there is probably an anatomical nigrohippocampal pathway arising from dopaminergic cells in the substantia nigra, we tested the effects of stimulating the substantia nigra pars compacta (SNpc) on focal hippocampal epilepsy induced by penicillin injection in the cat. The possibility of dopamine involvement was further tested by studying the effects of intraperitoneal injection of haloperidol, a dopamine receptor blocking agent on nigrohippocampal influences, while to verify the precise site of action, in other groups of cats, sulpiride and apomorphine (D-receptor antagonist and agonist, respectively) were locally administered in the dorsal hippocampus. Furthermore, modifications of hippocampal epileptiform EEG were studied in control conditions and following SNpc electrolytic lesions. Results showed a strong nigral suppressive effect on focal hippocampal epilepsy. Nigral stimulation induced a significant decrease in both frequency and amplitude of hippocampal spikes, which disappeared either about 10 min after i.p. injection of haloperidol 1 mg/kg or about 5 min after intrahippocampal administration of sulpiride, and did not return during a further hour or more of experimental observation. It should be emphasized that in the absence of nigral stimulation, both haloperidol and sulpiride did not modify hippocampal spike frequency. Apomorphine application to dorsal hippocampus induced a marked reduction of hippocampal epileptiform activity parallel to the effect observed during SNpc stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Nigral influence on focal epilepsy.

The substantia nigra (SN) has been proposed as a structure involved in epileptiform phenomena. Previous investigations demonstrated that SN is able to elicit hippocampal rhythmic slow activity (RSA) as well as to inhibit hippocampal interictal spikes induced by parenteral administration of penicillin. The present series of experiments was carried out in order to characterize the action of SN on a focal model of hippocampal epilepsy. Experiments were performed on encéphale isolé cats in which steady epileptiform activity was induced by locally applied penicillin. Electrical stimulation of SN pars reticulata (pr) caused a statistically significant decrease of hippocampal spike frequency and amplitude in 30% of the total number of stimulation sessions. Stimulation of SN pars compacta (pc) was even more effective. It induced inhibitory effects on hippocampal spikes in 91% of the cases. In 30% of the cats, RSA was noted on hippocampal recordings in correspondence to nigral activation. Experimental data support the hypothesis that the SNpc influences hippocampal excitability: a differential role may be played by SNpc and SNpr in the control of seizure processes.

Animals

Striatonigral suppression of focal hippocampal epilepsy.

Both caudate nucleus (CN) and substantia nigra (SN) appear to be involved in the control of epileptogenic events. Previous investigations had demonstrated that both CN and SN stimulations are able to induce hippocampal theta (theta) rhythm and an inhibition of epileptiform spikes. Since the two structures are reciprocally linked by fibre pathways, experiments were carried out to test the possibility that CN influences the hippocampus via SN or vice versa. To this end, changes in penicillin-induced hippocampal spikes by CN or SN stimulation were studied before and after destruction of SN and CN respectively. Steady interictal activity was induced in the hippocampus of encéphale isolé cats by local injection of penicillin. Stimulations of both CN and SN induced statistically significant reduction of hippocampal spike frequency, and in some cases a clear and regular theta-rhythm. These effects were unchanged by the destruction of either CN or SN. The results add further information to the role played by the basal ganglia and SN in the control of epilepsy, and underline the possibility that caudate and nigral influences on the hippocampus are mediated by different pathways.

Action Potentials

Reinforcement of reciprocal inhibition by contralateral movements in man.

A reduction of flexor carpi radialis H reflex size was produced by submotor threshold stimulation of the radial nerve. This reduction reflects reciprocal inhibition exerted by the inhibitory IA interneuron. The effects of contralateral movements on IA reciprocal inhibition were studied in eight normal subjects. Active contralateral arm movement appeared to significantly increase the degree of reciprocal inhibition without affecting the unconditioned reflex. A minor enhancement of reciprocal inhibition was also noted after passive mobilization. Results are discussed in terms of contralateral segmental afferent fibers influencing IA interneuronal excitability. They strongly suggest that contralateral muscular IA afferents may reinforce reciprocal inhibition in man.

Adult

Focal hippocampal epilepsy: effect of caudate stimulation.

The basal ganglia seem to be involved in the control of abnormal hippocampal activity. The caudate nucleus has been reported to elicit hippocampal theta rhythm and to inhibit epileptiform spikes. Experiments were conducted to test the action of caudate stimulation on focal penicillin epilepsy of the hippocampus in the cat prior to and after septal coagulation and parenteral atropine administration. Results showed that the caudate is able to reduce both hippocampal spike frequency and amplitude. The effects are abolished by septal lesions and either decreased or totally suppressed by atropine administration. The findings are discussed in terms of caudate influence on septum; the importance of cholinergic pathways is also emphasized.

