The anterior pretectal nucleus: a proposed role in sensory processing

Four nuclei of the pretectal complex, the olivary pretectal nucleus, the medial pretectal nucleus, the nucleus of the optic tract and the posterior pretectal nucleus, all have a demonstrated role in visual function. In contrast, the anterior pretectal nucleus (APtN) has no inputs from retina and has few outputs to visual accessory nuclei. The APtN has connections with areas associated with sensory functions and it has been suggested that this nucleus may have a role to play in somatosensory processing. An increasing number of behavioural and electrophysiological studies support this view. Brief low-intensity electrical or chemical stimulation of the APtN causes antinociception in the tail flick test in both unanaesthetised and anaesthetised animals. This inhibition of the tail flick response is attenuated by naloxone, alpha-adrenoceptor antagonists and muscarinic cholinergic receptor antagonists. Electrical stimulation of the APtN is similarly effective in the paw pressure and formalin tests. APtN stimulation also causes a brief inhibition of the tooth pulp-evoked jaw opening reflex. studies with [C14]2-deoxyglucose indicate that peripheral noxious stimuli will cause an increase in metabolic activity within the APtN. Animals with electrodes placed in the APtN will self-administer electrical stimulation and this can reduce the aversive and autonomic effects of stimulating the ventromedial hypothalamus. Part of the antinociceptive effects of stimulating the APtN are due to a descending inhibition of spinal dorsal horn projection neurones. Multireceptive neurones deep in the dorsal horn are inhibited by APtN stimulation. In contrast, superficial projection neurones that respond to intense cutaneous stimuli are excited by APtN stimulation. The APtN receives an excitatory input from low-threshold afferents via the dorsal column pathway and a high-threshold excitatory drive from superficial cells projecting through the dorsolateral funiculus. The excitatory input from the dorsal columns may well participate in the long-term inhibition of spinal projection neurones evoked by dorsal column stimulation. These ascending excitatory pathways may also be important to the long-term activation of descending inhibition from the APtN.     

Quantitative and somatotopic mapping of neurones in the trigeminal mesencephalic nucleus and ganglion innervating teeth in monkey and baboon

Neurones of the trigeminal mesencephalic nucleus (Mes V) and ganglion innervating the periodontium of incisor, canine and molar teeth in 10 monkeys and 10 baboons were counted and mapped using the horseradish peroxidase (Hrp), retrograde axonal transport method. Periodontal afferent neurones of all these teeth were well represented in the Mes V, although the incisors had a significantly higher number of labelled neurones than the canines or molars. The primary cell bodies of the periodontal afferents were located mainly in the caudal part of the ipsilateral Mes V from the level of the inferior colliculus to the floor of the fourth ventricle in the pons. The caudal periodontal Mes V neurones may be favourably located to make collateral connections with the trigeminal motor nucleus for jaw reflexes. Incisors and canines had a large and predominantly ipsilateral representation of Hrp-labelled neurones in the ganglion. In contrast, molar representation in the ganglion was sparse and all labelled neurones supplied ipsilateral teeth. The maxillary and mandibular teeth had a somatotopic distribution within the respective maxillary (middle) and mandibular (posterolateral) compartments of the trigeminal ganglion. It is suggested that the anterior teeth with greater connections to the Mes V and the ganglion may impart greater sensory perception and be involved in jaw reflexes to ensure a good occlusal relation during mastication, while the afferent connections of the molars may initiate complex jaw reflexes during the occlusal phase of mastication.     

Reactions of red-nucleus neurons in the alert cat to cutaneous stimulation

Responses of the red nucleus (RN) neurones to cutaneous stimulation were studied in unanaesthetized chronic cats by means of microelectrode technique. It was revealed that the reactions were predominantly excitatory and the RN neurons had larger receptive fields covering one half of the body or all the limbs of the animal. The somatotopic principle of the cutaneous representation in RN was shown. The destruction of the cerebellar nuclei and sensorimotor cortex caused the lowering of the background activity of the RN neurones, changed their responses to cutaneous stimulation, as well as the narrowing and redistribution of the peripheral receptive fields. With all the changes described, the somatotopic character of the cutaneous representation in RN as preserved, though a large majority of RN neurones (52,8%) did not show this somatotopic distribution. The cerebellum is the main collector in transferring the cutaneous impulsation to the RN. In awake cats there were predominantly involved spinocerebellar pathways, activated by the flexor reflex afferents. The participation of the sensorimotor cortex in the reaction under study is revealed by the phenomenon of sprouting of the corticorubral axon terminals from the dendritic portions to the neuronal somata of RN.     

