Evidence that non-NMDA receptors are involved in the excitatory pathway from the pedunculopontine region to nigrostriatal dopaminergic neurons

Summary Extracellular single-neuron recordings were obtained from electrophysiologically identified nigrostriatal neurons in chloral hydrate anesthetized rats, in order to test the hypothesis that excitatory amino acid receptors are involved in responses of these neurons to electrical stimulation of the pontine region where the pedunculopontine nucleus (PPN) is located. The effects of iontophoretic application of excitatory amino acids and their antagonists as well as of cholinergic antagonists were tested on the fast orthodromic excitation of nigrostriatal neurons evoked by stimulation of the PPN region. The N-methyl-D-aspartate (NMDA) receptor antagonist D-a-aminoadipic acid as well as the cholinergic receptor antagonists mecamylamine and atropine failed to suppress the synaptic excitation of nigral neurons. The NMDA receptor antagonist DL-2-amino-5-phosphonovalerate exerted a weak depressant action on the synaptic response in a few neurons only. On the contrary, the broad spectrum antagonists of excitatory amino acid receptors kynurenic acid and gamma-Dglutamyl-amino-methyl-sulphonate were found to block simultaneously both the synaptic excitation and the neuronal responses to iontophoretic pulses of glutamate while leaving unaffected the neuronal responses to local application of acetylcholine or carbachol. The competitive antagonist of non-NMDA receptors 6-cyano-2,3-dihy-droxy-7-nitro-quinoxaline suppressed the synaptic excitation at ejection currents which antagonized neuronal responses to quisqualate and kainate. These results suggest that PPN excitatory fibers synapsing onto pars compacta nigrostriatal neurons utilize an excitatory amino acid as a synaptic transmitter acting preferentially on non-NMDA receptors.     

A role for the basal ganglia in nicotinic modulation of the blink reflex

Summary In humans and rats we found that nicotine transiently modifies the blink reflex. For blinks elicited by stimulation of the supraorbital branch of the trigeminal nerve, nicotine decreased the magnitude of the orbicularis oculi electromyogram (OOemg) and increased the latency of only the long-latency (R2) component. For blinks elicited by electrical stimulation of the cornea, nicotine decreased the magnitude and increased the latency of the single component of OOemg response. Since nicotine modified only one component of the supraorbitally elicited blink reflex, nicotine must act primarily on the central nervous system rather than at the muscle. The effects of nicotine could be caused by direct action on lower brainstem interneurons or indirectly by modulating descending systems impinging on blink interneurons. Since precollicular decerebration eliminated nicotine's effects on the blink reflex, nicotine must act through descending systems. Three lines of evidence suggest that nicotine affects the blink reflex through the basal ganglia by causing dopamine release in the striatum. First, stimulation of the substantia nigra mimicked the effects of nicotine on the blink reflex. Second, haloperidol, a dopamine (D₂) receptor antagonist, blocked the effect of nicotine on the blink reflex. Third, apomorphine, a D₂ receptor agonist, mimicked the effects of nicotine on the blink reflex.     

Ascending and descending components of the medial forebrain bundle in the rat as demonstrated by the horseradish peroxidase-blue reaction

Summary The ascending and descending components of the medial forebrain bundle (MFB) were investigated by means of horseradish peroxidase (HRP) with a sensitive substrate. The HRP was injected iontophoretically into the MFB at various levels from the anterior commissure to the posterior hypothalamus. In order to prevent the diffusion of HRP to other brain areas, a double micropipette system was used. The descending components of the MFB are derived from (1) the anterior cingulate area, infra- or prelimbic area, and sulcal cortex, (2) the lateral septal nucleus and diagonal band, (3) the bed nucleus of the stria terminalis, (4) the paraventricular nucleus (5) the substantia innominata, (6) the amygdaloid complex (AM), (7) the ventromedial (VM) and dorsomedial (DM) hypothalamic nuclei, (8) the entopeduncular nucleus and (9) nucleus periventricularis stellatocellularis. The ascending components of the MFB originate in: (1) the medial preoptic nucleus, (2) the nucleus periventricularis stellatocellularis and rotundocellularis, (3) the posterior hypothalamic nucleus, (4) the parafascicular nucleus, (5) the ventral premammillary nucleus, (6) the substantia grisea periventricularis, (7) the lateral habenular nucleus, (8) the VM and DM, (9) the paratenial nucleus, (10) the AM and (11) the arcuate nucleus.Abbreviations used in Figures and Tables a nucleus accumbens - abl nucleus amygdaloideus basalis, pars lateralis - abm nucleus amygdaloideus basalis, pars medialis - ac nucleus amygdaloideus centralis - AC anterior cingulate area - al nucleus amygdaloideus lateralis - am nucleus amygdaloideus medialis - ar nucleus arcuatus - CC tractus corporis callosi - CSDV commissura supraoptica dorsalis, pars ventralis - DB diagonal band - DM nucleus dorsomedialis hypothalami - EP nucleus entopeduncularis - ha nucleus anterior hypothalami - hl nucleus lateralis hypothalami - hp nucleus posterior hypothalami - IL infralimbic area of frontal cortex - lh nucleus habenulae lateralis - LH₁ medial forebrain bundle (MFB) at the level of commissura anterior - LH₂ lateral preoptic area - LH₃ MFB at the level of the nucleus anterior hypothalami - LH₄ MFB at the level of the nucleus ventromedialis hypothalami - LH₅ MFB at the level of the nucleus posterior hypothalami - MFB medial forebrain bundle - pf nucleus parafascicularis - PL prelimbic area of frontal cortex - pol nucleus preopticus lateralis - pom nucleus preopticus medialis - posc nucleus preopticus, pars suprachiasmatica - pt nucleus parataenialis - pv nucleus premamillaris ventralis - PV nucleus paraventricularis - pvs nucleus periventricularis stellatocellularis - pvr nucleus periventricularis rotundocellularis - SC sulcal cortex - SGPV substantia grisea periventricularis - SI substantia innominata - SL lateral septal nucleus - ST bed nucleus of stria terminalis - sum nucleus supramamillaris - TO tractus opticus - tmm nucleus medialis thalami, pars medialis - VM nucleus ventromedialis hypothalami The nomenclature used in this paper is according to König and Klippel's Stereotaxic Atlas (1967).     