Action Potentials

A study of caudate inhibition on an epileptic focus in the cat hippocampus.

The mechanisms whereby the caudate nucleus modifies hippocampal spiking activity have been studied. Epileptiform activity was induced in the cat hippocampus by topical application of sodium penicillin in different concentrations. The frequency of induced spikes appeared to be directly correlated to the two doses of epileptogenic agent. The inhibitory effect of 10 Hz caudate stimulation on spike frequency was present even when stimulation lasted for 180 s. Likewise 25 Hz caudate stimulation brought about an inhibition which was maintained by stimulus trains lasting up to 90 s, while the degree of inhibition was reduced by trains of longer duration (120, 150 and 180 s); similar results were also noted in some atropine-treated cats. The time course of spikes in cats with electrolytic lesions of the caudate exhibited an increase in both frequency and duration. The results indicate that there is an optimal parameter for caudate stimulation causing inhibition of penicillin-induced hippocampal spiking activity, and suggest the possibility of tonic control of hippocampal excitability exerted by the caudate nucleus.

Animals

An electrophysiological study of habenular influence on hippocampus.

The action of lateral habenula (LH) stimulation on focal epileptiform activity in the hippocampus was studied. Local microinjection of sodium penicillin induced a steady interictal activity in the dorsal hippocampus. Low frequency electrical stimulation of the habenula caused a marked enhancement of spike activity in both frequency and amplitude. The effect was blocked by intraperitoneally injected methysergide. The facilitatory influence of the habenula on hippocampal activity might be due to a disinhibitory mechanism. The results are regarded as suggesting that the habenula may be a relay station between the basal ganglia and the hippocampal formation. LH as well as basal ganglia might modulate hippocampal excitability, exerting a control on the genesis and diffusion of abnormal activities.

Animals

Study of spindle-spike interactions: features of basal ganglia control.

Changes in cortical spindle distribution following penicillin (PCN) injections were studied in feline generalized PCN epilepsy. PCN activation caused no substantial changes in spindle duration, frequency and intraburst frequency, while significant reductions in the amplitude of the negative waves were noted. At the same time combinations of spindle waves and epileptic complexes were recorded with one or more spikes randomly occurring at the beginning, in the middle, or at the end of a spindle envelope. Low frequency stimulation of the caudate nucleus induced a certain degree of enhancement in cortical precruciate spike frequency while high frequency activation of the entopeduncular nucleus caused significant inhibition of cortical spike frequency. The results are discussed in the light of the reciprocal interrelationship between spindles and spikes. Furthermore, the role played by the caudate and the entopeduncular nucleus in the control of the cortico-thalamo-cortical circuit is also emphasized.

Animals

Hippocampal seizures and striatal regulation: a possible functional pathway.

Experimental findings have suggested the possibility of a functional relationship between the basal ganglia and the hippocampus. Previous research has revealed a predominantly inhibitory action of the caudate nucleus (CN) and an excitatory effect of the globus pallidus (GP) on electrically induced hippocampal afterdischarges (HAD). The effects of electrolytic destruction of the CN on the threshold and duration of HAD has been studied in the 'encéphale isolé' cat. The threshold and duration of HAD was also studied following conditioning stimulation of the CN in animals in which the inner segment of the globus pallidus (GPi) and medial septal nucleus (MSN) had been destroyed. Following CN lesions, the hippocampal excitability threshold underwent a significant reduction, while the duration of HAD appeared to be increased. Following destruction of the GPi and MSN, the threshold and duration of HAD exhibited no change following conditioning stimulation of the CN. The results reveal a tonic inhibitory effect of the CN on the hippocampus and suggest that a strio-pallido-septal pathway is the anatomical substrate for the effect.

Animals

Modulation of paroxysmal activity in the hippocampus by caudate stimulation in the chronic cat.

Afterdischarges in the dorsal hippocampus (HADs) were studied in freely-moving cats with implanted electrodes following threshold stimulation of the mirror-image point on the contralateral side. Marked inhibition, similar so that seen in acute animals, was observed when the test stimulation was immediately preceded by a conditioning stimulus applied to the caudate nucleus. The inhibitory effect appeared to be larger in these chronic animals than in the acute preparations previously studied, probably because of the total absence of anaesthesia during the recording session. When the HAD is preceded by caudate stimulation, its duration can be graduated by the intensity of the hippocampal test stimulation. The results are discussed in terms of a possible modulation induced directly or indirectly by the caudate nucleus in the hippocampus, which reacts in a gradual manner to the excitatory volley.

Action Potentials