Nucleus Of Darkschewitsch Research Articles

Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons

Abstract The nucleus of Darkschewitsch (ND), mainly composed of GABAergic neurons, is widely recognized as a component of the eye-movement controlling system. However, the functional contribution of ND GABAergic neurons (NDGABA) in animal behavior is largely unknown. Here, we show that NDGABA neurons were selectively activated by different types of fear stimuli, such as predator odor and foot-shock. Optogenetic and chemogenetic manipulations revealed that NDGABA neurons mediate freezing behavior. Moreover, using circuit-based optogenetic and neuroanatomical tracing methods, we identified an excitatory pathway from the lateral periaqueductal grey (lPAG) to the ND that induces freezing by exciting ND inhibitory outputs to the motor-related gigantocellular reticular nucleus, ventral part (GiV). Together, these findings indicate the NDGABA population as a novel hub for controlling defensive response by relaying fearful information from lPAG to GiV, a mechanism critical for understanding how the freezing behavior is encoded in the mammalian brain.

Is there a primitive reflex residue underlying Marcus Gunn Syndrome? Rat electrophysiology.

To make an electrophysiological demonstration of a possible jaw muscle afferents-oculomotor neural pathway that was proposed by our previous works on rats, which substantiates an early "release hypothesis" on pathogenesis of human Marcus Gunn Syndrome (MGS). Extracellular unit discharge recording was applied and both orthodromic and spontaneous unitary firing were recorded in the oculomotor nucleus (III), and the complex of pre-oculomotor interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN), following electric stimulation of the ipsilateral masseter nerve (MN) in rats. Extracellular orthodromic unit discharges, with latencies of 3.7±1.3 and 4.7±2.9ms, were recorded unilaterally in the III, and the INC/DN neurons, respectively. Spontaneous unit discharges were also recorded mostly in the INC/DN and less frequently in the III. Train stimulation could prompt either facilitation or inhibition on those spontaneous unit discharges. The inhibition pattern of train stimulation on the spontaneous discharging was rather different in the III and INC/DN. A slow inhibitory pattern in which spontaneous firing rate decreased further and further following repeated train stimulation was observed in the III. While, some high spontaneous firing rate units, responding promptly to the train stimuli with a short-term inhibition and recovered quickly when stimuli are off, were recorded in the INC/DN. However, orthodromic unit discharge was not recorded in the III and INC/DN in a considerable number of experiment animals. A residual neuronal circuit might exist in mammals for the primitive jaw-eyelid reflex observed in amphibians, which might not be well-developed in all experimental mammals in current study. Nonetheless, this pathway can be still considered as a neuroanatomic substrate for development of MGS in some cases among all MGS with different kind of etiology.

Is Marcus Gunn jaw winking a primitive reflex? Rat neuroanatomy.

To investigate a possible trigeminal proprioceptive-oculomotor neural pathway and explore possible synaptic connections between neurons in this pathway. Attempt to bring a new insight to mechanism of Marcus Gunn syndrome (MGS). Anterograde and retrograde tract tracing was applied and combined with immunofluorescent stain in rats. After electrophysiological identifying mesencephalic trigeminal nucleus (Vme) neurons, intracellular injection of tracer was performed to trace axon trajectory. Following injections of anterograde tracers into the Vme, labeled terminals were observed ipsilateral in oculomotor and trochlear nuclei (III/IV), as well as in their premotor neurons in interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN). Combining with choline acetyltransferase (ChAT) immunofluorescent stain, it showed that Vme projecting terminals contact upon ChAT positive III/IV motoneurons under confocal microscope. By retrograde labeling premotor neurons of the III, it showed that Vme neuronal terminals contact with retrogradely labeled pre-oculomotor neurons in the INC/DN. Axons of intracellularly labeled Vme neurons that respond to electric stimuli of the masseter nerve traveled into the ipsilateral III. There may exist a trigeminal proprioceptive-oculomotor system neural circuit in the rat, which is probably related to vertical-torsional eye movements. Possible association of this pathway with MGS etiology was discussed.

Frontal eye field in prosimian galagos: Intracortical microstimulation and tracing studies.

