V. La Grutta

m-Chlorophenylpiperazine excites non-dopaminergic neurons in the rat substantia nigra and ventral tegmental area by activating serotonin-2C receptors.

In vivo electrophysiological techniques were used to study the effect of m-chlorophenylpiperazine, a non-selective serotonin-2C receptor agonist, on the activity of non-dopaminergic neurons in the substantia nigra pars reticulata and the ventral tegmental area of anesthetized rats. Intravenous administration of m-chlorophenylpiperazine (5-320 microg/kg) caused a dose-dependent increase in the basal firing rate of a subpopulation of nigral neurons which do not respond to a footpinch stimulus [P(0) neurons], whereas it did not affect the activity of neurons which are responsive to the footpinch [P(+) neurons]. However, m-chlorophenylpiperazine (5-320 microg/kg) excited all non-dopaminergic neurons sampled in the ventral tegmental area. Moreover, microiontophoretic application of m-chlorophenylpiperazine (10-40 nA) caused an excitation of P(0) nigral and ventral tegmental area neurons. Pretreatment with the selective serotonin-2C receptor antagonist SB 242084 (200 microg/kg, i.v.) completely blocked the excitatory effect of i.v. m-chlorophenylpiperazine (5-320 microg/kg), both in the substantia nigra pars reticulata and in the ventral tegmental area. It is concluded that stimulation of serotonin-2C receptors by m-chlorophenylpiperazine activates non-dopaminergic (presumably GABA-containing) neurons in the substantia nigra pars reticulata and ventral tegmental area.

Inhibitory control by substantia nigra of generalized epilepsy in the cat

Previous investigations have shown that the basal ganglia may exert a regulating influence on cortical epilepsy. Stimulation of the caudate nucleus enhances cortical penicillin (PCN) spikes. Stimulation of globus pallidus internus reduces cortical spike frequency. Since the substantia nigra pars reticulata (SNpr) seems to have an inhibitory action on the ventro-anterior (VA) and ventro-lateral (VL) thalamic nuclei and thalamic neurones send an excitatory influence to the cortex, we undertook an investigation to study nigral influence on cortical epilepsy induced by PCN. Experiments were conducted on encéphale isolé cats in which steady interictal activity was induced by means of parenteral PCN administration (feline generalized PCN epilepsy). Variations occurring in cortical PCN spikes following activation of either pars compacta (SNpc) or SNpr were analyzed. Electrical stimulation of SNpc reduced spike frequency and amplitude in 19% of the total number of stimulations; SNpr stimulation significantly inhibited cortical spikes, especially in the precruciate gyrus, in 80% of cases. The experimental findings constitute an electrophysiological feature of the control exerted by SNpr on the thalamo-cortical re-exciting loop. A putative preferential role of SNpr in the regulation of abnormal phenomena involving the neocortex is emphasized.

The importance of the caudate nucleus in the control of convulsive activity in the amygdaloid complex and the temporal cortex of the cat

Abstract In cats in acute preparation and in cats with chronically implanted electrodes, an investigation was carried out of the effects of caudate nucleus stimulation on intrastimulatory (ID) and post-stimulatory (AD) focal paroxysmal activity in the amygdala and in the temporal cortex. 1. 1. The ID of the ventro-basal complex of the amygdala is greatly reduced by activation of the ipsilateral caudate. When the ID does not exceed 250 μV it is generally totally suppressed. Also the ID of the temporal cortex is inhibited by conditioning stimulation of the caudate-nucleus. 2. 2. The convulsive AD, both in the ventro-basal complex of the amygdala and in the temporal cortex, is suppressed by caudate nucleus stimulation. The optimal parameters of stimulation were studied. 3. 3. Inhibitory effects are present only when conditioning stimulation of the caudate nucleus immediately precedes the test stimulus capable of eliciting the amygdaloid or temporal AD. When caudate nucleus activation follows amygdaloid activation, there is an increase in convulsive activity. 4. 4. In animals with chronically implanted electrodes effective stimulation of the amygdala elicits behavioural phenomena comparable with those of psychomotor epilepsy in man. Conditioning stimulation of the caudate nucleus reduces the animal to a state of immobility without any epileptic manifestations. 5. 5. The potentials elicited in the amygdala and the temporal cortex are inhibited by short duration, high frequency conditioning stimulation of the ipsilateral caudate nucleus. 6. 6. The effects of the inhibitory activity of the caudate nucleus on focal paroxysmal phenomena in the limbic system are discussed.

