Rubrospinal effects on ventral spinocerebellar tract neurones.

Stimulation of the contralateral red nucleus evoked monosynaptic EPSPs in 14 of 82 ventral spinocerebellar tract neurones. In some of these cells the monosynaptic EPSP was followed by a disynaptic IPSP. The remaining cell population received di- or polysynaptic PSPs from the rubrospinal tract, either EPSPs or IPSPs or both. Convergence of the rubrospinal tract onto interneurones of the segmental pathways projecting to VSCT cells was demonstrated. Rubrospinal volleys facilitated disynaptic Ia IPSPs evoked in VSCT neurones from both flexors and extensors, as well as disynaptic Ib IPSPs. Facilitation of the Ia interneurones was disynaptic whereas facilitation of Ib interneurones was monosynaptic. Disynaptic rubrospinal EPSPs and IPSPs were facilitated by volleys in ipsi- as well as in contralateral cutaneous and high threshold muscle afferents. The complex pattern of projections from the rubrospinal tract onto VSCT neurones and the related reflex pathways gives further support to the hypothesis that these tract cells convey information on transmission through interneurones of the spinal segmental mechanisms.     

Effects from the vestibulospinal tract on transmission from primary afferents to ventral spino-cerebellar tract neurones.

Convergence of vestibulospinal and segmental effects onto spinal interneurones which project to the ventral spino-cerebellar tract (VSCT) neurones has been studied by intracellular recording in VSCT cells. The disynaptic Ia IPSPs evoked in a group of VSCT neurones from the quadriceps nerve are monosynaptically facilitated by the vestibulospinal tract while there was no facilitation of Ia IPSP evoked from a flexor nerve. These results support the view that Ia inhibition to VSCT cells and motoneurones is mediated by common interneurones. The disynaptic inhibition evoked in other VSCT cells from the vestibulospinal tract is facilitated by volleys in the contralateral flexor reflex afferents (FRA) or bilaterally from the FRA. It is postulated that these actions are mediated by collaterals of the interneurones responsible for the analogous effects in motoneurones. Findings are reported suggesting that the monosynaptic vestibulospinal EPSP in VSCT cells in most cases is collateral to the excitatory input to the last order interneurones of reflex pathways from the FRA to motoneurones and only exceptionally to the corresponding input to Ia inhibitory interneurones. In many VSCT cells the vestibulospinal tract evoked disynaptic EPSPs which are facilitated from the FRA; the functional significance of this action is uncertain. The results are consistent with the hypothesis that VSCT neurones signal information on interneuronal transmission to motoneurones.     

Tonotopic organization in ventral nucleus of medial geniculate body in the cat

Responses of single units and clusters of units to tone burst stimulation were recorded at 100-micron intervals along vertical electrode penetrations through the medial geniculate bodies of eight barbiturate-anesthetized cats. Marking lesions were placed at two or three locations along most penetrations to aid in histological reconstruction of electrode tracks. Best frequencies and suprathreshold-response latencies were studied at each location along a penetration. The ventral nucleus is physiologically characterized as a region containing narrowly tuned, short-latency (less than or equal to 40 ms) responses and an orderly tonotopic organization. Best frequencies were plotted as a function of depth along single electrode penetrations, and the sequences from different locations in the ventral nucleus were compared. Two-dimensional best-frequency maps were obtained at different rostrocaudal levels. Each map was constructed from best frequencies encountered along several electrode penetrations in the same transverse plane in one brain. We divided the ventral nucleus into seven different rostrocaudal levels, each characterized by a different pattern of tonotopy. Caudolaterally, isofrequency contours parallel the ventrolateral border of the medial geniculate body. At middle levels, low- and mid-frequency contours course ventromedially from the dorsal border of the ventral nucleus toward its medial border, then turn sharply and continue ventrolaterally. Higher-frequency contours parallel this course, but consist of discontinuous dorsal and ventral segments. Rostrally, isofrequency contours are vertically oriented. A model of the three-dimensional tonotopic organization of the ventral nucleus is described that is consistent with the two-dimensional best-frequency maps obtained at different rostrocaudal levels and with locations of ventral nucleus neurons labeled by horseradish peroxidase injections into low-, mid-, and high-frequency representations in auditory cortex. The model includes a planar component and a concentric component. Within the planar component, low frequencies are represented laterally and high frequencies are represented rostromedially. Within the concentric component, low frequencies are represented in a central column that extends mediolaterally through a hole in the mid-frequency representation. The mid-frequency representation in turn is partially surrounded by the high-frequency representation. There is a continuous representation of a "single" frequency in both the planar and concentric components of the model.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ultrastructure of degenerating cerebellothalamic terminals in the ventral medial nucleus of the cat