Tooth pulp neurons in the caudal medulla oblongata of the cat

The medulla oblongata caudal to the obex was explored for neurons responsive to tooth pulp (TP) stimulation in cats. Four different subclasses of TP neurons were found. The latter included TP specific (TPS) neurons, trigeminal wide dynamic range (trigeminal WDR) neurons with TP input, trigeminal subnucleus reticularis ventralis (trigeminal SRV) neurons with TP input and convergent reticular formation (convergent RF) neurons with TP input. TPS neurons were located in the dorsal marginal rim of the trigeminal subnucleus caudalis, i.e., in the marginal layer or the outer zone of substantia gelatinosa. WDR neurons with TP input were found in the neck region of medullary dorsal horn which corresponds to the lateral part of subnucleus reticularis dorsalis (SRD). Trigeminal SRV neurons with TP input were located in the lateral part of SRV. Convergent RF neurons with TP input were found in the middle third of the caudal bulbar RF consisting of SRD and SRV. Both TPS neurons and WDR neurons with TP input included trigeminothalamic neurons as evidenced by the antidromic activation from the nucleus ventralis posteromedialis of the contralateral thalamus. A significant proportion of both trigeminal SRV and convergent RF neurons with TP input were antidromically activated by stimulation of the nucleus centralis lateralis of the contralateral thalamus. The former two subclasses may subserve the sensory-discriminative aspect of toothache, while the latter two subclasses, the emotional-motivational aspect.     

Reversal of fusimotor reflex responses during locomotion in the decerebrate cat

The effect of brief trains of electrical stimulation, at 2, 3 and 20 x threshold (T), of cutaneous afferents in the medial plantar nerve on the discharges of single medial gastrocnemius static and dynamic gamma-efferents has been investigated at rest and during locomotion in a decerebrate cat preparation. The units were classified as dynamic (10 units) or static (10 units) indirectly on the basis of their resting and locomotor discharge characteristics. Responses were assessed by calculating the change in mean gamma-rate during the 100 ms after stimulus onset compared with a control period. At rest, most dynamic neurones were inhibited by stimulation at 2T (9 of 10 units) and above. In contrast, the resting responses of most static neurones were excitatory at 2T (9 of 10 units) and 3T, while 20T produced static gamma-effects that varied in sign. During locomotion the responses of both types of gamma-efferent were phase related. Two patterns were observed with dynamic units. For seven dynamic neurones, at stimulus levels of 2T (7 units) and above, responses during electromyogram (EMG) bursts were inhibitory while those between bursts were not significantly different from zero. However, for three other dynamic units, a phase-related reversal of reflex responses was observed at some stimulus intensities (always 2T, 3 units) comprising inhibition during, and excitation between, EMG bursts. For static neurones, inhibitory (never excitatory) responses occurred during walking at stimulus intensities of 2T (10 units) and above. The locomotor responses of static units were maximum during (3 units) or between (7 units) EMG bursts and were minimum in the opposite phase of EMG activity. A task-related reversal of reflex responses was thus generally apparent (9 of 10 units) to low intensity stimulation (2T) for static gamma-efferents during locomotion (inhibition) compared with rest (excitation). During locomotion there was a significant linear relation between the magnitude of response and the background gamma-rate for static units and those dynamic units that did not exhibit phase-related reflex reversal (total, 17 units). For dynamic gamma-efferents, inhibition at rest and during locomotion occurred at short (spinal) latencies which were not significantly different and are consistent with the involvement of the same interneuronal pathway. We conclude that pathways of opposite sign may dominate the responses of fusimotor neurones to low threshold cutaneous afferents from the plantar surface of the foot depending on behavioural context. Furthermore, the cutaneous reflex responses of both types of gamma-motoneurones during locomotion appear to vary with the source of the afferent input and do not constitute a general excitatory drive. The results are discussed in relation to the role and reflex control of the fusimotor system.     