The frontal eye field (FEF) in prosimian primates was identified as a small cortical region, above and anterior to the anterior frontal sulcus, from which saccadic eye movements were evoked with electrical stimulation. Tracer injections revealed FEF connections with cortical and subcortical structures participating in higher order visual processing. Ipsilateral cortical connections were the densest with adjoining parts of the dorsal premotor and prefrontal cortex (PFC). Label in a region corresponding to supplementary eye field (SEF) of other primates, suggests the existence of SEF in galagos. Other connections were with ventral premotor cortex (PMV), the caudal half of posterior parietal cortex, cingulate cortex, visual areas within the superior temporal sulcus, and inferotemporal cortex. Callosal connections were mostly with the region of the FEF of another hemisphere, SEF, PFC, and PMV. Most subcortical connections were ipsilateral, but some were bilateral. Dense bilateral connections were to caudate nuclei. Densest reciprocal ipsilateral connections were with the paralamellar portion of mediodorsal nucleus, intralaminar nuclei and magnocellular portion of ventral anterior nucleus. Other FEF connections were with the claustrum, reticular nucleus, zona incerta, lateral posterior and medial pulvinar nuclei, nucleus limitans, pretectal area, nucleus of Darkschewitsch, mesencephalic and pontine reticular formation and pontine nuclei. Surprisingly, the superior colliculus (SC) contained only sparse anterograde label. Although most FEF connections in galagos are similar to those in monkeys, the FEF-SC connections appear to be much less. This suggests that a major contribution of the FEF to visuomotor functions of SC emerged with the evolution of anthropoid primates.

Electromyography and Fos immunostaining study establish a possible functional link between trigeminal proprioception and the oculomotor system in rats.

The objective of this study was to explore whether there was a functional link between trigeminal proprioception and the oculomotor system mediated through jaw muscle afferents. Electromyography (EMG) was undertaken of the levator palpebrae (LP) and superior rectus (SR), and Fos expression was detected in the brainstem following consecutive down-stretching of the lower jaw at 2-4 Hz in rats. Retrograde tracing was undertaken of the interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN) pre-oculomotor neurons. EMG-like responses were recorded from the LP/SR during down-stretching of the lower jaw at 2-4 Hz in 3 out of 11 rats. Fos expression was induced by consecutive down-stretching of the lower jaw at 2-4 Hz for 20-30 seconds. Interestingly, Fos expression was distributed mainly in the bilateral INC/DN area. We also examined Fos-like immunoreactivity in central mesencephalic and paramedian pontine reticular formation that harbors premotor neurons controlling horizontal eye movement, but no Fos-like staining was observed therein. By injection of retrograde tracers into the oculomotor nucleus combined with Fos immunostaining, double labeled pre-oculomotor neurons were visualized to distribute in the INC/DN. In conclusions, there may exist a trigeminal proprioceptive – oculomotor system neural circuit through jaw muscle afferents in rats. Judging from Fos distribution pattern, this pathway might be related to vertical and torsional eye movements.

Gertrude Stein (1874–1946) and the nucleus of Darkschewitsch: a discursive commentary

Gertrude Stein is an icon of American literature whose scientific and medical background has become shrouded in obscurity. As an undergraduate at Radcliffe she was strongly influenced by William James and published two papers on motor automatism in the Psychological Review. As a medical student at Johns Hopkins University, her research on the nucleus of Darkschewitsch was quoted in Lewellys F Barker's acclaimed textbook on neuroanatomy; Stein's first book appearance. The background of the Russian neurologist Liverji O Darkschewitsch, little known in the West, is explored particularly in regard to his relationship and collaboration with Sigmund Freud whose letters provide considerable insight. Gertrude Stein failed to graduate with her class of 1901 at Johns Hopkins and soon after departed for an expatriate life in Europe devoted to art and literature.

