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Latencies of visually guided saccades in unilateral hemispheric cerebral lesions.

Latencies of lateral visually guided saccades were studied in 60 patients without hemianopia who had unilateral focal lesions clearly visible on computed tomographic (CT) scan that were variously located in both cerebral hemispheres. Significantly asymmetrical latencies were found in 29 patients whose lesions had damaged the deep and posterior frontal region near the corpus callosum and/or, just inferior to this region, the anterior part of the internal capsule. In the 31 other patients, including those with lesions of the frontal eye fields (FEF), latencies were not significantly asymmetrical and the lesions spared the entire region just described. These topographical features suggest that the asymmetry of latencies is due to damage in a certain portion of the efferent pathways descending from the FEF. A significant increase in bilateral latency was observed in most patients whose lesions had damaged the posterior part of the parietal cortex and/or the underlying white matter. The parietal lobe could therefore exert an excitatory bilateral action on the triggering of visually guided saccades, probably mediated via the superior colliculus. A significant decrease in the bilateral or ipsilateral latency was often found in patients whose lesions had damaged the FEF or the underlying white matter. The frontal lobe could therefore exert a predominantly inhibitory bilateral action on this triggering, probably also mediated via the superior colliculus. However, an increase in contralateral latency in some patients with subcortical frontal lesions indicates that the FEF also probably have an excitatory action. This action could be transmitted directly (or indirectly via the superior colliculus) to the reticular premotor structures by tracts decussating partly through the corpus callosum.

Adult↗

Some aspects of the organization of the thalamic reticular complex.

Anatomical methods which depend upon the anterograde axonal transport of isotopically labeled neuronal proteins or the retrograde axonal transport of the enzyme, horseradish peroxidase, have been used to elucidate the relationships between the reticular complex and the dorsal thalamus and cerebral cortex. Injections of tritiated amino acids in the dorsal thalamus or cerebral cortex in rats, cats and monkeys, show that as the bundles of thalamo-cortical and cortico-thalamic fibers joining a particular dorsal thalamic nucleus to its associated area of the cerebral cortex traverse the reticular complex, they each give rise to a dense zone of terminals occupying a sector of the reticular complex which is relatively constant for that dorsal thalamic nucleus and cortical area. However, because of the wide extent of the dendritic fields of the reticular cells and the degree of overlap between the sectors of the complex subtended by adjacent dorsal thalamic nuclei and adjacent cortical areas, it is likely that the reticular complex samples thalamo-cortical and cortico-thalamic activity in a somewhat unspecific manner. Fibers passing to the reticular complex from the intralaminar nuclei of the thalamus appear to be associated with the projection from the intralaminar nuclei to the striatum. Injections of tritiated amino acids in the reticular complex itself and injections of horseradish peroxidase in various other parts of the brain show that the only efferent pathway from the reticular complex terminates in the nuclei of the dorsal thalamus. The reticular complex does not appear to send fibers to other components of the ventral thalamus nor to the cerebral cortex.

Animals↗

Postnatal maturation of subcortical projections from the prefrontal cortex in the rhesus monkey.

Orbital and dorsolateral prefrontal lesions were performed on a series of rhesus monkeys at 2, 6, or 24 months of age. The consequent degeneration in the efferent pathways from these cortical regions to the caudate nucleus, the dorsomedial nucleus of the thalamus and adjacent structures was studied at 5- and 15-day survival times by a modification of the Nauta-Gygax method for tracing degenerating fibers. Following dorsolateral lesions, considerable numbers of black-impregnated degenerating fibers were found in the parvocellular division of the dorsomedial nucleus and in the fiber bundles of the internal capsule and the subcallosal fasciculus at all ages.

Animals↗

Organization of the ascending projections from the ventral tegmental area: a multiple fluorescent retrograde tracer study in the rat.

