Contralateral Interstitial Nucleus Of Cajal Research Articles

Ocular Tilt Reaction in Compensated Vestibular Schwannoma

Ocular Tilt Reaction in Compensated Vestibular Schwannoma

Input-output organization of inhibitory neurons in the interstitial nucleus of Cajal projecting to the contralateral trochlear and oculomotor nucleus

Neurons in the interstitial nucleus of Cajal (INC) that are known to be involved in eye and head movements are excitatory. We investigated the input-output organization of inhibitory INC neurons involved in controlling vertical saccades. Intracellular recordings were made in INC neurons activated antidromically by stimulation of the contralateral trochlear or oculomotor nucleus, and their synaptic input properties from the superior colliculi (SCs) and the contralateral INC were analyzed in anesthetized cats. Many INC neurons projected to the contralateral trochlear nucleus, Forel's field H, INC, and oculomotor nucleus, and mainly received monosynaptic excitation followed by disynaptic inhibition from the ipsi- and contralateral SCs. After sectioning the commissural connections between the SCs, these neurons received monosynaptic excitation from the ipsilateral medial SC and disynaptic inhibition via the INC from the contralateral lateral SC. Another group of INC neurons were antidromically activated from the contralateral oculomotor nucleus, INC and Forel's field H, but not from the trochlear nucleus, and received monosynaptic excitation from the ipsilateral lateral SC and disynaptic inhibition from the contralateral medial SC. The former group was considered to inhibit contralateral trochlear and inferior rectus motoneurons in upward saccades, whereas the latter was considered to inhibit contralateral superior rectus and inferior oblique motoneurons in downward saccades. The mutual inhibition existed between these two groups of INC neurons for upward saccades on one side and downward saccades on the other. This pattern of input-output organization of inhibitory INC neurons suggests that the basic neural circuits for horizontal and vertical saccades are similar.

Neural Organization of the Pathways From the Superior Colliculus to Trochlear Motoneurons

The neural organization of the pathways from the superior colliculus (SC) to trochlear motoneurons was analyzed in anesthetized cats using intracellular recording and transneuronal labeling techniques. Stimulation of the ipsilateral or contralateral SC evoked excitation and inhibition in trochlear motoneurons with latencies of 1.1-2.3 and 1.1-3.8 ms, respectively, suggesting that the earliest components of excitation and inhibition were disynaptic. A midline section between the two SCs revealed that ipsi- and contralateral SC stimulation evoked disynaptic excitation and inhibition in trochlear motoneurons, respectively. Premotor neurons labeled transneuronally after application of wheat germ agglutinin-conjugated horseradish peroxidase into the trochlear nerve were mainly distributed ipsilaterally in the Forel's field H (FFH) and bilaterally in the interstitial nucleus of Cajal (INC). Consequently, we investigated these two likely intermediaries between the SC and trochlear nucleus electrophysiologically. Stimulation of the FFH evoked ipsilateral mono- and disynaptic excitation and contralateral disynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the ipsilateral SC facilitated FFH-evoked monosynaptic excitation. Stimulation of the INC evoked ipsilateral monosynaptic excitation and inhibition, and contralateral monosynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the contralateral SC facilitated contralateral INC-evoked monosynaptic inhibition. These results revealed a reciprocal input pattern from the SCs to vertical ocular motoneurons in the saccadic system; trochlear motoneurons received disynaptic excitation from the ipsilateral SC via ipsilateral FFH neurons and disynaptic inhibition from the contralateral SC via contralateral INC neurons. These inhibitory INC neurons were considered to be a counterpart of inhibitory burst neurons in the horizontal saccadic system.

Neural Pathways for Vertical Saccades: From the Superior Colliculus to Trochlear Motoneurons

The pathways from the superior colliculus (SC) to vertical ocular motoneurons were analyzed in anesthetized cats using intracellular recording from trochlear motoneurons. Electrical stimulation of the ipsilateral or contralateral SC evoked disynaptic excitation and inhibition in trochlear motoneurons. Stimulation of the ipsilateral Forel's field H (FFH) and the contralateral interstitial nucleus of Cajal (INC) evoked monosynaptic excitation and inhibition in trochlear motoneurons, respectively. Preconditioning stimulation of the SC facilitated FFH-evoked monosynaptic excitation. The results showed that trochlear motoneurons receive disynaptic excitation via the FFH from the ipsilateral SC and disynaptic inhibition via the INC from the contralateral SC.