Involvement of urocortinergic neurons below the midbrain central gray in the physiological response to restraint stress in pigeons

The present study was carried out to identify the diencephalic and midbrain neurons in pigeons that respond to stress (using restraint as the stressor) and determine if the urocortinergic neurons (expressing urocortin 1, Ucn1) below the midbrain central gray are among those activated. Immunolabeling for the immediate early gene Egr-1 was used to identity stress-responsive neurons, following 1–3 h of restraint. A large increase in nuclear Egr-1 immunolabeling was observed in several dorsomedial thalamic nuclei, and in a stream of neurons extending from below the mesencephalic central gray (overlapping the nucleus of Darkschewitsch at these levels) to just anterior to the nucleus of Edinger–Westphal. A more modest increase in neuronal nuclear Egr-1 was observed in the medial posterior hypothalamic area, the mesencephalic periventricular area, the ventral tegmental area, the inferior colliculus, the nucleus paramedianus of the midbrain, and the intercollicular nucleus. The distribution and abundance of urocortin-immunolabeled neurons coincided with that of the stress-responsive neurons below the mesencephalic periaqueductal gray, and about 50% of these urocortin neurons were activated by stress. These results suggest that, as in some mammals, the urocortinergic neurons of the paramedian subgriseal mesencephalon respond to stress. In those mammals, in which the boundaries of the nucleus of Edinger–Westphal are indistinct, the caudal part of the homologous field of urocortinergic neurons has been referred to as the nucleus of Edinger–Westphal. In pigeons, in which the nucleus of Edinger–Westphal is cytoarchitectonically well-defined, the caudal part of this urocortinergic field clearly does not include the nucleus of Edinger–Westphal.

Parinaud′s syndrome in a patient with thalamic infarction due to cerebral venous thrombosis

Dear Editor, The dorsal midbrain syndrome, characterized by upward gaze paralysis, convergence-retraction nystagmus and light-near dissociation owes its eponym to the French ophthalmologist, Henri Parinaud. Pineal tumors, intrinsic midbrain lesions and hydrocephalus or aqueductal enlargement compressing the posterior commissure are frequently implicated causes. We report a patient with thrombosis of the deep cerebral venous system (CVT) who presented with Parinaud's syndrome. Isolated eye signs are seldom discussed in CVT and Parinaud's syndrome has not been described. A diagnosis of "benign" intracranial hypertension (BIH) was proffered in a 30-year-old man with blurred vision, papilledema and normal brain magnetic resonance imaging (MRI). Lumbar puncture tapped clear cerebrospinal fluid (CSF) under opening pressure of 350 mmH2O; CSF analysis was normal. Obtaining no relief, he was referred for re-evaluation. Visual acuity was 20/20 and perimetry mapped full visual fields without blind spot enlargement. Bilateral papilledema and convergence-retraction nystagmus was noted; equal pupils constricted well during accommodation but sluggishly to light. Upgaze was absent, eyelids retracted on looking up (Collier's sign), downward saccades and pursuit were normal. Neurological examination was otherwise unremarkable. The lesion was clinically localized to the dorsal mesencephalon and MRI was repeated [Fig. 1]. Cerebral venogram revealed unilateral posterior thalamic infarction with thrombosis involving multiple cerebral venous sinuses [Fig. 2]. The third ventricle and aqueduct were not enlarged.Figure 1: T2 weighted axial MR image depicting altered hyperintense signal involving the right thalamus. The signal was hypointense on T1 and suggests infarction. To the right, a T2 weighted sagittal MR image shows a hyperintense signal replacing the normal flow void in the great cerebral vein of Galen (arrowhead), straight sinus, torcula (short arrow) and superior sagittal sinus (long arrow)Figure 2: MR venogram sagittal view shows absent flow in superior sagittal, straight, lateral and sigmoid sinuses and poor filling of the deep venous systemPremotor structures mediating vertical gaze lie in the periaqueductal paramedian nuclei of the midbrain reticular formation. The nuclei responsible are the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), posterior commissure and its nucleus, nucleus of Darkschewitsch and interstitial nucleus of Cajal (INC). Medium-lead burst neurons in riMLF generate vertical saccades1 while INC controls vertical slow movements and gaze integration. The posterior commissure is particularly important in mediating upward gaze. Although typically caused by bilateral involvement, upgaze paresis may result from unilateral midbrain lesions that disrupt posterior commissural connections.2 Intracranial hypertension could arguably cause upgaze palsy and papilledema even before ventricular dilatation is apparent.3 However, gaze palsy developed despite cerebral decongestant measures and persisted after CSF pressure had normalized. Our subject had venous thalamic infarction without obvious midbrain involvement but vertical gaze disturbances could result from concomitant undetected microinfarcts in dorsal mesencephalic structures that share a common vascular supply.45 Arterial thalamic infarcts may be associated with upgaze paresis, probably because of interruption of supranuclear pathways mediating vertical gaze.5 Patients with venous thalamic infarction are often obtunded and isolated eye signs are rarely reported. Thrombosis involving dural venous sinuses and deep cerebral veins may masquerade as BIH. MRI with venography is the technique of choice to diagnose CVT but may miss partial or early disease as described here. Thrombosis appears as absent flow void on spin-echo images and lack of signal in angiographic images. Decreased signal on T2 weighted imaging in early CVT may be confused with normal flow void and imaging at intermediate field strengths becomes necessary. We emphasize caution in diagnosing BIH when ocular motility disturbances are present and advocate repeated scanning directed by a high index of clinical suspicion.