Properties of relay cells in cat's lateral geniculate nucleus: a comparison of W-cells with X- and Y-cells

1. Observations are presented on the physiological properties of W-, X-, and Y-type relay cells in the cat's lateral geniculate nucleus (LGN). Emphasis is placed on the most recently recognized type, W-cells; data are presented on X- and Y-cells by way of comparison. 2. Seventy-seven W-cells were recognized on 70 microelectrode penetrations through the LGN. They resembled W-type retinal ganglion cells in their responses to visual stimuli. Tonic (on-center and off-center) W-cells, phasic (on-, off- and on-off center) W-cells, suppressed-by-contrast, and color-coded cells were recognized. 3. W-type relay cells also resembled retinal W-cells in their maintained activity and receptive field-center diameters. 4. W-type relay cells comprised 11.5% X-cells 48.4%, and Y-cells 22.3% of all LGN cells encountered on a reference sample of 62 electrode tracks. W-cells were found in laminae C, C1, and C2, comprising 36.5% of the sample in these laminae, but were not encountered in laminae A or A1. X- and Y-cells were found in laminae A, A1, and C. Within lamina C there was a tendency for X- and Y-cells to be located dorsal to W-cells. There was thus a substantial dorsoventral segregation of W-cells from X- and Y-cells. W-cells being found in the ventral parvocellular component of the dorsal LGN. 5. Cells considered to be W-type relay cells were shown to respond to electrical stimulation of the optic nerve and chiasm at latencies which were longer than those of X- and Y-cells, and were consistent with their receiving monosynaptic input from retinal W-cells. Geniculate W-cells of all subtypes were activated antidromically from the visual cortex. Their antidromic latencies were, on the average, longer than for Y- or X-cells, indicating that W-type relay cells had slower axons as well as slower retinal afferents, than X- or Y-cells. 6. The visual cortex thus appears to receive input from all three major types of retinal ganlion cells (W-, X-, and Y-cells) relayed separately, in parallel, by different groups of relay cells.     

Multiple-tooth receptive fields of single human periodontal mechanoreceptive afferents

1. Single-unit impulse activity from 25 mechanoreceptive afferents was recorded in the human inferior alveolar nerve using tungsten microelectrodes. All of these afferents were considered to originate in periodontal receptors because they showed responses to mechanical stimulation of one or more teeth but not to stimulation of the gingiva. 2. For each afferent isolated, forces with "ramp-and-hold"-shaped profiles of similar magnitudes (261 +/- 21 mN, mean +/- SD) were applied to the incisors, the canine, and the first premolar on the recording side, and the contralateral central incisor in four horizontal directions: lingual, labial, mesial, and distal. For a few of the afferents, forces were also applied in the axial directions (up and down). Both static and dynamic response components were analyzed. 3. For about one half of the tested afferents, the receptive fields were restricted to a single tooth. The remainder (52%) responded to stimulation of a group of teeth (on average 3.1 teeth), which typically showed contact between their crowns. 4. Afferents responding to loading of multiple teeth showed their strongest responses to forces applied to a particular tooth, with a gradual decline in the responsiveness to the adjacent teeth. 5. The stimulation directions eliciting the strongest afferent responses for the most sensitive tooth were approximately evenly distributed over the four stimulation directions, except for some bias toward the lingual direction. In contrast, loading of the adjacent teeth most often showed the strongest responses in the mesial or distal directions, in most cases toward the most sensitive tooth.(ABSTRACT TRUNCATED AT 250 WORDS)     

Convergence of skin reflex and corticospinal effects in segmental and propriospinal pathways to forelimb motoneurones in the cat