A lectin horseradish peroxidase study of the origin of ascending fibers in the medial forebrain bundle of the rat. The upper brainstem

The origins of projections within the medial forebrain bundle from the upper brainstem were examined with the horseradish peroxidase technique. Labeled cells were found in approximately 15 upper brainstem nuclei following injections of a conjugate of horseradish peroxidase and wheat germ agglutinin at various levels of the medial forebrain bundle. Labeled nuclei included (from caudal to rostral): dorsal and ventral parabrachial nuclei; Kolliker-Fuse nucleus; dorsolateral tegmental nucleus; A7 (lateral pontine tegmentum medial to lateral lemniscus); median and dorsal raphe nuclei; distinct group of cells oriented mediolaterally in the dorsal pontine tegmentum below the central gray; B9 (ventral midbrain tegmentum dorsal to medial lemniscus); retrorubral nucleus; nucleus of Darkschewitsch, interfascicular nucleus; rostral and caudal linear nuclei; ventral tegmental area; medial part of substantia nigra, pars compacta; and the supramammillary nucleus. With the exception of the ventral parabrachial nucleus, Kolliker-Fuse, A7, B9 and substantia nigra, pars compacta, each of the nuclei mentioned above sent strong projections along the medial forebrain bundle to the rostral forebrain. Sparse labeling was observed throughout the pontine and midbrain reticular formation. With the exception of the dorsal raphe nucleus, projections to the most anterior regions of the medial forebrain bundle (level of the anterior commissure) essentially only arose from presumed dopamine-containing nuclei-retrorubral nucleus (A8 area), interfascicular nucleus, rostral and caudal linear nuclei, substantia nigra pars compacta, and ventral tegmental area. Evidence was reviewed indicating that major forebrain sites of termination for these dopaminergic nuclei are structures that have been collectively referred to as the 'ventral striatum'. It is concluded from the present findings that several pontine and mesencephalic cell groups are in a position to exert a strong, direct effect on structures in the anterior forebrain and that the medial forebrain bundle is the main communication route between the upper brainstem and the forebrain.     

成年大鼠基底前脑隔-斜角带复合体的巢蛋白免疫阳性神经元至海马的纤维投射

目的 观察大鼠基底前脑巢蛋白(nestin)免疫阳性神经元的纤维投射。方法 先用荧光素逆行追踪法显示基底前脑内投射至海马的荧光素标记神经元，观察摄片后再进行nestin免疫组织化学染色。对比荧光照片和免疫组织化学染色照片，辨认荧光素和nestin双标神经元。结果 在基底前脑注射侧的内侧隔核(MS)和斜角带核的垂直支(vDB)和水平支(hDB)均存在荧光素标记细胞，其中一部分为nestin免疫阳性。在MS、vDB和hDB，双标细胞占逆行标记细胞的比例分别为21．3％、25％和20．6％；占nestin阳性细胞的比例分别为26．6％、15．7％和16．3％。结论 大鼠基底前脑的nestin免疫阳性神经元发出神经纤维向海马投射。提示在基底前脑有一个平行于隔-海马胆碱能投射和GABA能投射的第3条通路。     

Peripheral nerve grafts lacking viable Schwann cells fail to support central nervous system axonal regeneration