Immunocytochemical visualization of d-glutamate in the rat brain

Using highly specific antisera directed against conjugated d-amino acids, the distribution of d-glutamate-, d-tryptophan-, d-cysteine-, d-tyrosine- and d-methionine-immunoreactive structures in the rat brain was studied. Cell bodies containing d-glutamate, but not d-glutamate-immunoreactive fibers, were found. Perikarya containing this d-amino acid were only found in the mesencephalon and thalamus of the rat CNS. Thus, the highest density of cell bodies containing d-glutamate was observed in the dorsal raphe nucleus, the ventral part of the mesencephalic central gray, the superior colliculus, above the posterior commissure, and in the subparafascicular thalamic nucleus. A moderate density of immunoreactive cell bodies was observed in the dorsal part of the mesencephalic central gray, above the rostral linear nucleus of the raphe, the nucleus of Darkschewitsch, and in the medial habenular nucleus, whereas a low density was found below the medial forebrain bundle and in the posterior thalamic nuclear group. Moreover, no immunoreactive fibers or cell bodies were visualized containing d-tryptophan, d-cysteine, d-tyrosine or d-methionine in the rat brain. The distribution of d-glutamate-immunoreactive cell bodies in the rat brain suggests that this d-amino acid could be involved in several physiological mechanisms. This work reports the first visualization and the morphological characteristics of conjugated d-glutamate-immunoreactive cell bodies in the rat CNS using an indirect immunoperoxidase technique. Our results suggest that the immunoreactive neurons observed have an uptake mechanism for d-glutamate.

Polysynaptic inputs to vestibular efferent neurons as revealed by viral transneuronal tracing

The Bartha strain of the alpha-herpes pseudorabies virus (PrV) was used as a retrograde transneuronal tracer to map synaptic inputs to the vestibular efferent neurons of the Mongolian gerbil, Meriones unguiculatus. Although previous experiments have shown that vestibular efferent neurons respond to visual motion and somatosensory stimuli, the anatomic connections mediating those responses are unknown. PrV was injected unilaterally into the horizontal semicircular canal neuroepithelium of gerbils, where it was taken up by efferent axon terminals. The virus was then retrogradely transported to efferent cell bodies, replicated, and transported into synaptic endings projecting onto the efferent cells. Thirty animals were sacrificed at approximately 5-h increments between 75 and 105 h post-infection after determining that shorter time points had no central infection. Infected cells were visualized immunohistochemically. Temporal progression of neuronal infection was used to determine the nature of primary and higher order projections to the vestibular efferent neurons. Animals sacrificed at 80-94 h post-inoculation exhibited immunostaining in the dorsal and ventral group of vestibular efferent neurons, predominately on the contralateral side. Neurons within the medial, gigantocellular, and lateral reticular formations were among the first cells infected thereafter. At 95 h, additional virus-labeled cell groups included the solitary, area postrema, pontine reticular, prepositus, dorsal raphe, tegmental, the subcoeruleus nuclei, the nucleus of Darkschewitsch, and the inferior olivary beta and ventrolateral subnuclei. Analysis beyond 95 h revealed virus-infected neurons located in the vestibulo-cerebellar and motor cortices. Paraventricular, lateral, and posterior hypothalamic cells, as well as central amygdala cells, were also labeled. Spinal cord tissue exhibited no labeling in the intermediolateral cell column, but scattered cells were found in the central cervical nucleus. The results suggest functional associations among efferent feedback regulation of labyrinthine sensory input and both behavioral and autonomic systems, and support a closed-looped vestibular feedback model with additional open-loop polysynaptic inputs.

