Organization of efferent projections of the subthalamic nucleus in the squirrel monkey as revealed by retrograde labeling methods

The cellular origin and degree of collateralization of the subthalamostriatal, subthalamonigral and subthalamopallidal projections in the squirrel monkey (Saimiri sciureus) were studied using lectin-conjugated horseradish peroxidase (WGA-HRP), Nuclear yellow (NY) and Fast blue (FB) as retrograde tracers. In a first experimental group, WGA-HRP was injected in the left putamen and the right caudate nucleus. Following these injections numerous retrogradely labeled neurons occurred in the dorsolateral two-thirds of the subthalamic nucleus on the putamen-injected side, whereas a smaller number of positive cells were found in the ventromedial third of the same nucleus on the caudate-injected side. In a second experimental group NY was injected in the putamen whereas FB was delivered in the substantia nigra on the same side of the brain. After putaminonigral injections subthalamic cells containing the tracer injected in the putamen (about 75-80% of all retrogradely labeled neurons) occurred in the dorsolateral two-thirds of the nucleus, whereas those containing the tracer injected in the substantia nigra (about 20-25% of all positive subthalamic cells) were confined to the ventromedial third of the structure. Approximately 5-10% of all subthalamic positive neurons were double-labeled following putaminonigral injections. In a third experimental group, NY was injected in the caudate nucleus and FB in the substantia nigra on the same side. After such injections cells retrogradely labeled with NY or FB were present in about equal number and appeared closely intermingled in the ventromedial third of the subthalamic nucleus. Less than 10% of all positive subthalamic neurons were double-labeled following caudatonigral injections. In a fourth experimental group, NY was delivered in the globus pallidus and FB in the substantia nigra on the same side. In these animal cells containing the tracer delivered in the pallidum were about 4 times more numerous than those labeled with the tracer injected in the substantia nigra, and approximately 10-20% of all positive subthalamic neurons were double-labeled following pallidonigral injections. Most of these double-labeled cells occurred in the zone where the two populations of single-labeled cells overlapped. Finally, in a last experimental group, NY was injected in the pedunculopontine nucleus on one side and in the substantia nigra on the other. Following these injections cells containing the tracer delivered in the pedunculopontine nucleus were found to be 5-6 times less numerous than those labeled after substantia nigra injections...     

Suppression of cell firing in the substantia nigra by caudate nucleus stimulation

Cats anesthetized with barbiturates show a unique 8–12/sec continuous rhythmic activity in the subthalamic nucleus and ventral tegmental region which may be correlated with the “barbiturate tremor.” Pallidal stimulation inhibits subthalamic nucleus slow-wave and single-unit activity, while nigral stimulation produces a phasic discharge in subthalamic neurons. In contrast to pallidal stimulation, caudate stimulation does not inhibit the firing of subthalamic nucleus cells. In view of this and the action of the substantia nigra upon the subthalamic nucleus, we studied the effects of caudate activation upon extracellularly recorded single unit responses in the nigra of barbiturate-anesthetized cats. Fifty-one units were analyzed. Of these, 24 were localized to the tegmentum just above the substantia nigra, 25 in the nigra, and two in the cerebral peduncle. The predominant effect of single caudate stimuli was suppression of firing of nigral (95%) or tegmental (58%) cells for either 70 or 140 msec, or more. These effects were seen in both medial and lateral portions of the nigra, and at rostral and caudal levels of the nucleus. No short-latency spikes were seen in nigral cells following caudate stimulation, and only a few in units localized to the tegmentum. In the barbiturate anesthetized cat, caudate stimulation leads to a suppression of firing of cells throughout the substantia nigra.     

Inhibition of neuronal activity of the substantia nigra by noxious stimuli and its modification by the caudate nucleus

In urethane-anesthetized rats discharges of neurons of substantia nigra, pars compacta (SNC) were recorded extracellularly after natural somatic sensory stimulation and electrical stimulation of peripheral sensory nerves.

(1) Among different modalities of somatic sensory stimulation tested, noxious stimuli were effective in reducing spontaneous discharges of SNC neurons. The inhibition appeared with a concomitant increase of spike amplitude. The same inhibitory effect was obtained by stimulating the sciatic nerve (SC) repetitively. In response to single shock stimulation of the SC the inhibition occurred at an average latency of 39.6 msec (S.E. 1.6 msec) and lasted for 221.6 msec on average (S.E. 10.8 msec).