Tonic contraversive ocular tilt reaction due to unilateral meso‐diencephalic lesion

We studied 4 patients with tonic contraversive ocular tilt reactions due to unilateral, paramedian, mesodiencephalic lesions. This is in contrast to the only 2 previously reported patients with ocular tilt reactions due to unilateral mesodiencephalic lesions, each of whom had a paroxysmal ipsiversive ocular tilt reaction. This new finding is considered in the context of previous clinical and experimental data on the various types of ocular tilt reactions that follow stimulation or destruction of the peripheral and central vestibular system. Otolithic inputs to the interstitial nucleus of Cajal from the contralateral vestibular nucleus and motor outputs from the interstitial nucleus of Cajal to cervical and ocular motoneurons could be involved in the ocular tilt reaction. We propose that in patients with unilateral meso-diencephalic lesions, a tonic contraversive ocular tilt reaction could be due to persistently decreased resting activity of ipsilateral interstitial nucleus neurons, whereas a paroxysmal ipsiversive ocular tilt reaction could be due to transiently increased activity of the same interstitial nucleus neurons. Cases of ocular tilt reaction due to unilateral meso-diencephalic lesion point to the existence of a crossed graviceptive pathway between the vestibular nucleus and the contralateral interstitial nucleus of Cajal.

Mesodiencephalic projections to the vestibular complex in the cat.

The distribution of cells in the rostral medial mesencephalon and caudal diencephalon which project to the vestibular complex was mapped in the cat by using retrograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Subsequent experiments using anterograde transport of WGA-HRP clarified the position of the terminations of the mesodiencephalic-derived afferents in the vestibular complex. After large injections which involved the entire vestibular complex, retrogradely labeled cells were seen in both the ipsilateral and contralateral interstitial nucleus of Cajal (INC) and were more numerous in its rostral pole. Labeled cells also occurred in the perifascicular region, both immediately adjacent to the fasciculus retroflexus and rostroventral to it. Fusiform midline cells of the Edinger-Westphal nucleus were also labeled, as well as a number of cells in the adjacent somatic portion of the oculomotor complex (OMC). Another group of labeled cells was observed within the contralateral medial terminal nucleus of the accessory optic tract (MTN) and in the posterior hypothalamic nucleus. Injections limited to subregions of the vestibular complex resulted in similar but slightly varying distributions and numbers of retrogradely labeled cells. After injections covering the caudal half of the medial vestibular nucleus (MVN) and descending vestibular nucleus (DVN), labeled cells in the INC and tegmentum dorsal to it were especially prominent, but none was seen in the MTN or OMC. Injections placed in the rostral MVN, lateral vestibular nucleus, y group, and superior vestibular nucleus resulted in a distribution of labeled cells similar to that seen following global vestibular injections, but these cells were fewer in number. After an injection confined to the y group, a small number of retrogradely labeled cells were seen in the rostral pole of the INC and immediately ventral to the fasciculus retroflexus. Projections from the rostral medial mesencephalon and caudal diencephalon to the MVN, DVN, and y group were confirmed by using anterograde transport of WGA-HRP. Direct projections from the INC-perifascicular regions and somatic neurons of the OMC to the caudal vestibular complex could play a role in eye-head coordination. Those projections from the rostral INC and MTN to the rostral vestibular complex may play a role in vertical eye movements and responses to visual stimuli which move in the vertical plane.

Projections of the group y of the vestibular nuclei and the dentate and fastigial nuclei of the cerebellum to the interstitial nucleus of Cajal

Experiments were performed to study the projection of the group y of the vestibular nuclei and the dentate and fastigial nuclei of the cerebellum to the interstitial nucleus of Cajal (INC) in cats by using retrograde axonal transport of horseradish peroxidase (HRP) and electrophysiological methods; and to study the vestibular responses of such projection neurons. Following injections of HRP into the unilateral INC, with partial involvement of the surrounding reticular formation, including the nucleus of Darkschewitsch (ND), many retrogradely labeled neurons were found in the dorsal part of the group y nucleus contralateral to the injection site. Labeled cells were also seen in the contralateral dentate nucleus, frequently in its caudal-ventral part, and in the contralateral fastigial nucleus at all rostrocaudal levels, but most frequently in its caudal part. In electrophysiological experiments performed on cats anesthetized with α-chloralose or N 2O and paralyzed with gallamine, group y, dentate and fastigial nuclei neurons were antidromically activated by weak stimuli that were confined to the contralateral INC. Depth-threshold curves for antidromic activation of such neurons revealed that the lowest threshold points were within the INC, but not in the ND. The INC-projecting neurons in the group y and dentate nuclei did not respond to electrical stimulation of the ipsilateral or contralateral vestibular nerve, indicating that they do not receive direct labyrinthine inputs. On the contrary, many fastigial neurons projecting to the INC responded to labyrinthine stimulation, suggesting that they may be involved in the vestibular reflexes. These results suggest a difference in properties of INC-projecting neurons in these nuclei.