Olivary projection from the rostral part of the nucleus of Darkschewitsch in the postnatal rat as revealed through the use of a carbocyanine dye

Using a carbocyanine dye in postnatal rats, we have shown that the rostral part of the nucleus of Darkschewitsch (ND), consisting of a subnucleus of the so-called “area parafascicularlis prerubralis ” and excluded from the rat's ND proper, projects ipsilaterally to the rostral part of the medial accessory olive. The present study suggests the existence of a precise topographic organization from subnuclei of the area parafascicularlis prerublaris to subnuclei of the inferior olive.

Sergej Sergejewitsch Korsakow (1854–1900)

Back to table of contents Previous article Next article Images in PsychiatryFull AccessSergej Sergejewitsch Korsakow (1854–1900)Stephanie Krüger, M.D., and Peter Bräunig, M.D.Stephanie KrügerSearch for more papers by this author, M.D., and Peter BräunigSearch for more papers by this author, M.D.Published Online:1 Jun 2004https://doi.org/10.1176/appi.ajp.161.6.974AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Sergej Sergejewitsch Korsakow was born in 1854 in the little village of Gus-Chrustalny, 250 km south of Moscow. His father was an administrator in a big crystal factory, for which the village was known (“chrustal” means crystal). At the age of 16, he finished high school, having earned the “golden medal” for academic excellency. After studying medicine at Moscow University (1870–1875), Korsakow worked for a year at the Preoprashenki psychiatric hospital. He continued his residency training at a famous neurological institute run by the epileptologist Kojewnikow. His fellow residents included Darkschewitsch (of the Darkschewitsch nucleus), Roth (of Roth’s disease and meralgia paresthetica), Rossolimo (of the Rossolimo reflex), and Minor (of the epiconus minori and the Minor sweat test).Afterward, he returned to the Preoprashenki psychiatric hospital, where he worked until 1879. His interests lay more in neurology than in psychiatry though, and he was convinced that all psychiatric disorders could be deduced to dysfunctions in brain activity. He refused to accept psychopathological interpretations of mental dysfunction: “Basic scientists must regard psychiatric disturbances as very complex reflexes” (1). Based on this conviction, he started investigating neurological disturbances related to alcohol abuse. In 1887, he published his famous article titled “Polyneuritic Psychosis With Disturbance of Memory and Pseudoreminiscences,” which earned him worldwide fame, and the condition was renamed “Korsakow’s Disease” shortly after its first publication (2).Nevertheless, Korsakow’s academic life in Russia was difficult. In 1898, he finally became professor and head of psychiatry at the University of Moscow. By that time, he had traveled extensively in Europe and had met Emil Kraepelin, Paul Flechsig, Richard von Krafft-Ebbing, and Arnold Pick.During his time, Korsakow was the most popular psychiatrist in Moscow. Patients liked him for his empathic manner, and his residents admired his diagnostic skills. Despite or maybe because of his biological approach to psychiatric disorders, he was one of the protagonists of the “no-restraint” method in psychiatric hospitals and urged his residents to “treat the patients as human beings” and to be “interested in their biography” (3). He also introduced physical examinations to the psychiatric diagnostic routine to link psychiatry to physiology and neurology. For more than 20 years, Korsakow’s 1893 textbook on psychiatric disorders was the gold standard for medical students and residents (1).Korsakow died of heart disease at age 46. In the same year, he had founded the Journal of Neurology and Psychiatry S.S. Korsakow, which is still the leading psychiatric journal in Russia.Address reprint requests to Dr. Bräunig, Klinik für Psychiatrie, Verhaltensmedizin und Psychosomatik am Klinikum Chemnitz, Dresdner Str. 178, 09131 Chemnitz, Germany; [email protected] (e-mail). Photograph courtesy of Dr. Bräunig. Sergej Sergejewitsch Korsakow

Intergeniculate leaflet and ventral lateral geniculate nucleus afferent connections: An anatomical substrate for functional input from the vestibulo‐visuomotor system