(2) The SC-induced inhibition of SNC neurons failed to reliably block orthoand antidromic discharges evoked from the caudate nucleus (Cd).

(3) In rats with the Cd lesioned the SC-induced inhibition was longer lasting than in controls. When the Cd was stimulated concurrently with SC stimulation, the inhibition from the SC was weakened.

(4) In a majority of SNC neurons, their inhibition by SC stimulation was antagonized by intravenous injection of haloperidol.

Effect of substantia nigra stimulation on spontaneous unit activity in the caudate nucleus

A wide range of spontaneous unit activity (0.1–15 spikes/sec) was observed in the caudate nucleus of rats anesthetized with urethane. All units did not respond by driven activity following stimulation of the substantia nigra. However, 71% of this population responded by significantly increased or decreased firing rates. It is suggested that unit that exhibit spontaneous activity in the caudate nucleus and which respond to stimulation of the substantia nigra have polysynaptic connections, and those units which do not discharge spontaneously but respond to stimulation of the substantia nucleus by driven action potentials have monosynaptic connetion to the caudate nucleus.     

Relationship between the striatal system and amygdaloid paroxysmal activity

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.     

Efferent connections of the caudate nucleus, including cortical projections of the striatum and other basal ganglia: an autoradiographic and horseradish peroxidase investigation in the cat

Tritiated tracer was injected into the head of the caudate nucleus in cats. Following such injections, labeling is present within extensive regions of both the globus pallidus and entopeduncular nucleus, where it presents a mottled or meshlike appearance. These projections are topographically organized in that there is simple correspondence between the mediolateral, dorsoventral, and rostrocaudal origin of the caudate projection and its input to the globus pallidus and entopeduncular nucleus. Transported tracer is also present within the substantia nigra, where it is most abundant within the pars reticularis. However, distinct labeling also overlies cells of the pars compacta, and lesser amounts of labeling are present within the pars lateralis and within the retrorubral area. Following injections of horseradish peroxidase into the caudate nucleus, and subsequent tissue processing by the tetramethylbenzidine (TMB) method of Mesulam ('78), labeled anterograde fibers are present in abundance within the globus pallidus, entopeduncular nucleus, and all subdivisions of the substantia nigra, thus confirming the autoradiographic findings. Also, it is especially obvious in this HRP material that, contrary to previous degeneration studies, both the rostromedial and caudolateral parts of the pars lateralis of the substantia nigra contain numerous anterogradely labeled fibers. Retrogradely labeled neurons are also present within the substantia nigra of these same tissue sections, where they are most abundant within the pars compacta, but lesser numbers of labeled neurons are also present within the pars reticularis, pars lateralis, retrorubral area, and ventral tegmental area on the ipsilateral side, and all of these same subdivisions of the substantia nigra on the contralateral side. Also, within the subthalamic nucleus in these experiments, there are anterogradely labeled fibers, as well as retrogradely labeled neurons, which are interpreted to represent a reciprocal connection between the subthalamic nucleus and the striatum. In a separate series of experiments, horseradish peroxidase was injected into the motor cortex-specifically into the anterior sigmoidal gyrus. Following such injections, labeled neurons representing afferents to the motor cortex are found in all subcortical nuclei commonly known as the "basal ganglia," including the caudate nucleus, putamen, globus pallidus, entopeduncular nucleus, substantia innominata, nucleus of the diagonal band of Broca, medial septal nucleus, claustrum, and basolateral amygdaloid nucleus.     

Caudate evoked synaptic activities in nigral neurons

Intracellular recordings from neurons in the substantia nigra have revealed three varieties of monosynaptic PSPs in response to stimulation of the ipsilateral head of the caudate nucleus: short (3–5 msec) latency EPSPs; short (3–5 msec) latency IPSPs; and long (15–20 msec) latency IPSPs. The data indicate that at least three efferent fiber systems link the caudate to the nigra: two fast conducting axonal systems of comparable diameters mediate the short-latency PSPs whereas a slow conducting axonal system mediates the long-latency PSPs. The caudate evoked long-latency IPSPs in nigral neurons were preceded by antidromic and orthodromic potentials in the motor cortex; these cortical potentials are regarded as epiphenomena. The dual, facilitatory-inhibitory control of caudate on nigral neurons is consonant with the proposal that the caudate self-regulates its input from the nigra. The caudate-evoked EPSPs in nigral neurons are sine qua non for the operation of the caudato-nigrothalamic projection system.     