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.

Relationship between the striatal system and amygdaloid paroxysmal activity.

Abstract To study the anatomic pathways through which neostriatal efferent fibers may influence paroxysmal activity focalized in the amygdala, an experiment was carried out both in acute and in chronic cats. Conditioning stimulation of the globus pallidus and substantia nigra greatly reduced the duration of the afterdischarge (AD) or totally blocked the appearance of the seizure, depending on the stimulus parameters. Caudate conditioning stimulation, conducted with the same parameters as nigral or pallidal activation, was less effective in the control of the AD. Chemical lesion of entopeduncular neurons by means of kainic acid injection, resulted in a decrease of about 50% of the inhibition induced by the caudate nucleus on the amygdaloid AD, whereas kainic acid lesion of the substantia nigra resulted in the disappearance of the caudate inhibition. The essential role of the substantia nigra in the final control of amygdaloid paroxysmal activity is thus emphasized.

Effects of caudate nucleus on paroxysmal activity in hippocampus of cat

Electrically induced afterdischarges (ADs) were evoked in cats dorsal hippocampus. The effect of the conditioning prestimulation of the caudate head on AD duration was tested. A strong inhibitory action was observed when conditioning caudate stimulation immediately preceded hippocampal test stimulation. An increase in threshold values following caudate stimulation was also noted. The time course of the inhibitory phenomenon showed a decrease of the caudate conditioning effect when the interval between the two stimuli increased: complete disappearance of such effect was found to occur at about 600 msec. When caudate head stimulation followed the onset of hippocampal AD, this was inhibited only during caudate stimulation while presenting facilitation after caudate stimulation terminated. The results are discussed in terms of a possible explanation of the contrasting action of the pallidum, while previous findings attesting the facilitatory role of these structures are considered, as are the effects of caudate stimulation on hippocampal AD.

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.

Contrasting effects of centrifugal olivo-cochlear inhibition and of middle ear muscle contraction on the response characteristics of the cat's auditory nerve

Summary The auditory nerve response to clicks over 40 dB range from threshold was recorded in cats with middle ear muscles cut and Flaxedil paralysis. Response characteristics were expressed by intensity functions and by latency-voltage scatter diagrams of the N1 potential. Stereotaxic activation of the crossed olivo-cochlear bundle (OCB) inhibited N1 and produced a unique transformation of its latency-voltage characteristic (Figs. 2, 3). The effect was proportional to the potency of OCB activation. The effect was not seen when the N1 response was reduced by middle ear muscle contraction, the latter affecting the response characteristics in similar manner to that of a simple attenuation of the sound intensity outside the head. The N1 potential represents the modal activity of high CF auditory units from the basal turn of the cochlea, and the above effects on latency characteristics are of teh right order of magnitude to exert a profound influence on binaural interactions at higher order neurons. The membrane mechanism involved in the OCB effect at the inner ear is briefly discussed.

Lateral habenula and hippocampus : a complex interaction raphe cells-mediated

SummaryThe study has shown an excitatory influence exerted by lateral habenula (LH) on hippocampal pyramidal cells. The modulatory influence is paradoxically serotonine-mediated; in fact all LH stimulation effects were abolished by intrahippocampal iontophoretic methysergide application. The data suggest the involvement of dorsal raphe nucleus. In fact, the dorsal raphe nucleus stimulation caused on hippocampus an expected inhibitory effect antagonized by intrahippocampal iontophoretic methysergide application. In the context of this neural structure we have highlighted a disinhibitory relation between two types of cells: slow serotonergic efferent neurones and fast GABAergic interneurones. The disinhibitory hypothesis is also supported by the following experimental tests performed on both slow and fast raphe cells: a) LH stimulation at low and high frequencies; b) iontophoretic administration of NMDA and GABA; c) LH stimulation during intraraphe iontophoretic injection of 2-APV (NMDA antagonist) and bicuculline (GABA antagonist).