The intergeniculate leaflet (IGL) has widespread projections to the basal forebrain and visual midbrain, including the suprachiasmatic nucleus (SCN). Here we describe IGL-afferent connections with cells in the ventral midbrain and hindbrain. Cholera toxin B subunit (CTB) injected into the IGL retrogradely labels neurons in a set of brain nuclei most of which are known to influence visuomotor function. These include the retinorecipient medial, lateral and dorsal terminal nuclei, the nucleus of Darkschewitsch, the oculomotor central gray, the cuneiform, and the lateral dorsal, pedunculopontine, and subpeduncular pontine tegmental nuclei. Intraocular CTB labeled a retinal terminal field in the medial terminal nucleus that extends dorsally into the pararubral nucleus, a location also containing cells projecting to the IGL. Distinct clusters of IGL-afferent neurons are also located in the medial vestibular nucleus. Vestibular projections to the IGL were confirmed by using anterograde tracer injection into the medial vestibular nucleus. Other IGL-afferent neurons are evident in Barrington's nucleus, the dorsal raphe, locus coeruleus, and retrorubral nucleus. Injection of a retrograde, trans-synaptic, viral tracer into the SCN demonstrated transport to cells as far caudal as the vestibular system and, when combined with IGL injection of CTB, confirmed that some in the medial vestibular nucleus polysynaptically project to the SCN and monosynaptically to the IGL, as do cells in other brain regions. The results suggest that the IGL may be part of the circuitry governing visuomotor activity and further indicate that circadian rhythmicity might be influenced by head motion or visual stimuli that affect the vestibular system.

The premotor region essential for rapid vertical eye movements shows early involvement in Alzheimer's disease-related cytoskeletal pathology

The rostral interstitial nucleus of the medial longitudinal fascicle (riMLF) contains premotor neurons essential for the generation of rapid vertical eye movements. The Alzheimer's disease (AD)-related cytoskeletal changes and β-amyloid deposits in this nucleus were examined in 30 autopsy cases and compared to the involvement of three associated nuclei — Edinger–Westphal nucleus, nucleus of Darkschewitsch and interstitial nucleus of Cajal. The riMLF displays slight cytoskeletal alterations already in the early stages in the development of the cortical cytoskeletal pathology (cortical NFT/NT-stages I–II, representing the preclinical phase of AD). In the cortical NFT/NT-stages III–IV (i.e. incipient phase of AD), the cytoskeletal pathology in the riMLF is pronounced and in stages V–VI (i.e. clinical phase of AD) it is severe. The progression of the cytoskeletal pathology in the riMLF correlates significantly with the cortical NFT/NT-stages I–VI that reflect the clinical course of AD. Isolated β-amyloid deposits appear in the riMLF for the first time in the final β-amyloid stage. In the Edinger–Westphal nucleus, in the nucleus of Darkschewitsch and most markedly in the interstitial nucleus of Cajal, the pathological changes were significantly less severe than those in the riMLF. In the event that the cytoskeletal pathology impairs the function of the premotor neurons of the riMLF, one would predict a progressive slowing of vertical saccades corresponding to the advancing cortical NFT/NT-stages.

Connections of the medial posterior parietal cortex (area 7m) in the monkey

The afferent and efferent cortical and subcortical connections of the medial posterior parietal cortex (area 7m) were studied in cebus (Cebus apella) and macaque (Macaca fascicularis) monkeys using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique. The principal intraparietal corticocortical connections of area 7m in both cebus and macaque cases were with the ipsilateral medial bank of the intraparietal sulcus (MIP) and adjacent superior parietal lobule (area 5), inferior parietal lobule (area 7a), lateral bank of the IPS (area 7ip), caudal parietal operculum (PGop), dorsal bank of the caudal superior temporal sulcus (visual area MST), and medial prestriate cortex (including visual area PO and caudal medial lobule). Its principal frontal corticocortical connections were with the prefrontal cortex in the shoulder above the principal sulcus and the cortex in the shoulder above the superior ramus of the arcuate sulcus (SAS), the area purported to contain the smooth eye movement-related frontal eye field (FEFsem) in the cebus monkey by other investigators. There were moderate connections with the cortex in the rostral bank of the arcuate sulcus (purported to contain the saccade-related frontal eye field; FEFsac), supplementary eye field (SEF), and rostral dorsal premotor area (PMDr). Area 7m also had major connections with the cingulate cortex (area 23), particularly the ventral bank of the cingulate sulcus. The principal subcortical connections of area 7m were with the dorsal portion of the ventrolateral thalamic (VLc) nucleus, lateral posterior thalamic nucleus, lateral pulvinar, caudal mediodorsal thalamic nucleus and medial pulvinar, central lateral, central superior lateral, and central inferior intralaminar thalamic nuclei, dorsolateral caudate nucleus and putamen, middle region of the claustrum, nucleus of the diagonal band, zona incerta, pregeniculate nucleus, anterior and posterior pretectal nuclei, intermediate layer of the superior colliculus, nucleus of Darkschewitsch and dorsomedial parvicellular red nucleus (macaque cases only), dorsal, dorsolateral and lateral basilar pontine nuclei, nucleus reticularis tegmenti pontis, locus ceruleus, and superior central nucleus. The findings are discussed in terms of the possibility that area 7m contains a "medial parietal eye field" and belongs to a neural network of oculomotor-related structures that plays a role in the control of eye movement.