Rotatory behavior induced by glycine injected into the substantia nigra of the rat.

Implantation of crystalline glycine and dopamine into the substantia nigra of the rat caused the rat to turn away from the injected side. This response is similar to that observed after electrical stimulation of the substantia nigra, or after amphetamine administration when the contralateral substantia nigra has been previously damaged with 6-hydroxydopamine. Rotatory behavior was not observed after injection of glycine into the caudate nucleus, whereas dopamine did induce this effect, as previously demonstrated.     

The functional role of the nucleus accumbens in the control of the substantia nigra: Electrophysiological investigations in intact and striatum-globus pallidus lesioned rats

The effects of electrical stimulation of the nucleus accumbens on the activity of identified substantia nigra neurons were studied in intact and lesioned rats. The latter had both the caudate-putamen complex and globus pallidus destroyed by electrolytic lesions. In intact rats a total of 42 of 107 neurons (39.2%) responded to stimulation of the nucleus accumbens. Of the 107 neurons 32 (29.8%) were inhibited and 10 (9.4%) were excited. Pure short inhibitions, long latency inhibitions and excitations followed by inhibition were found in both parts of the substantia nigra. Pure long lasting inhibitions were determined on pars compacta cells only. In lesioned animals, in which the coactivation of striatal and/or cortical fibers traversing the accumbens region was avoided, the percentage of responsive neurons decreased to 20% (23/115). The predominant responses recorded in this situation were pure inhibitions of pars compacta cells (14/46) and long latency inhibitions of pars reticulata neurons (7/69). No pure excitation or excitation-inhibition sequence was recorded. In the two sets of experiments 5 cells were activated antidromically from the nucleus accumbens. The results provide electrophysiological evidence for an inhibitory pathway from the nucleus accumbens to the substantia nigra. The low percentage of responsive neurons, the lack of excitatory responses, the paucity of reciprocal connections and the different inhibitory effects on the two populations of nigral neurons demonstrate that the functional role of the nucleus accumbens in controlling the substantia nigra differs from that exerted by the striatum.     

Neurological disturbances, nigrostriate synapses, and iontophoretic dopamine and apomorphine after haloperidol

The hypothesis that haloperidol blocks the effects of dopamine in the caudate nucleus was tested. Nigrostriate synaptic transmission was studied by recording single-unit responses and evoked potentials and by microiontophoresis in the caudate nucleus of unanesthetized cats. The substantia nigra was stimulated with stereotaxically placed electrodes. Cats were chronically treated with doses of haloperidol sufficient to induce its motor system side effects. In acute experiments performed after the development of parkinsonian-like motor disorders including bradykinesia and tremor at rest, neurons responded to stimulation of the substantia nigra and to the microiontophoresis of dopamine in manners and in proportions indistinguishable from those seen in normal cats. Apomorphine inhibited three of nine neurons also inhibited by dopamine. Nigrostriate evoked potentials of normal waveform and amplitude were present. In another group of cats, nigrostriate evoked potentials were recorded before and after a single dose of haloperidol. This single dose did not modify the evoked potentials during the time when biochemical changes are known to be occurring. In additional experiments, the response of individual neurons to iontophoretically applied dopamine was recorded before, during, and after the administration of a single dose of haloperidol. The amount of dopamine necessary to reduce glutamate-evoked excitation by 50% was not changed by the injection of haloperidol. In conclusion, a change in the effectiveness of dopamine on neurons in the caudate nucleus (including some also influenced by apomorphine) could not be detected after systemic haloperidol. Nigrostriate synaptic transmission (including that to some neurons also influenced by dopamine) was not blocked. These findings are not consistent with the theory that the behavioral effects of systemically administered haloperidol are caused by a blockade of dopaminoceptive synapses in the caudate nucleus.     