Summary Terminal degeneration of cerebellar afferents in the ventral medial thalamic nucleus (VM) was studied in cats at the ultrastructural level after uni- or bilateral lesions in the brachium conjunctivum (BC). To achieve discrete lesions within the BC, a new very accurate stereotaxic technique was used. Numerous large terminals belonging to a population of so-called LR boutons were observed degenerating in the VM. The boutons displayed a wide variety of degenerative changes. Some revealed the features of the classical neurofilamentous type of degeneration. Others, although containing a slightly increased number of neurofilaments, featured much more prominently large numbers of coated vesicle shells and heavy accumulations of a flocculent electrondense material. Degeneration in a third group of boutons similar to some extent to the light type of degeneration was characterized by tight clumping of enormously swollen or distorted synaptic vesicles within a light matrix. At later stages, however, all these boutons were believed to become shrunken and electron-dense since intermediate stages between the light- and dark-appearing boutons were observed. The degenerating cerebellar boutons formed asymmetrical synaptic contacts. Groups of 3 or 4 boutons terminated upon dendrites of projection neurons synapsing more frequently on spines than on dendritic stems. The synaptic contacts between cerebellar boutons and the vesicle-containing dendrites of local circuit neurons were encountered as often if not more than the contacts on projection neuron dendrites. Triads consisting of cerebellar boutons and dendrites of both types of neurons were observed very regularly. This synaptic arrangement provides the anatomical basis for the modification of cerebellar input in the VM by interneurons.     

Post-tetanic hyperpolarization produced by an electrogenic pump in dorsal spinocerebellar tract neurones of the cat

1. Hyperpolarization following single and repetitive excitation of dorsal spinocerebellar tract (DSCT) neurones of the cat was studied by intracellular recording.2. Hyperpolarization following an antidromic action potential consisted of an initial, brief phase (undershoot) and a late, prolonged phase. The latter hyperpolarization was independent of the membrane potential, whereas the former was reversed in polarity by hyperpolarizing pulses applied across the DSCT cell membrane.3. DSCT neurones showed a prolonged hyperpolarization after a train of antidromic action potentials. The amplitude and duration of the hyperpolarization were dependent on the number and the frequency of action potentials. A similar hyperpolarization was observed following a train of impulses evoked by depolarizing pulses applied through the intracellular electrode.4. There was no detectable conductance change during the post-tetanic hyperpolarization. The latter showed no reversal potential when the membrane potential was altered.5. The half-decay time of the post-tetanic hyperpolarization was lengthened when the cord temperature was lowered. The temperature coefficient (Q(10)) was 2.4 within the range of 31-40 degrees C.6. The amplitude of the undershoot following each action potential was assumed to provide a criterion for the accumulation of the extracellular K(+). Alterations in the amplitude of undershoots during repetitive excitation suggested that the duration of post-tetanic hyperpolarization depends on the accumulation of extracellular K(+) as well as of intracellular Na(+) associated with a train of impulses.7. It is suggested that post-tetanic hyperpolarization is produced by an electrogenic sodium pump. A possible significance of such a hyperpolarization in impulse coding is discussed.     