The projections from the ventral tegmental area of Tsai (VTA) to the frontal cortex (FC), lateral septum (LS), were investigated in the rat by means of the double retrograde fluorescent tracer technique. True blue and fast blue were used in combination with nuclear yellow as retrograde tracers. After combined injections placed into two different terminal fields, many singly and some doubly labeled neurons were seen in the midbrain. In all cases the labeled cells were observed in the ipsilateral VTA, while after injections placed into the LS and Acc some fluorescent neurons were also seen in the contralateral VTA. The patterns of distribution of the labeled neurons showed a topographic organization of the VTA efferent pathways. However, some degree of overlapping was evident in the distribution of cells retrogradely labeled from different terminal fields. The number of the doubly labeled neurons varied according to the sites of combined injections, but in each experiment it never exceeded 10% of the total number of labeled perikarya. Doubly labeled neurons were particularly numerous after combined injections placed into the FC, LS, or LH; on the contrary, very few doubly labeled cells were observed after combined injections placed into the CPu and LS or LH. The organization of the ascending VTA projections suggests that they are probably integrated into different anatomical sets.

Afferent Pathways↗

Organization of corticogeniculate projections in the turtle, Pseudemys scripta.

The efferent pathways from the visual cortex to the dorsal lateral geniculate complex of turtles have been studied by using the orthograde and retrograde transport of horseradish peroxidase (HRP). Injections of HRP in the lateral thalamus retrogradely label neurons throughout the visual cortex. The majority of labeled neurons have somata in layer 2 of the lateral part of dorsal cortex (D2); a minority have somata in layer 3. Labeled neurons in layer 2 tend to have vertically oriented, fusiform somata and dendrites that ascend into layer 1. Labeled neurons in layer 3 have fusiform somata and dendrites, both oriented horizontally. Injections of HRP in visual cortex orthogradely label corticofugal axons. Those projecting to the lateral geniculate complex course laterally from the visual cortex, pass through the striatum (occasionally bearing varicosities), and enter the diencephalon in the ventral peduncle of the lateral forebrain bundle. Individual axons leave the ventral peduncle and run dorsally in the transverse plane, entering the dorsal lateral geniculate complex from its ventral edge. They continue dorsally, principally in the cell plate of the geniculate complex, where they bear varicosities.

Animals↗

Patterns of reciprocity in auditory thalamocortical and corticothalamic connections: study with horseradish peroxidase and autoradiographic methods in the rat medial geniculate body.

The patterns of reciprocity between retrogradely labeled thalamocortical cells of origin and anterogradely projecting corticothalamic axon terminals were studied in the subdivisions of the adult rat medial geniculate body following auditory cortical injections of mixtures of horseradish peroxidase and [3H]leucine. The labeling produced by each method was examined independently, both qualitatively and quantitatively, in adjacent series of tetramethylbenzidine-processed sections and in autoradiographs after 24-96 hour survivals. The distribution and number of labeled cells and axon terminals were assessed separately for each method and compared systematically throughout the rostro-caudal extent of the medial geniculate complex. The principal finding was that zones containing many retrogradely labeled neuronal somata are not completely coextensive with areas of heavy terminal labeling within the medial geniculate body, although there is a gross congruence of thalamocortical-corticothalamic projections. Conversely, we found many zones of autoradiographic silver grains without retrogradely labeled somata in the adjacent sections; in general, the autoradiographic zones of non-reciprocity were more extensive and marked than were retrograde zones of non-reciprocity. The rat medial geniculate complex could be subdivided on the basis of its neuronal organization, cytoarchitecture, fiber architecture, and thalamocortical and corticothalamic connections into three major parts: the ventral, dorsal, and medial divisions. This pattern of organization was comparable, though not identical, to that of the corresponding subdivisions in the cat medial geniculate body (Winer: Adv. Anat. Embryol. Cell Biol. 86:1-98, '85). While the retrograde labeling appeared to mark many of the different types of neurons in each of the three divisions, there were distinct local and quantitative and qualitative differences in the distribution of autoradiographic terminal labeling. The ventral division received the heaviest cortical input, the medial division the least labeling, while the dorsal division was intermediate. Thus, corticogeniculate projections to the ventral division often produced values 20-100 times above background (absolute values: 2,001-10,000 silver grains/14,400 micron2; background: less than 100 silver grains/14,400 micron2); the same projection to the dorsal division usually resulted in grain counts no more than 5-20 times above background (501-2,000/14,400 micron2), while in the medial division the number of silver grains rarely exceeded two to five times the background (201-500/14,400 micron2).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Comparative ultrastructural localization of the NMDAR1 glutamate receptor in the rat basolateral amygdala and bed nucleus of the stria terminalis.