Excitation and inhibition processes in the neurons of the thalamic motor nuclei of normal cats and following an N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced lesion of the nigrostriatal dopaminergic system

Peculiarities of excitation and inhibition evoked in motor thalamic nuclei (VA-VL) neurons by electrical stimulation of red nucleus were studied on intact cats and after injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 5 mg/kg i.m., p.d. during five days). Two days after the last injection as much as 48% of nigral neurons were destroyed and the content of dopamine in the caudate nucleus fell to 30% as compared to intact animals. Before acute experiments all cats were anaesthetized with ketalar and immobilized with myorelaxine. It was found that MPTP injections caused a decrease of the inhibition duration and effectiveness in relay and nonrelay VA-VL neurons. The inhibition deficiency was accompanied by shortening of latencies of orthodromic responses evoked by red nucleus stimulation and facilitation of antidromic spikes invasion into somata of relay neurons after motor cortex stimulation. It was suggested that the reduction of GABAergic nigro-thalamic influences modulated by dopamine underlay the developing deficiency of inhibition.     

Erratum

Tritiated tracer was injected into the head of the caudate nucleus in cats. Following such injections, labeling is present within extensive regions of both the globus pallidus and entopeduncular nucleus, where it presents a mottled or meshlike appearance. These projections are topographically organized in that there is simple correspondence between the mediolateral, dorsoventral, and rostrocaudal origin of the caudate projection and its input to the globus pallidus and entopeduncular nucleus. Transported tracer is also present within the substantia nigra, where it is most abundant within the pars reticularis. However, distinct labeling also overlies cells of the pars corapacta, and lesser amounts of labeling are present within the pars lateralis and within the retrorubral area. Following injections of horseradish peroxidase into the caudate nucleus, and subsequent tissue processing by the tetramethylbenzidine (TMB) method of Mesulam (1978), labeled anterograde fibers are present in abundance within the globus pallidus, entopeduncular nucleus, and all subdivisions of the substantia nigra, thus confirming the autoradiographic findings. Also, it is especially obvious in this HRP material that, contrary to previous degeneration studied, both the rostromedial and caudolateral parts of the pars reticularis of the substantia nigra contain numerous anterogradely labeled fibers. Retrogradely labeled neurons are also present within the substantia nigra of these same tissue sections, where they are most abundant within the pars compacta, but lesser numbers of labeled neurons are also present within the pars reticularis, pars lateralis, retrorubral area, and ventral tegmental area on the ipsilateral side, and all of these same subdivisions of the substantia nigra on the contralateral side. Also, within the subthalamic nucleus in these experiments, there are anterogradely labeled fibers, as well as retrogradely labeled neurons, which are interpreted to represent a reciprocal connection between the subthalamic nucleus and the striatum. In a separate series of experiments, horseradish peroxidase was injected into the motor cortex–specifically into the anterior sigmoidal gyrus. Following such injections, labeled neurons representing afferents to the motor cortex are found in all subcortical nuclei commonly known as the “basal ganglia,” including the caudate nucleus, putamen, globus pallidus, entopeduncular nucleus, substantia innominata, nucleus of the diagonal band of Broca, medial septal nucleus, claustrum, and basolateral amygdaloid nucleus.     

Behavioral alterations and loss of caudate modulation in the centrum medianum-parafascicular complex of the cat following electrolytic lesions of the substantia nigra

Extracellular activity in the centrum medianum-parafascicular complex was examined following electrolytic lesions of the substantia nigra in the cat. Three major changes were observed in the activity of these polysensory medial thalamic neurons: (1) normally quiescent in the intact animal, about 70% of the neurons now dsiplayed spontaneous activity; (2) many of these spontaneously active neurons no longer responded to caudate stimulation and the responses to sensory stimulation were not changed; and (3) while caudate stimulation alone did inhibit some neurons, such stimulation in a conditioning test procedure often failed to inhibit the test response to limb stimulation which ‘broke through’ the inhibitory period. All of these changes were correlated with the extent of damage to the ipsilateral substantia nigra.Additionally, a noticeable change was observed in the behavior of the lesioned animals; intense circling, contralateral to the side of the lesion, persisted for several days following surgery. Other symptoms were arrest reactions, abnormal rhythmic pawing and sluggishness of movement.The results indicate that the substantia nigra is an important element in funneling caudatofugal activity to the centromedian-parafascicular complex where it interacts with, and modulates incoming sensory activity. The loss of this modulation and the removal of a tonic background inhibition, indicated by the increased proportion of spontaneously active neurons, may be important factors in producing the observed behavioral abnormalities.     