Molecular mechanisms in the formation of the medial longitudinal fascicle

The first neurons in the vertebrate brain form a stereotypical array of longitudinal and transversal axon tracts, the early axon scaffold. This scaffold is thought to lay down the basic structure for the later, more complex neuronal pathways in the brain. The ventral longitudinal tract is pioneered by neurons located at the ventral midbrain-forebrain boundary, which form the medial longitudinal fascicle. Recent studies have shed some light on the molecular mechanisms that control the development of the medial longitudinal fascicle. Here, we show that patterning molecules, notably the ventralizing signalling molecule Shh, are involved in the formation of medial longitudinal fascicle neurons and in medial longitudinal fascicle axon guidance. Downstream of Shh, several homeobox genes are expressed in the tegmentum. We describe the expression patterns of Sax1, Emx2, Six3, Nkx2.2 and Pax6 in the mesencephalon and pretectum in detail. Furthermore, we review the evidence of their molecular interactions, and their involvement in neuronal fate specification. In particular, Sax1 plays a major role in fate determination of medial longitudinal fascicle neurons. Finally, we discuss the available data on axon guidance mechanisms for the medial longitudinal fascicle, which suggest that different guidance molecules such as class 3 Semaphorins, Slits and Netrins act to determine the caudal and ventral course of the medial longitudinal fascicle axons.     

Neck muscle afferent input to spinocerebellar tract cells of the central cervical nucleus in the cat

Summary Extracellular and intracellular recordings were made from spinocerebellar tract neurones of the central cervical nucleus (CCN) in C1–C3 segments of the anaesthetized cat. These neurones were identified by antidromic activation from the cerebellar peduncle. Stimulation of the ipsilateral dorsal root elicited extracellular spikes or EPSPs with a monosynaptic latency in almost all CCN neurones in the same segment (segmental input). Late excitatory effects were also observed in about one third of CCN neurones. The monosynaptic EPSP was occasionally followed by an IPSP. The excitatory input from the dorsal root to CCN neurones was extended over several segments for some CCN neurons (extrasegmental input). Monosynaptic excitation was evoked in CCN neurones after stimulation of dorsal neck muscle nerves as well; i.e. splenius (SPL), biventer cervicis and complexus (BCC), rectus capitus dorsalis, and obliquus capitus caudalis. Thresholds for this excitation were near the threshold of the nerve, suggesting that it originated from group I fibres. The component of excitation added after strong stimulation of neck muscle nerves would be attributed to group II fibres. When a CCN neurone received excitatory input from the nerve of one muscle, it was generally not affected by stimulation of other nerves in the same segment. Such muscle specificity of segmental input was the principal pattern of connexion of neck muscle afferents with CCN neurones. In some cases, however, excitatory convergence from SPL and BCC nerves onto single CCN neurones or excitation from the SPL nerve and inhibition from the BCC nerve were also observed. Nearly half of the CCN neurones received input from one muscle nerve of the same segment and not from the afferent of the same muscle of different segments, indicating a segment specificity of input. In the remaining CCN neurones, weaker excitatory effects were induced from afferents of different segments as well. In such extrasegmental effects, inputs to CCN neurones from caudal segments predominated in frequency over those from rostral segments. The origin of extrasegmental input was generally confined to the same muscle. Low threshold muscle afferents from the SPL and BCC were intraaxonally stained with HRP. The collaterals of the stained fibre distributed branchlets and terminals to the CCN, laminae VII, VIII, and motor nuclei. Two fibres responding to local muscle prodding or stretch showed a similar morphology. The findings indicated that muscle spindle afferents from primary endings projected to the CCN.Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan     

Morphology of physiologically characterized medial lemniscal axons terminating in cat ventral posterior thalamic nucleus