The efferent connections to the thalamus and brainstem of the physiologically defined eye field in the rat medial frontal cortex

The anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into sites of the rat frontal eye field (FEF) located in the medial frontal cortex. After a single iontophoretic injection of PHA-L into a FEF site where intracortical microstimulation elicited eye movements, anterogradely labelled fibres and terminal-like elements were found in the thalamus in the anterior nuclei, intralaminar nuclei, lateral portion of the mediodorsal nucleus and posterior nuclear group. In the midbrain and pons, labelled fibres were located in the anterior pretectal area, Darkschewitsch nucleus, superior colliculus and dorsolateral portion of the central gray. When the tracer was injected at the FEF periphery, at a site the stimulation of which evoked both eye and whisker movements, labelling distribution in the thalamus differed from that observed after FEF injections, while a similar distribution was observed in the brainstem. In the thalamus, anterograde labelling was observed in these latter cases in the anterior nuclei, ventral nuclei, medial portion of the laterodorsal nucleus. The present findings point out that the FEF and FEF periphery are connected with numerous subcortical structures of the thalamus and brainstem. In addition, the connections of FEF and FEF periphery with the thalamus differ, whereas the midbrain and pons connections of the two subdivisions share common targets.

Periaqueductal gray matter projections to midline and intralaminar thalamic nuclei of the rat.

The periaqueductal gray matter (PAG) projections to the intralaminar and midline thalamic nuclei were examined in rats. Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected in discrete regions of the PAG, and axonal labeling was examined in the thalamus. PHA-L was also placed into the dorsal raphe nuclei or nucleus of Darkschewitsch and interstitial nucleus of Cajal as controls. In a separate group of rats, the retrograde tracer cholera toxin beta-subunit (CTb) was injected into one of the intralaminar thalamic nuclei-lateral parafascicular, medial parafascicular, central lateral (CL), paracentral (PC), or central medial nucleus-or one of the midline thalamic nuclei-paraventricular (PVT), intermediodorsal (IMD), mediodorsal, paratenial, rhomboid (Rh), reuniens (Re), or caudal ventral medial (VMc) nucleus. The distribution of CTb labeled neurons in the PAG was then mapped. All PAG regions (the four columns of the caudal two-thirds of the PAG plus rostral PAG) and the precommissural nucleus projected to the rostral PVT, IMD, and CL. The ventrolateral, lateral, and rostral PAG provided additional inputs to most of the other intralaminar and midline thalamic nuclei. PAG inputs to the VMc originated from the rostral and ventrolateral PAG areas. In addition, the lateral and rostral PAG projected to the zona incerta. No evidence was found for a PAG input to the ventroposterior lateral parvicellular, ventroposterior medial parvicellular, caudal PC, oval paracentral, and reticular thalamic nuclei. PAG --> thalamic circuits may modulate autonomic-, nociceptive-, and behavior-related forebrain circuits associated with defense and emotional responses.