The N-methyl-D-aspartate (NMDA)-type glutamate receptor in the basolateral amygdala (BLA) has been implicated in activity-dependent plasticity important for cortically evoked acquisition of fear-potentiated startle response. We examined the ultrastructural immunoperoxidase labeling of the R1 subunit of the NMDA receptor in the BLA of adult rats to determine the potential cellular and subcellular sites mediating the effects generated by NMDA activation. The localization was compared with that seen in the bed nucleus of the stria terminalis (BNST), the major efferent pathway from the central nucleus of the amygdala, which has a more pronounced involvement in autonomic function. Electron microscopy established that in the BLA, 68.4% (n = 177) of the profiles showing NMDAR1-like immunoreactivity (NMDAR1-LI) were dendrites, and 19.8% were distal tips of astrocytic processes. In contrast, profiles containing NMDAR1-LI (n = 262) in the BNST were more equally distributed between dendrites (37.4%) and axons (38.2%). The subcellular localization of NMDAR1 immunoreactivity was, however, similar in both regions. Our findings provide the first ultrastructural evidence that glutamate may prominently act through NMDAR1 receptors to elicit postsynaptic actions on intrinsic neurons in the BLA and BNST. The results also indicate that, in the BLA, the NMDAR1 receptor plays an important role in astrocytic function, whereas the receptor is more preferentially a presynaptic modulator in axons which terminate in or pass through the BNST.

Amygdala↗

Striatal neurochemical changes in transgenic models of Huntington's disease.

Transgenic mouse models of Huntington's disease (HD) were examined following the onset of overt behavioral symptoms. The HD transgenic mice demonstrated profound striatal losses in D1, D2, and D3 dopamine (DA) receptor proteins in comparison with their nonsymptomatic, age-matched littermate controls. In parallel, a robust increase in the striatal D5 DA receptor subtype occurred in the transgenic compared with the wild-type control mice. This receptor elevation was accompanied by heightened cyclic AMP levels, which may be induced by the adenylyl cyclase-linked D5 receptor. This is a unique result; normal striatal D5 protein levels are modest and not thought to contribute substantially to cyclic AMP-mediated DA signaling mechanisms. Simple compensatory up-regulation of D5 DA receptors in response to D1 receptor subtype loss does not explain our findings, because genetic inactivation of the D1 DA receptor does not alter levels of D5 DA receptor expression. Immunofluorescent detection of tyrosine hydroxylase showed that nigrostriatal DA containing terminals were reduced, further supporting that disturbances in DA signaling occurred in HD transgenic models. The substance P-containing striatal efferent pathway was more resistant to the HD mutation than met-enkephalin-producing striatal projection neurons in the transgenics, based on neuropeptide immunofluorescent staining. Analogous findings in multiple transgenic models suggest that these changes are due to the presence of the transgene and are not dependent on its composition, promotor elements, or mouse strain background. These findings suggest modifications in the striatal DA system and that its downstream signaling through cyclic AMP mechanisms is disrupted severely in HD following onset of motor symptoms.

Animals↗

Resurgence of functional neurosurgery for Parkinson's disease: a historical perspective.