The organization of facilitatory convergence from cutaneous afferents (Skin) and the corticospinal tract (pyramidal tract, Pyr) in pathways to forelimb motoneurones of mainly distal muscles was studied in anaesthetized cats by analysing postsynaptic potentials (PSPs), which were spatially facilitated by combinations of stimuli to the two sources at different time intervals. Conditioning Pyr volleys facilitated Skin-evoked PSPs of fixed (1.2-3.6 ms) central latencies (Skin PSPs), suggesting that disynaptic and polysynaptic skin reflex pathways are facilitated from the pyramidal tract. The shortest latencies (1.2-1.7 ms) of pyramidal facilitation suggested direct connection of pyramidal fibres with last order neurones of skin reflex pathways. Conditioning Skin volleys facilitated Pyr-evoked PSPs of fixed, mostly disynaptic latencies (1.0-2.5 ms; Pyr PSPs), suggesting that pyramido-motoneuronal pathways are facilitated from Skin at a premotoneuronal level. The shortest pathway from skin afferents to the premotor neurones appeared to be monosynaptic. Although Pyr and Skin volleys were mutually facilitating, the facilitation curve of Pyr PSPs and that of Skin PSPs were discontinuous to each other, with the peak facilitation at different Skin-Pyr volley intervals. Transection of the dorsal column (DC) at the C5/C6 border had little effect on the latencies or amplitudes evoked by maximal stimulation and the pyramidal facilitation of Skin PSPs. In contrast, the facilitation of Pyr PSPs by Skin stimulation was greatly decreased after the DC transection, and the facilitation curve of Pyr PSPs was continuous to that of Skin PSPs, with no separate peak. Latencies of Pyr PSPs ranged similarly to those in DC intact preparations. More rostral DC transection (C4/C5 border) reduced Skin-facilitated Pyr excitatory PSPs (EPSPs) less than C5/C6 lesions, suggesting that the C5 segment also contains neurones mediating Skin-facilitated Pyr EPSPs. The results show that convergence from skin afferents and the corticospinal tract occurs at premotor pathways of different cervical segments. We suggest that corticospinal facilitation of skin reflex occurs mostly in the brachial segments and Skin facilitation of cortico-motoneuronal effects takes place largely in the rostral cervical segments and partly in the brachial segments.     

Response of the hypothalamic neurons to stimulation of the vestibular nerve and lateral vestibular nucleus in rabbits

Effects of single, double, and rhythmic stimulation upon hypothalamic neurons responding to the 1st excitatory phase of lateral vestibular nucleus stimulation, were studied. The data obtained show that activation of some hypothalamic neurons following stimulation of the lateral vestibular nucleus has a monosynaptic character. The findings suggest that ascending afferents from the lateral vestibular nucleus to the hypothalamus pass via oligo- as well as polysynaptic pathways.     

Capsaicin in the 4th ventricle abolishes retching and transmission of emetic vagal afferents to solitary nucleus neurons

Systemic tachykinin NK1 receptor antagonists and resiniferatoxin are known to abolish vomiting mediated by vagal afferents. Emetic vagal afferents have been shown to make synaptic contact with neurons in the medial solitary nucleus. These results suggest that substance P participates in the synapse as a mediator. To examine this possibility, the effects of 4th-ventricular application of capsaicin (0.033-33 mM, 20-30 microl) and resiniferatoxin (1.6-160 microM, 20-30 microl) on the activity of neurons in the medial solitary nucleus and fictive retching induced by vagal stimulation were observed in paralyzed decerebrate dogs. Capsaicin (33 mM) and resiniferatoxin (160 microM) initially increased the neuronal firing and occasionally produced retching, then abolished both neuronal and retching responses. However, stimulation of the medial solitary nucleus continued to provoke retching. Field potential changes in the medial solitary nucleus evoked by pulse-train vagal stimulation decreased in amplitude, but did not disappear. Latencies of neuronal firing and evoked potentials were about 300 ms. These results suggest that emetic vagal afferents are capsaicin-sensitive C fibers which may have substance P as an excitatory transmitter or modulator.     