Connections and oculomotor projections of the superior vestibular nucleus and cell group ‘y’

Attempts were made to determine brainstem and cerebellar afferent and efferent projections of the superior vestibular nucleus (SVN) and cell group ‘y’ (‘y’) in the cat using axoplasmic tracers. Injections of HRP, WGA-HRP and [ 3H]amino acids were made into SVN and ‘y’ using two different infratentorial stereotaxic approaches. Controls were provided by unilateral HRP injections involving the oculomotor nuclear complex (OMC), the interstitial nucleus of Cajal (INC) and the deep cerebellar nuclei (DCN). Large injections of SVN almost invariably involved ‘y’ and dorsal parts of the lateral vestibular nucleus (LVN). Smaller injections involved central and ventral peripheral parts of SVN. Discrete injections of ‘y’ involved small dorsal parts of LVN. Afferents to SVN are derived mainly from the vestibular nuclei (VN) and parts of the vestibulocerebellum. SVN receives afferents: (1) bilaterally from caudal portions of the medial (MVN) and inferior (IVN) vestibular nuclei and ‘y’; (2) contralaterally from ventral and lateral parts of SVN and rostral MVN; and (3) ipsilaterally from the nodulus, uvula and medial parts of the flocculus. Purkinje cells (PC) in medial parts of the flocculus project to central regions of SVN, while PC in the nodulus and uvula appear to project mainly to dorsal peripheral regions of SVN. SVN receives sparse projections from the ipsilateral INC, the contralateral central cervical nucleus (CCN) and virtually no projections from the reticular formation. SVN projects via the medial longitudinal fasciculus (MLF) to the ipsilateral trochlear nucleus (TN), the inferior rectus subdivision of the OMC, the INC, the nucleus of Darkschewitsch (ND) and the rostral interstitial nucleus of the MLF (RiMLF). Contralateral projections of SVN cross in the ventral tegmentum caudal to most of the decussating fibers of the superior cerebellar peduncle and terminate in the dorsal rim of the TN and the superior rectus and inferior oblique subdivisions of the OMC; sparse crossed projections enter the INC and the ND. Cerebellar projections of SVN end as mossy fibers in the ipsilateral nodulus, uvula and in medial parts of the flocculus bilaterally. Retrograde transport from unilateral injections of the OMC indicate that afferents from SVN arise ipsilaterally from central and dorsal regions and contralaterally from dorsal peripheral regions. Ventral cell group ‘y’ receives small numbers of afferent fibers from caudal central parts of the ipsilateral flocculus. No fibers from ventral ‘y’ could be traced to other vestibular nuclei, the OMC or the cerebellum. Retrograde transport from unilateral injections of the OMC indicate that afferents arise mainly from dorsal ‘y’ with strong contralteral dominance. The DCN have no projection to the OMC, although some cells in the ventral dentate nucleus project to the region of contralateral INC.

Effects of lesion of the interstitial nucleus of Cajal on vestibular horizontal canal neurons in the cat.

Effects of procaine infusion into the interstitial nucleus of Cajal (INC) on vestibular nuclear neurons related to the horizontal canal were studied in cats anesthetized with nitrous oxide and paralyzed with gallamine. Neurons that responded to sinusoidal horizontal rotation (at 0.18 Hz) were recorded extracellularly in the medial and descending vestibular nuclei. Spontaneous activity of type I neurons increased, whereas that of type II neurons decreased following procaine infusion into the ipsilateral INC. Gain of the neuronal response to horizontal rotation decreased after the ipsilateral INC infusion, but there was no consistent effect on phase. Infusion into the contralateral INC seemed less effective. Similar effects were obtained with electrolytic lesions that were confined to the ipsilateral INC area. These results suggest that the INC influences type I neurons through inhibitory action of type II neurons and that it eventually controls the gain, but not the phase, of the horizontal vestibular reflexes.