1. Medial lemniscal axons were identified by extra- and intracellular recording in the thalamic ventral posterior lateral nucleus (VPL) of cats and injected intracellularly with horseradish peroxidase (HRP). 2. Axons were characterized in terms of their latencies of response to stimulation of the medial lemniscus in the medulla, their receptive fields, and the temporal patterns of their discharge in response to stimulation of the receptive field with natural, hand-held stimuli. One-hundred sixty-six axons were placed in five operational groups: hair transient (Ht) (n = 41); hair sustained (Hs) (n = 45); pressure transient (Pt) (n = 14); pressure sustained (Ps) (n = 27), and deep or joint (Jt) (n = 39). 3. There was a tendency for Jt axons to have their terminations in anterodorsal parts of VPL and for those in the four cutaneous categories to have theirs in more central parts of the nucleus. 4. Nineteen injected axons with receptive fields mainly on the distal forelimb were subjected to detailed morphological analysis in terms of extent of terminal field and number of boutons. All axons ended in localized terminal fields that were more extensive anteroposteriorly than in the other dimensions. All showed an overall similarity and similar ranges of variation. There was a tendency, however, for Jt axons to have the least extensive terminations with fewest boutons. Ps axons had the most extensive terminations and largest number of boutons; Hs axons had small terminations and few boutons but Ht axons had small-to-medium arborizations with many boutons; no Pt axons were sufficiently well stained to enable comparisons of them with the others. There were no marked differences in axon diameter or conduction velocity among the five types. 5. Boutons identified light microscopically tended to be clustered in linear chains along proximal dendrites of relay neurons and electron microscopy revealed that they were terminals making synaptic contacts on relay cell dendrites and on presynaptic dendrites of interneurons. 6. These results reveal more similarities than differences among lemniscal axon terminations in VPL. Further studies of a quantitative nature on stimulus-response coupling and on the geographic distribution of lemniscal synapses on relay neurons will be required to reveal how lemniscal input is translated into relay cell output in VPL.     

The morphology of spinocervical tract neurones in the cat.

1. The morphology of physiologically identified spinocervical tract (SCT) neurones was studied using the intracellular injection of Procion dyes in anesthetized and decerebrate cats. 2. Extracellular recordings were made from SCT neurones at depths between 1000 and 2850 mum from the cord surface but neurones were only stained at depths between 1100 and 2400 mum. 3. The dendritic trees of stained SCT neurones were reconstructed in the transverse plane of the spinal cord. All SCT neurones had well developed dorsal dendrites but despite this it is not possible to consider the twenty-two SCT cells in out sample as consituting a morphologically homogenous population. 4. There was no correlation between the form of the dendritic trees and the depth of SCT neurones in the dorsal horn as determined both from measurements from the dorsal grey-white border and the position of cells with respect to the border between Rexed's laminae II and III. 5. Six types of SCT neurones were identified on the basis of the form of their dendritic trees as viewed in the transverse plane: (1) radially symmetrical, (2) semicircular, (3) large elliptical, (4) bilobed, (5) triangular, (6) small elliptical. Each of these types was found only in a certain region across the dorsal horn although any one region could contain more than one type. 6. Spinocervical tract neurones with small elliptical dendritic trees always had receptive fields encompassing part of the hip or thigh and were unique in being located in the lateral portions of the horn. 7. There was no correlation between the morphology of SCT neurones and their excitatory cutaneous inputs, receptive field size, axonal conduction velocity or depth in the dorsal horn.     

Action and specificity of ventral medullary vasopressor neurones in the cat

An investigation has been made into the mode and specificity of action of ventral medullary pressor neurones. These were activated by microinjections of excitant amino acid into the ventral brain surface of chloralose-anaesthetized, artificially ventilated cats, and a number of autonomic responses were measured. Indirect assessment of cardiac output (by CO2 delivery to the lungs) suggested that it was either unchanged or fell during pressor responses. The inference that activating the pressor neurones caused vasoconstriction was confirmed directly for hindlimb and mesenteric vascular beds, by a rise in inflow pressure when they were perfused at constant flow. Sympathetic activity also increased in cervical, splanchnic and inferior cardiac nerves. Bradycardia often (but not always) accompanied pressor responses, but this was abolished by vagotomy, although not by cutting the sinus and aortic nerves. In vagotomized cats, tachycardia could be produced during pressor responses even after either bilateral adrenalectomy or removal of the stellate ganglia, indicating both direct sympathetic drive to the heart and release of adrenal catecholamines. Plasma adrenaline levels were measured and found to increase by up to 20.2 times control values, plasma noradrenaline up to 12.6 times, and dopamine by a smaller amount. Activating ventral medullary pressor neurones appeared to have no significant action on pupils, nictitating membranes or piloerection. In three adrenalectomized, vagotomized cats, only small, inconsistent effects were measured on intestinal motility following pressor neurone excitation. However, large electrodermal responses could be evoked from the ventral medulla, but from a distinct area medial to the pressor neurones.(ABSTRACT TRUNCATED AT 250 WORDS)     

Responses of fastigial nucleus neurones to stimulation of the caudate nucleus in the cat.