Electrophysiological and Fos immunohistochemical evidence for the excitatory nature of the parafascicular projection to the globus pallidus

Extracellular recordings and immunohistological detection of c-Fos-like immunoreactive proteins were used to determine the synaptic effect of the parafascicular projection to the globus pallidus. Electrical stimulation of the parafascicular neurons induced a single-spike excitatory response with a stable latency of 2.3 ms, suggesting a monosynaptically driven effect. Pharmacological stimulation of the parafascicular nucleus with carbachol increased tonically the pallidal discharge rate by 142%. The discharge rate of the pallidal neurons was described by 37% in parafascicular-lesioned rats. These results demonstrate the excitatory nature and the tonic action of the parafasciculopallidal projection. Carbachol activation of parafascicular neurons also induced the synthesis of c-Fos-like immunoreactive proteins in the pallidal neurons. Control experiments in subthalamic-lesioned rats showed that the parafascicular excitation of the pallidal neurons remained, but both electrophysiological and expression of c-Fos-like immunoreactive proteins were attenuated. This suggests that the direct parafascicular excitation of the pallidal neurons is indirectly reinforced by the previously described parafascicular excitatory input to the subthalamic nucleus. Conversely, the effect of this last input to the subthalamic nucleus is dramatically enhanced in rats with pallidal lesion. Our results demonstrate the complex role of the parafascicular nucleus in activating both the globus pallidus and the subthalamic nucleus, two closely related structures. These results illustrate the integrative capacities of the globus pallidus, whose activity is modulated by multiple afferents.     

Bilateral projection of the canine tooth pulp to bulbar trigeminal neurons

Unit activity was recorded extracellulary from neurons of the cat medulla following electrical stimulation of the ipsilateral and/or contralateral cannine tooth pulps. The majority of the cells (67%) were only responsive to ipsilateral stimulation. However, many (28%) responded to stimulation of either canine pulp and a few (5%) responsed to contralateral stimulation alone. The neurons were localized histologically in the necleus proprius of the rostral trigeminal nucleus caudalis (NVCaud) and in dorsal portions of the ventromedially contiguous lateral reticular formation (LRF). Cells exclusively responsive to ipsilateral stimuli had a relatively wide dorsoventral distribution. In contrast, 'bilateral' and 'contralateral' cells were situated only in the deep NVCaud-LRF border zone or in immediately adjacent portions of the LRF. Generally, ipsilateral stimuli evoked response bursts with shorter latencies, more spike potentials and briefer interspike intervals than equivalent contralateral stimuli. In experiments designed to study afferent interactions, a conditioning stimulus, applied to either the ipsilateral or the contralateral canine, preceded a test stimulus applied to the other canine at predetermined interstimulus intervals. Responses to the test stimulus were either totally or partially suppressed when intervals of moderate duration (90-500 msec) were used. However, responses to the test stimulus frequently were enhanced when the intervals were breif (less than or equal to 60 msec) or when the teeth were stimulated simultaneously. The results reveal that bilateral afferents from the pulps of the canine teeth converge upon neurons of bulbar trigeminal structures, that the neurons are differentially responsive to the activation of ipsilateral and contralateral pulpal receptors and that bilateral afferent barrages originating in the canine pulps interact to modulate the firing patterns of the neurons.     

Effects of stimulation of the midbrain reticular formation upon thalamo-cortical neurones responsible for cortical recruiting responses

1. In lightly nembutalized cats, effects of high frequency (60-100/sec) repetitive stimulation of the midbrain reticular formation (RF) were tested upon the thalamo-cortical (T-C) neurones which project from the anterior ventral (VA) nucleus of the thalamus and its vicinities to the parietal association cortex and convey impulses responsible for cortical recruiting and spindling-like responses. 2. Tonic maintained or rhythmic grouped firings of the T-C neurones recorded as extracellular units with microelectrode in the thalamus were in the majority suppressed by high frequency RF stimulation during and often for a short time after the stimulation, and they showed later tonic discharges for many seconds or minutes. Intracellular recording from the T-C neurones revealed hyperpolarizing potential changes corresponding to the suppression on high frequency RF stimulation. Field potential analysis in the VA nucleus indicated that the hyperpolarization is ascribed at least in part to IPSPs elicited in the T-C neurones. Responses in some other types of thalamic neurones to the RF stimulation were exemplified to be compared and related with those of the T-C neurones. 3. Desynchronization of the parietal electrocorticogram coincided with the suppression of the T-C neurones and lasted for the time of the later tonic discharges, which contrasted with the rhythmic grouped discharges of the T-C neurones in association with recruiting and spindling-like responses of the cortex. Relations between the thalamo-cortical recruiting system and the ascending reticular activating system were discussed.     