Projections of medial terminal accessory optic nucleus, ventral tegmental nuclei, and substantia nigra of rabbit and rat as studied by retrograde axonal transport of horseradish peroxidase.

Projections of the medial terminal nucleus (MTN) of the accessory optic system, the ventral tegmental area of Tsai, and the substantia nigra of the rabbit and the rat have been studied by the method of retrograde axonal transport of horseradish peroxidase. The data show that MTN projections are remarkably similar in the rabbit and rat. The MTN projects heavily to the ipsilateral nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system and to a portion of the contralateral ventral tegmental area of Tsai that we have termed the visual tegmental relay zone (VTRZ). Further, the MTN sends projections to the ipsilateral mesencephalic (deep mesencephalic nucleus, pars medialis) and pontine (nucleus reticularis pontis oralis) reticular formations; the contralateral dorsolateral division of the basal pontine complex; the superior and lateral vestibular nuclei (contralateral in rat; bilateral in rabbit); and the ipsi- and contralateral interstitial nucleus of Cajal, nucleus of Darkschewitsch, and supraoculomotor-periaqueductal gray. The findings also indicate that the MTN has a small bilateral, but mainly ipsilateral, projection to the dorsal cap, its ventrolateral outgrowth, and the B division of the inferior olivary complex. This study further reveals that ventral tegmental nuclei (n. parabrachialis pigmentosus and n. paranigralis) and subdivisions of the substantia nigra (pars compacta and pars reticulata) project to many brain stem targets of the MTN. Thus, the VTRZ projections are similar to those of the MTN in both distribution and density except that the VTRZ projection to the inferior olive is substantially stronger. The nucleus parabrachialis pigmentosus sends a small contralateral projection to the VTRZ and a moderate-sized bilateral projection to the supraoculomotor-periaqueductal gray. The nucleus paranigralis sends a moderate number of axons to the ipsilateral deep mesencephalic nucleus, pars medialis, and the nucleus reticularis pontis oralis and provides a strong bilateral projection to the supraoculomotor-periaqueductal gray. The pars compacta of the substantia nigra provides a sparse input to the ipsilateral deep mesencephalic nucleus, pars medialis, and nucleus reticularis pontis oralis, and to the contralateral VTRZ and sends a moderate number of axons, bilaterally, to the supraoculomotor-periaqueductal gray. The pars reticulata of the substantia nigra sends an ipsiateral projection of moderate size to the intermediate and deep layers of the superior colliculus, sparse ipsilateral projections to the deep mesencephalic nucleus, pars medialis, and nucleus reticularis pontis oralis, and a sparse bilateral projection to

Interstitial nucleus of Cajal (INC) projections to the region of Probst's tract

These studies were designed to investigate projections of the interstitial nucleus of Cajal (INC) to the region of the contralateral Probst's tract (PrTr). In electrophysiological experiments, INC neurons were antidromically activated from the contralateral PrTr, the medial longitudinal fasciculus (MLF) at medullary levels and the MLF at spinal cord levels. Some INC cells could be antidromically activated only from PrTr and others from both PrTr and the MLF. Anatomical experiments confirmed the existence of an INC projection into the region of the contralateral PrTr. Following injections of fluorescent dyes into the PrTr area, retrogradely labeled neurons were observed in the contralateral INC, with only occasional labeling ipsilaterally. Injections which included the medial vestibular nucleus labeled a greater number of INC cells ipsilaterally. After injections of dyes into the medullary MLF, retrogradely labeled cells were observed bilaterally in INC, although in greater numbers ipsilaterally. In experiments in which different dyes were injected into PrTr and the MLF, double labeled cells were found in the contralateral INC.

Responses of vestibular neurons to stimulation of the interstitial nucleus of Cajal in the cat.