Global reduction in cerebral blood flow and metabolism elicited from intrinsic neurons of fastigial nucleus

We sought to determine whether the global increase in regional cerebral blood flow (rCBF) produced by electrical stimulation of the rostral cerebellar fastigial nucleus (FN) is a consequence of excitation of intrinsic neurons of the FN or of axons of fibers passing through or projecting into it. Studies were conducted in rats anesthetized with chloralose, paralyzed and ventilated. rCBF was measured with [¹⁴C]iodoantipyrine as tracer and regional cerebral glucose utilization (rCGU) by [¹⁴C]2-deoxyglucose in homogenates of 11 brain regions. Neuronal perikarya in FN were excited chemically by local microinjection of the glutamate analogue kainic acid (KA) (5 nmol in 100 nl). KA elicited a transient and significant fall of arterial pressure and heart rate, the fastigial depressor response (FDR). Associated was a significant and symmetrical reduction in rCBF, to 44% of control in all regions except medulla. The response was site- and agent-specific and unrelated to the hypotension. KA also significantly and proportionally reduced, to 52% of control, rCGU in the same 10 areas of brain. In all regions the magnitudes of the reductions in rCBF and rCGU elicited by KA were linearly related. Intrinsic neurons of FN were chronically destroyed by local microinjection of the excitotoxin ibotenic acid (IBO) (10 μg/μl in 0.4 μl). Destruction of intrinsic FN neurons had no effect on resting rCBF nor on the global cerebrovascular vasodilation elicited by electrical stimulation of the FN. We conclude that: (a) excitation of intrinsic neurons of FN elicits a widespread reduction of cerebral metabolism and, secondarily, blood flow; (b) FN neurons do not exert a long-term tonic influence on brain blood flow nor metabolism; (c) the global increase in rCBF elicited by electrical stimulation of the FN is a consequence of excitation of axons projecting into or through the nucleus.     

Caudate unit activity and somal diameters in intact and nigral lesioned cats

In a search for morphofunctional relationships in the head of the caudate nucleus (CN), we recorded extracellular unit activity in intact cats and in cats that had received bilateral injections of 6-OHDA into the substantia nigra (SN) 30 days previously. Only units firing spontaneously and continuously for 2 min were studied. In dorsal regions, potentials were small and iterative at almost constant intervals; the somal diameters were relatively small. In the ventrolateral region, potentials were bigger and appeared in bursts; somal diameters were significantly larger (p less than 0.05). For the centromedial region a histogram of numbers of neurons as a function of diameters revealed a Gaussian distribution extending from small to large neurons. Most dorsal neurons increased their firing rate to radial nerve, visual, SN, and/or nucleus centralis medialis (NCM) stimulation. Ventral neurons usually responded with excitation followed by long lasting inhibition, particularly to SN and NCM stimulation. A few neurons responded to all four inputs and some showed long-lasting potentiation in response to low frequency stimulation, suggesting a more general function. Greatest convergence (65%) was found for NCM and SN inputs. In lesioned cats, there was no SN driving, NCM's inhibitory actions almost disappeared, and the excitatory action of the other stimuli was reduced.     

Kainic acid-induced substantia nigra seizure in rats: behavior, EEG and metabolism

RATIONALE: In order to clarify the role of substantia nigra pars reticulata (SNr) upon the development of epileptic seizure, kainic acid (KA) was injected into a unilateral SNr. MATERIALS AND METHODS: Wistar rats weighing 250-350 g were used. A stainless-steel cannula and depth electrode were inserted stereotaxically into the left substantia nigra pars reticulata (SNr). At 7 days after surgery, 1.0 microg of KA was injected into the left SNr. Experiment 1: In eight rats, behavior and electroencephalograms (EEG) were continuously recorded for about 30 h, and intermittently monitored following 1 month. Experiment 2: Two hours after KA injection into SNr, rats demonstrated status epilepticus. Then, 100 microCi/kg of [(14)C]2-deoxyglucose (2-DG) was intravenously injected in seven rats, and the rats were processed for autoradiographic study. RESULTS: Changes in behavior and EEG: On EEG, a secondary generalized seizure status was observed at about 70 min after KA injection. In video, limbic seizure manifestations such as salivation were observed as a initial symptom and followed by rolling and generalized tonic seizures. [(14)C]deoxyglucose autoradiographic study demonstrated increased local cerebral glucose metabolism in the medial and lateral septal nucleus, substantia nigra, hippocampus, parietal cortex, piriform cortex, medial and lateral geniculate nucleus, anterodorsal, lateral and ventral nucleus of the thalamus, amygdala and midbrain reticular formation. SUMMARY: The result suggested that the substantia nigra played an important role in the secondary generalization in the substantia nigra seizure model due to the decreased function of the GABAergic projection system induced by an excessive epileptic excitation of SNr.     

