N. Vella

Striatal and septal influence on hippocampal theta and spikes in the cat

The experiments studied the modulation exerted by the septum and the caudate nucleus on hippocampal activity in the cat. Injections (i.v.) of sodium penicillin were performed in order to obtain a steady interictal epileptic activity. Hippocampal slow rhythmic activity showed a marked decrease either in duration or in frequency following penicillin activation. Both septal and caudate electrical stimulation inhibited spike frequency through a theta eliciting mechanism. Caudate stimulation failed to determine any sort of effect after medial septum lesions. The importance of the septum as modulation station between basal ganglia and hippocampus is emphasized.

Dopaminergic control of feline hippocampal epilepsy: A nigrophippocampal 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.

Effects of substantia nigra and pallidum stimulation on hippocampal interictal activity in the cat

In the present work the role played by substantia nigra pars compacta and globus pallidus pars interna on hippocampal bioelectrical activity is studied. Injections of sodium penicillin (i.v.) produce steady interictal spikes in the hippocampus. Substantia nigra stimulation induces regular theta rhythm and inhibits the spikes. Pallidal stimulation, on the contrary, appears to strongly enhance epileptiform activity, proceeding to generalized seizure activity. The results are discussed in the light of the interrelationships between basal ganglia and hippocampus, hypothesizing a putative feedback loop from striatal to limbic centers.

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.

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

SummaryPrevious experimental evidences showed that the caudate nucleus has a modulatory effect on hippocampal epilepsy. The caudates 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.

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.

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.

Electrophysiological and microiontophoretic anatysis 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.