Review : Evolution of the Motor System: Why the Elephant's Trunk Works Like a Human's Hand

The nucleus of Darkschewitsch, the nucleus accessorius medialis of Bechterew, and the parvicellular red nucleus in the mammalian mesodiencephalon fuse with each other and thus have borders that are not always distinct. These structures project topographically to the inferior olive and receive inputs from motor cortex, premotor cortex, substantia nigra, and cerebellar nuclei, which suggests that these nuclei play an important role in mammalian motor control. Furthermore, the nuclei show developmental differences that correspond with species-specialized body parts, such as the human's hand, the axial muscular system of the whale, and the elephant's trunk, to name just a few. We focus here on the differences in these meso diencephalo-olivo-cerebellar projections among certain mammals and propose that these brain structures are altered as the animal's gross anatomy alters. We also suggest that well-developed mesodiencephalo olivo-cerebellar projections may be an important factor for the differentiation of the large neocortex of the human, primate, elephant, and whale during evolutionary progress. NEUROSCIENTIST 5:217-226, 1999

Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat

Orphanin FQ (OFQ) is the endogenous agonist of the opioid receptor-like receptor (ORL-1). It and its precursor, prepro-OFQ, exhibit structural features suggestive of the opioid peptides. A cDNA encoding the OFQ precursor sequence in the rat recently has been cloned, and the authors recently generated a polyclonal antibody directed against the OFQ peptide. In the present study, the authors used in situ hybridization and immunohistochemistry to examine the distribution of OFQ peptide and mRNA in the central nervous system of the adult rat. OFQ immunoreactivity and prepro-OFQ mRNA expression correlated virtually in all brain areas studied. In the forebrain, OFQ peptide and mRNA were prominent in the neocortex endopiriform nucleus, claustrum, lateral septum, ventral forebrain, hypothalamus, mammillary bodies, central and medial nuclei of the amygdala, hippocampal formation, paratenial and reticular nuclei of the thalamus, medial habenula, and zona incerta. No OFQ was observed in the pineal or pituitary glands. In the brainstem, OFQ was prominent in the ventral tegmental area, substantia nigra, nucleus of the posterior commissure, central gray, nucleus of Darkschewitsch, peripeduncular nucleus, interpeduncular nucleus, tegmental nuclei, locus coeruleus, raphe complex, lateral parabrachial nucleus, inferior olivary complex, vestibular nuclear complex, prepositus hypoglossus, solitary nucleus, nucleus ambiguous, caudal spinal trigeminal nucleus, and reticular formation. In the spinal cord, OFQ was observed throughout the dorsal and ventral horns. The wide distribution of this peptide provides support for its role in a multitude of functions, including not only nociception but also motor and balance control, special sensory processing, and various autonomic and physiologic processes. J. Comp. Neurol. 406:503–547, 1999. © 1999 Wiley-Liss, Inc.

Localization of orphanin FQ (nociceptin) peptide and messenger RNA in the central nervous system of the rat

Orphanin FQ (OFQ) is the endogenous agonist of the opioid receptor-like receptor (ORL-1). It and its precursor, prepro-OFQ, exhibit structural features suggestive of the opioid peptides. A cDNA encoding the OFQ precursor sequence in the rat recently has been cloned, and the authors recently generated a polyclonal antibody directed against the OFQ peptide. In the present study, the authors used in situ hybridization and immunohistochemistry to examine the distribution of OFQ peptide and mRNA in the central nervous system of the adult rat. OFQ immunoreactivity and prepro-OFQ mRNA expression correlated virtually in all brain areas studied. In the forebrain, OFQ peptide and mRNA were prominent in the neocortex endopiriform nucleus, claustrum, lateral septum, ventral forebrain, hypothalamus, mammillary bodies, central and medial nuclei of the amygdala, hippocampal formation, paratenial and reticular nuclei of the thalamus, medial habenula, and zona incerta. No OFQ was observed in the pineal or pituitary glands. In the brainstem, OFQ was prominent in the ventral tegmental area, substantia nigra, nucleus of the posterior commissure, central gray, nucleus of Darkschewitsch, peripeduncular nucleus, interpeduncular nucleus, tegmental nuclei, locus coeruleus, raphe complex, lateral parabrachial nucleus, inferior olivary complex, vestibular nuclear complex, prepositus hypoglossus, solitary nucleus, nucleus ambiguous, caudal spinal trigeminal nucleus, and reticular formation. In the spinal cord, OFQ was observed throughout the dorsal and ventral horns. The wide distribution of this peptide provides support for its role in a multitude of functions, including not only nociception but also motor and balance control, special sensory processing, and various autonomic and physiologic processes.