Activation of neurons projecting to the paraventricular hypothalamic nucleus by intravenous lipopolysaccharide

The central nervous system interacts with the immune system to coordinate several components of the acute phase response, although the specific neuroanatomical pathways that mediate these responses are still uncharacterized. However, neurons in both the autonomic and endocrine components of the paraventricular hypothalamic nucleus (PVH) are characteristically activated in different models of immune stimulation. In the current study, we have used intravenous administration of lipopolysaccharide (LPS; 5 or 125 micrograms/kg) to induce the acute phase response. We subsequently coupled immunohistochemistry for Fos (as a marker of neuronal activation) with retrograde transport of the neuroanatomical tracer cholera toxin-b from the PVH. Several of the activated cell groups directly projected to the paraventricular nucleus, including the visceromotor (infralimbic) cortex, median preoptic nucleus, ventromedial preoptic area, bed nucleus of the stria terminalis, parabrachial nucleus, ventrolateral medulla, and nucleus of the solitary tract. These findings indicate that immune system stimulation activates cell groups from multiple nervous system levels that project to the paraventricular nucleus. We hypothesize that the activation of specific autonomic and endocrine elements of the PVH may be due to the activity of distinct afferents that converge on the PVH from multiple components of the central autonomic control system. Our results are consistent with the hypothesis that the PVH plays a key role in integrating diverse physiological cues into the varied manifestations that constitute the cerebral component of the acute phase response.     

A systems analysis approach to medical error

Using decerebrate frogs (Rana catesbeiana), we investigated the role of vagal and laryngeal sensory feedback in controlling motor activation of the larynx. Vagal and laryngeal nerve afferents were activated by electrical stimulation of the intact vagal and laryngeal nerves. Pulmonary afferents were activated by lung inflation. Reflex responses were recorded by measuring efferent activity in the laryngeal branch of the vagus (Xl) and changes in glottal aperture. Two glottic closure reflexes were identified, one evoked by lung inflation or electrical stimulation of the main branch of the vagus (Xm), and the other by electrical stimulation of Xl. Lung inflation evoked a decrementing burst of Xl efferent activity and electrical stimulation of Xm resulted in a brief burst of Xl action potentials. Electrical stimulation of Xl evoked a triphasic mechanical response, an abrupt glottal constriction followed by glottal dilatation followed by a long-lasting glottal constriction. The first phase was inferred to be a direct (nonreflex) response to the stimulus, whereas the second and third represent reflex responses to the activation of laryngeal afferents. Intracellular recordings of membrane potential of vagal motoneurons of lung and nonlung types revealed EPSPs in both types of neurons evoked by stimulation of Xm or Xl, indicating activation of glottal dilator and constrictor motoneurons. In summary, we have identified two novel reflexes producing glottic closure, one stimulated by activation of pulmonary receptors and the other by laryngeal receptors. The former may be part of an inspiratory terminating reflex and the latter may represent an airway protective reflex.     