Intracellular analysis of the development of responses of caudate neurons to stimulation of cortex, thalamus and substantia nigra in the kitten

Intracellular recordings were made from caudate neurons in anesthetized kittens of 2-72 days of age. In adult cats, results of intracellular recordings indicate that caudate neurons respond most frequently to stimulation of their major afferents from cortex, thalamus and substantia nigra with a sequence of excitation followed by inhibition (EPSP-IPSP sequence). The results of the present study show that the prominent IPSP of this sequence is not well developed in young kittens and does not reach adult values in terms of frequency of occurrence until beyond 40 days of age. Amplitude and duration of the IPSP evoked by cortical stimulation also did not reach adult values until beyond 40 days of age. In contrast, EPSPs can be evoked in the youngest kittens by stimulation of afferents to the caudate. These findings suggest that the caudate nucleus may alter its role during development. In early postnatal periods it functions as a simple relay system transmitting incoming information to its outputs in a relatively unaltered fashion. Later in development it becomes a system capable of complex modulation and filtering of neural information.     

Release of dopamine evoked by electrical stimulation of the motor and visual areas of the cerebral cortex in both caudate nuclei and in the substantia nigra in the cat

The effects of unilateral focal electrical stimulation of the deep cerebellar nuclei on the activity of the nigrostriatal dopaminergic neurons on both sides of the brain were examined in halothane anaesthetized cats. For this purpose, push-pull cannulae were inserted into both caudate nuclei and both substantia nigrae, and the release of [3H] dopamine ([3H]DA) continuously formed from [3,5-3H]L-tyrosine was estimated in superfusates. The unilateral electrical stimulation of the right cerebellar dentate nucleus induced a long-lasting increase in the release of [3H]DA in the left caudate nucleus and a simultaneous decrease in the release of [3H]transmitter in the right caudate nucleus. These changes were associated with opposite fluctuations in the release of [3H]DA from the corresponding substantia nigrae. Thus, the electrical stimulation of the right dentate nucleus induced a pronounced decrease in the release of the [3H]-amine in the [3H]transmitter in the corresponding substantia nigra, whereas the activity of the contralateral substantia nigra, whereas the release in the ipsilateral substantia nigra was simultaneously increased. In contrast, the unilateral electrical stimulation of the right cerebellar fastigial nucleus resulted only in an increased release of [3H]DA in the ipsilateral (right) caudate nucleus, associated with a decreased release of the [3H]transmitter in the corresponding substantia nigra, whereas the activity of the contralateral (left) dopaminergic system was not significantly affected. These results support a direct functional interaction between the cerebellum and the basal ganglia. They also suggest that the release of DA from dopaminergic axonal terminals is inversely correlated to the extent of the transmitter release from dendrites.     

A novel vasodepressor response elicited from the rat cerebellar fastigial nucleus: the fastigial depressor response

We sought to determine by using kainic acid (KA), an agent stimulating neuronal cell bodies but not fibers, whether the elevations in arterial pressure (AP) and heart rate (HR) elicited by electrical stimulation of the cerebellar fastigial nucleus (FN) are due to excitation of local neurons in FN or fibers passing through the area. Rats were anesthetized (chloralose 40 mg/kg), paralyzed (tubocurarine) and artificially ventilated. Electrical stimulation of FN (50 Hz, 10–100 μA) increased AP and HR. In contrast restricted microinjections of KA (0.05–5 nmol/100 nl) in FN elicited a sustained, dose-dependentdecrease in AP and HR. The response is not due to diffusion of KA to adjacent sites. Excitation by KA of neurons intrinsic to FN elicits a heretofore unrecognized vasodepressor response, the fastigial depressor response.