(1) Spikes of neurons in the medial and descending vestibular nuclei were recorded extracellularly and their responses to stimulation of the interstitial nucleus of Cajal (INC) were studied in cerebellectomized cats under chloralose anesthesia. Stimuli applied in the ipsilateral INC excited 37% of neurons that did not exhibit spontaneous activity. About 84% of spontaneously discharging neurons were influenced by the INC; typical responses were excitation (35%), inhibition (22%) and excitation followed by inhibition (27%). Of the neurons that were excited, 24% fired monosynaptically. Such monosynaptic activation was evoked by stimulating the INC and midbrain medial longitudinal fasciculus (MLF), but was not evoked by stimulating the lateral midbrain reticular formation. Polysynaptic excitation or inhibition was evoked more widely, but the lowest threshold points were within the INC. Stimulation of the contralateral INC also evoked polysynaptic excitation or inhibition. However, the frequency of occurrence of the evoked responses was significantly smaller compared to the ipsilateral responses. (2) Intracellular recordings revealed that some medial and lateral vestibular neurons received monosynaptic excitatory postsynaptic potentials (EPSPs), others received polysynaptic EPSPs or inhibitory postsynaptic potentials (IPSPs) from the ipsilateral INC. The minimum latency for the IPSPs suggests that the pathway is at least disynaptic. No significant collision was observed between monosynaptic EPSPs evoked by the ipsilateral INC and contralateral vestibular nuclei. Acute lesions that damaged the pontine MLF and part of the reticular formation did not abolish monosynaptic responses of vestibular neurons by the INC. Depth threshold curves for mono- or polysynaptic responses drawn before and after the lesions were virtually similar. Antidromic thresholds of interstitio-vestibular fibers evoked from the pontine MLF showed that a great majority of these fibers run outside the MLF at the pontine level. These results control for vestibular axon reflexes, since vestibulo-interstitial fibers ascend within the MLF (cf. Gacek 1971). (3) Responses to stimulation of the INC were not different among different types of canal responding neurons; vertical and horizontal canal responding neurons received similar effects. However, canal responding neurons that received excitation from the contralateral vestibular nerve were activated more frequently by the INC than those that received inhibition (χ2 test, p<0.01). Qualitatively similar results were obtained from vestibular neurons that had different projection sites; vestibulospinal, contralateral INC-projecting and contralateral vestibular nuclei-projecting neurons received similar effects. (4) Vestibulo-collic reflexes, studied with EMG, were modified by preceding INC stimulation. Intracellular recordings from some neck motoneurons showed that disynaptic EPSPs evoked by stimulation of the contralateral vestibular nerve were modified by preceding INC stimulation applied ipsilateral to the stimulated vestibular nerve. INC stimulation alone did not evoke any response in these motoneurons, suggesting that the interaction of the labyrinthine and interstitial effects occurred at least in part at the vestibular nuclei. (5) Some medial and descending vestibular neurons showed multiple branching, projecting to the contralateral INC, C1 or contralateral vestibular nuclei. About 34% of neurons that projected to the contralateral INC were also antidromically activated from the C1; some of them received vertical canal inputs.

Vestibular responses and branching of interstitiospinal neurons.

1. Interstitiospinal neurons were activated by antidromic stimulation of the ventromedial funiculus of the spinal cord at C1 and C4 in cerebellectomized cats under chloralose anesthesia. 46% of these neurons responded only at C1 (N cells) and the remaining 54% responded at C4 also (D cells). There is no topographical difference in the location of N and D cells. Conduction velocities of N cells were significantly slower than those of D cells. 2. Stimulation of the contralateral whole vestibular nerve evoked firing of 31% of both N and D cells; some responded early enough to suggest disynaptic connections, many responded late. Stimulation of the ipsilateral whole vestibular nerve evoked firing of several cells, one spontaneously discharging D cell was inhibited. 3. Stimulation of the contralateral individual semicircular canal nerves evoked firing of 33% of N cells and 13% of D cells. Most of these responses were late. N cells responded not only to the vertical canals but also to the horizontal canal, whereas D cells responded to the horizontal canal, but seldom to the vertical ones. Most canal responding neurons received specific input, only two N cells received convergent input from both the anterior and horizontal canals. Stimulation of the ipsilateral canals did not evoke excitation of any cells tested; one D cell was inhibited by stimulation of the horizontal canal nerve. 4. Stimulation of the rostral medial vestibular nucleus evoked characteristic negative field potentials centered in the contralateral interstitial nucleus of Cajal (INC). Approximately 60% of both N and D cells received excitation from the contralateral vestibular nuclei. About 17% of these responding neurons received monosynaptic excitation, most frequently from the rostral medial nucleus. Stimulation of the ipsilateral vestibular nuclei evoked firing of 12% of both N and D cells. 5. Twenty-nine neurons were fired antidromically by weak stimuli applied to the ipsilateral vestibular nuclei. Twenty-seven of the 29 were activated only from C1 and were found in the INC (10 cells) and in the reticular formation dorsal to the INC (19 cells). Measurement of the spread of the effect of stimulus current and comparison of latencies to stimulation of the vestibular nuclei and C1 indicated that these neurons have axon collaterals going to the ipsilateral vestibular nuclei. Only one of them received excitation from the contralateral posterior canal, others did not respond to the labyrinth. Some were activated by stimulation of the vestibular nuclei.