The distribution of calcium-binding proteins in the lateral geniculate nucleus and visual cortex of a New World monkey, the marmoset, Callithrix jacchus

Antibodies directed against the calcium-binding proteins, parvalbumin and calbindin, can be used to label distinct neuronal subgroups in the primate visual pathway. We analyzed parvalbumin immunoreactivity (P-IR) and calbindin immunoreactivity (C-IR) in the lateral geniculate nucleus (LGN) and visual cortex of the marmoset, Callithrix jacchus. We compared marmosets which were identified as having dichromatic or trichromatic color vision. Within the LGN, the density of P-IR neurones is highest in the parvocellular and magnocellular laminae, but C-IR neurones are found mainly in the koniocellular division of the LGN, that is, the interlaminar zones and S laminae. Not all interlaminar zone cells are C-IR. In the visual cortex, P-IR neurones are present in all laminae except lamina 1, in areas V1 and V2. Neurones which are strongly C-IR are mainly located in laminae 2 and 3 in V1 and V2. Lightly C-IR neurones are concentrated in lamina 4, and are more numerous in V1 than in V2. Quantitative analysis showed no differences in the density or distribution of IR neurones in either LGN or visual cortex when dichromat and trichromat animals were compared. We conclude that this functional difference is not associated with differences in the neurochemistry of calcium-binding proteins in the primary visual pathways.     

Mechanisms of excitation and inhibition in the nigrostriatal system

The extracellular responses of neurones in the neostriatum following single pulse stimulation of the substantia nigra were investigated in urethane anaesthetized rats. Low intensity stimulation (less than 10 V) evoked single large amplitude spikes while higher intensities (10-20 V) elicit a high frequency burst of small amplitude spikes or waves. When spontaneous or glutamate-induced large spikes are recorded, nigral stimulation causes their inhibition coincidentally with the development of a burst. If the burst is prevented, the inhibitory response disappears. Both the nigral evoked inhibition and burst response are unaffected by iontophoretically or systemically administered antonists of dopamine or by chemical lesions of the dopamine-containing nigral neurones. The monosynaptic activation of large amplitude striatal neurones, which could also be identified antidromically by stimulation of the globus pallidus, was reversibly blocked by dopamine antagonists. It is concluded (a) that the burst responses are induced through the antidromic excitation of striatonigral axons within the striatum; (b) that the striatal neurones thus activated are inhibitory interneurones and (c) that the dopamine-containing neurones of the nigra make excitatory synaptic contact with a population of striatal output cells, some of which at least project to the globus pallidus.     

Effect of neuronal NO synthase inhibition on the cerebral vasodilatory response to somatosensory stimulation

Whether nitric oxide (NO) mediates--or not--the local cerebral blood flow (CBF) increases occurring during functional brain activation is still a controversial issue. In the present study, we sought to determine whether neuronal NO synthase is involved in the cerebrovascular response to activation of the trigeminal pathway in the rat. Local CBF was measured using the autoradiographic [14C]iodoantipyrine technique in control alpha-chloralose anesthetized rats and 30 min following administration of 7-nitroindazole (7-NI), an inhibitor of the neuronal NO synthase. Unilateral whiskers stroking increased local CBF in all six regions of the trigeminal pathway. Under 7-NI, CBF was slightly decreased and the vasodilatatory response to whisker stimulation was unaltered in the four trigeminal nuclei studied. In contrast, no significant vasodilatation was noted in the ventral posteromedial thalamic nucleus and somatosensory cortex. These results suggest that the neuronal NO synthase mediates the hyperemia associated with somatosensory activation in second order relay stations but not in the site of termination of primary afferents.     

Cortical hyperexcitability in progressive myoclonus epilepsy: a study with transcranial magnetic stimulation

In progressive myoclonus epilepsy (PME), responses to afferent input are frequently abnormal. It is unclear whether the abnormality lies at the cortical, subcortical, or segmental level. To obtain evidence for an exaggerated effect on motor cortical excitability, we used peripheral nerve and transcranial magnetic stimulation in controls and subjects with idiopathic generalized epilepsy and PME. Mean threshold intensity was higher in those with idiopathic generalized epilepsy and PME than in controls, probably as a result of anticonvulsant treatment. A long-latency response to peripheral stimulation and an exaggerated facilitatory effect of peripheral stimulation on the motor evoked potential was present in subjects with PME. Latency differences between the late responses in the upper and lower limbs provided evidence against a segmental reflex and implicated rapidly conducting fibers in the spinal cord. Both the late response and the facilitatory effect had onset latencies consistent with a transcortical pathway, suggesting an exaggerated effect of afferent input on motor cortical excitability in PME.