1. Extracellular records were made of single unit activity evoked in the fastigial nucleus (FN) by electrical stimulation of the caudate nucleus (CN) in cats anaesthetized with sodium thiopentone. 2. Single shock stimulation evoked bilaterally complex responses having up to three components. These were, in temporal order, with percent of units exhibiting them, (a) a short burst of evoked spikes with either a latency of smaller than 5-5 msec and no associated field potential (6 percent) or a latency of 7-5-20 msec and associated with a prominent negative-going field potential (36 percent); (b) suppression of spontaneous discharges for a period of 20-150 msec (90 percent); (c) a resumption of spike discharges with a transient increase in frequency lasting for 25-500 msec (66 percent). 3. Changes in component (c) of the response patterns of some units were noted during repetitive stimulation The nature of the change depended on the laterality of the FN with respect to the stimulated CN. 4. Mechanisms which might account for the responses are discussed, but it is emphasized that some of the results cannot yet be satisfactorily explained.     

Substance P-immunoreactive and serotonin-containing neurones in the ventral brainstem of the cat

Substance P-like immunoreactive cell bodies have been described in the cat brainstem after local injections of colchicine. Substance P-containing neurons were found in the nucleus raphe pallidus, the nucleus raphe obscurus and at the caudal end of the nucleus raphe magnus. Two groups of substance P-positive (+) cells were also found in the ventrolateral medulla. Small substance P+ cells were present in a narrow band immediately ventral to the facial nucleus, and a second group of small and medium sized neurones was found in a strip ventrolateral to the rostral half of the inferior olive. Some of these cells lay in close proximity to the ventral surface of the brain. Double labelling studies indicated that within the raphe nuclei many substance P+ neurones also contained serotonin, while within ventrolateral areas of the medulla, the most rostral cell group stained only for substance P and the more caudal nucleus for both substance P and serotonin.     

Inhibition from nucleus raphe magnus of tooth pulp responses in medial reticular neurones of the cat can be antagonized by bicuculline

In decerebrate cats stimulation in nucleus raphe magnus (NRM) inhibited the response of neurones in the medial brain stem reticular formation to electrical stimulation of the tooth pulp. These evoked responses were also reduced by iontophoretically applied GABA. The inhibition from NRM was blocked by bicuculline applied by iontophoresis in 10 out of 16 neurones and the actions of GABA were also antagonized. Inhibition following stimulation in the contralateral reticular formation was not blocked by bicuculline. The results suggest that GABA is involved as a neurotransmitter in mediating the effects of NRM stimulation on reticular neurones.     

Pattern of pyramidal tract collateralization to medial thalamus,lateral hypothalamus and red nucleus in the cat

Summary Stimulating electrodes were placed in the red nucleus, lateral hypothalamus and medial thalamus in order to determine whether pyramidal tract (PT) neurons send collaterals to those sites. The red nucleus projections are well-known, but it was discovered that PT neurons also project into the other two sites. All of the fibers that sent collaterals to all three sites originated from fast PT neurons. Those that responded to stimulation of the skin and that sent collaterals to two or three sites were predominantly fast PT neurons. Those neurons that responded only to cerebral peduncle stimulation were predominantly slowly-conducting, when compared with the set of PT neurons in response to cerebral peduncle stimulation. The patterns of collateral branching to red nucleus and to lateral hypothalamus were similar, suggestimg a similar synaptic effect of the pyramidal system in the two sites. Measurement of the speed of conduction from three sites along the length of corticospinal fibers revealed large changes on some, but not all, fibers; there was no evident pattern to these changes that might be associated with collateral branching. A new hypothesis concerning the functional role of fast PT neurons in regulating movement is presented.Dr. Canedo was supported by a Fogarty International Research Fellowship