Interstitiospinal action on forelimb, hindlimb, and back motoneurons.

Responses of motoneurons supplying muscles of the forelimbs, hindlimbs, and back to stimulation of the interstitial nucleus of Cajal (INC) were recorded intracellularly in cats under chloralose anesthesia. Stimulation of the ipsilateral and contralateral INC evoked predominantly excitatory postsynaptic potentials in these motoneurons. Response latencies and properties of responses to multiple shock stimuli indicated that the responses were evoked by a di- or polysynaptic pathway. Stimulation of the anterior MLF (P2), which should have activated the entire interstitiospinal tract, but few reticulospinal or vestibulospinal fibers, evoked only polysynaptic responses. These results indicate that the INC does not establish direct synaptic connections with limb and back motoneurons.

Oculomotor nucleus afferents in the monkey demonstrated with horseradish peroxidase

The afferents to the oculomotor nucleus were examined in the macaque monkey by means of horseradish peroxidase. The demonstration of afferents from the contralateral interstitial nucleus of Cajal, and from the nearby rostral interstitial nucleus of the medial longitudinal fasciculus, predominantly ipsilateral to the injection site, confirms the significant role of these two regions as premotor structures. HRP label in the pretectal area was strictly confined to the olivary nucleus and the corresponding pathway seems to concern the Edinger-Westphal nucleus in particular. A purely crossed internuclear pathway emanating from the abducens nucleus could be established, and evidence for the presence of intranuclear connections within the oculomotor complex itself was found. Ipsilateral afferents from the superior vestibular nucleus and bilateral connections from the medial vestibular nucleus and the y-group were prominent. A projection, showing some rostrocaudal organization within the oculomotor nucleus, arises from the ipsilateral perihypoglossal complex, and other afferents originated from the underlying medullary reticular formation. No evidence was found for the existence of afferents from the paramedian pontine reticular formation, the nucleus Darkschewitsch, the nuclei of the posterior commissure, the lateral tegmentum and the dentate nucleus.

Direct excitation of neck motoneurons by interstitiospinal fibers

1. Responses of neck motoneurons to stimulation of the interstitial nucleus of cajal (INC) were recorded intracellularly in cats under chloralose anesthesia. When stimuli were applied within or close to the INC, short latency, monosynaptic excitatory postsynaptic potentials (EPSPs) were evoked in many neck motoneurons. Such EPSPs were not evoked by stimulating mesencephalic regions outside the INC. 2. Stimulation of the ipsilateral INC produced monosynaptic EPSPs consistently in biventer cervicis-complexus (BCC) motoneurons, while such EPSPs were observed in about two thirds of the splenius (SP) motoneurons and half of the trapezius (TR) motoneurons tested. Stimulation of the contralateral INC produced weak monosynaptic EPSPs in about half the BCC motoneurons and in a few SP and TR motoneurons. All types of motoneurons also received longer latency, apparently polysynaptic, PSPs from both INCs. In BCC and TR motoneurons these were mainly EPSPs, in SP, mixed excitatory and inhibitory PSPs. 3. Monosynaptic EPSPs evoked by INC stimulation were not eliminated by acute and chronic parasagittal and transverse lesions placed to interrupt the bifurcating axons of all vestibulospinal and many reticulospinal neurons. No significant collision was observed between EPSPs evoked by INC and vestibular or reticular stimulation. The EPSPs evoked by stimulation of the INC therefore appear to have been produced by activation of interstitiospinal neurons rather than by an axon reflex mechanism. 4. The properties of a number of interstitiospinal neurons were observed while recording extracellularly from the mesencephalon to map the location of the INC. One third of the interstitiospinal neurons activated antidromically from the C4 segment could also be activated antidromically from L1. These lumbar-projecting neurons had conduction velocities ranging from 15--123 m/s. Several interstitiospinal neurons sending axons to the ventral horn of the neck segments were identified and two of these were found to be branching neurons that projected both to the neck and to lower levels of the spinal cord.