Summary Peripheral nerve grafts were implanted bilaterally into the diencephalon of adult hamsters. One graft segment contained both viable Schwann cells and their basal lamina tubes. The Schwann cell population in the second graft segment was killed by freezing prior to implantation. Seven weeks after graft implantations, the extracranial end of each graft segment was exposed, transected and labelled with a fluorescent tracer substance. One week after the labelling procedure each animal was perfused and the diencephalon and midbrain were examined. Ultrastructural analyses of both types of graft demonstrated the persistence of the Schwann cell-derived basal lamina tubes. Retrogradely labelled neurons were found in all cases in which an intact graft remained in place for two months, but were seen in only one case with a frozen graft. Large numbers of myelinated and unmyelinated axons were seen within the intact grafts, but no axons were found in the previously frozen grafts. These results indicate that lesioned CNS axons are able to regenerate vigorously when provided with an environment which includes viable Schwann cells. But, CNS axons regenerate less well, if at all, when Schwann cells are absent. Further, it appears that Schwann cell-derived basal lamina tubes, when isolated from their parent cells, are insufficient to initiate or sustain CNS axonal regeneration.This material is based upon work supported by the National Science Foundation under grant BNS-8416911     

鸡胚发育过程中端脑神经元凋亡的分布

目的：研究鸡胚发育过程中端脑神经细胞凋亡的时空分布。方法：采用硫堇染色、TUNEL法染色观察凋亡神经细胞的分布。透射电镜技术观察细胞的超微结构的变化。结果：鸡胚第5d、第6d时可见少量凋亡细胞，随着鸡胚的发育，凋亡细胞渐渐增多。鸡胚第7d时，凋亡细胞数达到高峰，随后数量渐渐减少。鸡胚第12d时，几乎不见凋亡细胞。凋亡细胞主要分布于嘴段背侧和两侧脑室之间的组织等部位。透射电镜观察到凋亡细胞的超微结构的改变。结论：鸡胚神经系统发育中选择性发生神经元凋亡，凋亡细胞的分布呈现一定的时空规律。     

Effect of injury to the zone of the medial forebrain bundle and preoptic region on activity of an epileptiform focus induced by penicillin (on the phenomenon of the hyperactive determinant dispatch station)

Experiments on cats showed that injury to the medial forebrain bundle (MFB) and also partly to the preoptic region on the side of application of penicillin to the cerebral cortex (middle suprasylvian gyrus) causes depression of paroxysmal activity (spike potentials) in the penicillin focus, and also in a secondary mirror focus arising in the symmetrical zone of the opposite cortex. Injury to MFB on the side of the mirror focus causes depression of paroxysmal spike potentials only in that focus and does not affect activity in the primary epileptiform focus. The effects described are examined from the standpoint of views regarding the role of the determinant dispatch station (DDS) in the activity of the CNS: A primary epileptiform focus is a hyperactive DDS which induces the appearance of secondary foci, supports them, and determines the character of their activity. The results of the investigation suggests a role for MFB in the modulation of cortical epileptiform activity.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathophysiology, Academy of Medical Sciences of the USSR, Moscow. Laboratory of Electrophysiology, V. F. Filatov Odessa Research Institute for Eye Diseases and Tissue Therapy, Ministry of Health of the Ukrainian SSR. Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 82, No. 12, pp. 1413–1416, December, 1976.     

Role of primate basal ganglia and frontal cortex in the internal generation of movements

In order to more comprehensively assess the role of the basal ganglia in the internal generation of movements, we studied the activity of neurons in the head of the caudate and in the rostral putamen in relation to the execution of movements. Monkeys performed self-initiated and stimulus-triggered arm reaching movements in separate blocks of trials. With stimulus-triggered movements, 217 striatal neurons increased their activity after the trigger stimulus (127 in caudate, 90 in putamen). Of these, 68 neurons showed time-locked responses to the trigger stimulus, with a median latency of 60 ms, that were independent of visual or auditory stimulus modalities. Three quarters of responses were conditional on a movement being performed. These responses may participate in neuronal processes through which the reception of a stimulus is translated into the execution of a behavioral reaction. Further, 44 neurons increased their activity before the earliest muscle activity without being clearly time-locked to the stimulus (148-324 ms before movement onset), 55 neurons were activated later before the movement, and 50 neurons were activated after movement onset. With self-initiated movements, 106 striatal neurons showed movement-related activity beginning up to 460 ms before movement onset (52 in caudate, 54 in putamen). Comparisons between the two types of movement were made on 53 neurons with premovement activity beginning more than 500 ms before self-initiated movements. Only one fifth of them also showed movement-related activity with stimulus-triggered movements, including trigger responses. Comparisons among 39 neurons with movement-related activity during self-initiated arm movements showed that about half of them also showed movement-related activity with stimulus-triggered movements. These data demonstrate a considerably segregated population of striatal neurons engaged in the internal generation of movements, whereas processes underlying the execution of movements appear to involve overlapping neuronal populations.