The history of functional neurosurgery for the treatment of Parkinson's disease is reviewed. Two major stages may be distinguished: (1) open functional neurosurgery, which started in 1921 with bilateral cervical rhizotomy by Leriche. In 1937 Bucy performed the first motor cortectomy in a tremor patient, and subsequently introduced lesioning of the corticospinal tract at different levels. In 1939 Meyers started open transventricular surgery of the basal ganglia, which was abandoned in the 1940s because of high mortality. However, this operation drew attention to the basal ganglia and their efferent pathways as surgical targets for the relief of parkinsonian symptoms. (2) Stereotactic (closed) functional neurosurgery in patients was in 1947 for the first time performed by Spiegel and Wycis, soon followed by surgeons in various countries. Originally, the globus pallidus and the ansa lenticularis were the surgical targets but were replaced at the end of the 1950s by the ventrolateral thalamus. A few surgeons positioned their lesions in the subthalamic area. In both targets favorable results were reported for the treatment of tremor and rigidity with acceptable adverse events. In selected patients, bilateral surgery was performed. In 1969 the results of more than 37,000 stereotactic operations had been published. Criteria for the surgical technique and selection of patients were described, and various stereotaxic atlases became available. At that time, L-dopa became generally available and the number of stereotactic operations declined dramatically. However, as a result of the shortcomings of the L-dopa therapy in the long-term treatment of Parkinson's disease, the thalamotomy gradually regained its place. New developments were the reintroduction of the pallidotomy by Laitinen in 1992 and the thalamic stimulation for pharmacotherapy-resistant tremor by Benabid and collaborators in 1991. New insights in the pathophysiology of Parkinson's disease supported the revival of the functional stereotactic neurosurgery and recently caused the introduction of the subthalamic nucleus as a surgical target in the treatment of Parkinson's disease.

History, 18th Century↗

Brainstem reflexes: electrodiagnostic techniques, physiology, normative data, and clinical applications.

An overview is provided on the physiological aspects of the brainstem reflexes as they can be examined by use of clinically applicable neurophysiological tests. Brainstem reflex studies provide important information about the afferent and efferent pathways and are excellent physiological tools for the assessment of cranial nerve nuclei and the functional integrity of suprasegmental structures. In this review, the blink reflex after trigeminal and nontrigeminal inputs, corneal reflex, levator palpebrae inhibitory reflex, jaw jerk, masseter inhibitory reflex, and corneomandibular reflex are discussed. Following description of the recording technique, physiology, central pathways, and normative data of these reflexes, including an account of the recording of recovery curves, the application of these reflexes is reviewed in patients with various neurological abnormalities, including trigeminal pain and neuralgia, facial neuropathy, and brainstem and hemispherical lesions. Finally, simultaneous electromyographic recording from the orbicularis oculi and the levator palpebrae muscles is discussed briefly in different eyelid movement disorders.

Blinking↗

Subthalamic nucleus lesions alter basal and dopamine agonist stimulated electrophysiological output from the rat basal ganglia.

The subthalamic nucleus (STN) is an important link in the "indirect" striatal efferent pathway. To assess its role on basal ganglia output via the substantia nigra pars reticulata (SNr), we monitored the single unit activities of SNr neurons in chloral hydrate-anesthetized rats 5-8 days after bilateral kainic acid lesions (0.75 microg/0.3 microl/side) of the STN. Consistent with loss of an excitatory input, the average basal firing rate of SNr neurons was significantly reduced in STN-lesioned animals. Moreover, the lesions modified the responses of SNr neurons to individual and concurrent stimulation of striatal D1 and D2 receptors. Bilateral striatal infusions of the D1/D2 agonist apomorphine (10 microg/microl/side) into the ventral-lateral striatum (VLS) were previously shown to cause significant increases in SNr cell firing (to 133% of baseline) in normal rats. However, in STN-lesioned rats, identical infusions caused no overall change in SNr activity (mean, 103% of basal rates). Conversely, selective stimulation of striatal D2 receptors by bilateral co-infusion of the D2 agonist quinpirole and the D1 antagonist SCH 23390 that previously caused little change in SNr firing in normal rats significantly inhibited their firing in STN-lesioned rats. Finally, the modest excitatory responses of SNr neurons to selective stimulation of striatal D1 receptors by co-infusions of SKF 82958 with the D2 antagonist YM09151-2 were not altered by lesions of the STN. These results implicate the STN as a mediator of excitatory response of SNr neurons to D2, and mixed D1/D2, dopamine receptor agonists in normal rats, and challenge conventional views on the role of the STN and the "indirect" pathway in regulating dopamine-stimulated output from the SNr.

Action Potentials↗

Withdrawal following cocaine self-administration decreases regional cerebral metabolic rate in critical brain reward regions.

The quantitative [14C]-2-deoxyglucose autoradiographic method was utilized to assess regional cerebral metabolic rate for glucose (rCMRglc) in rat brain during withdrawal from cocaine self-administration. RCMRglc was determined in 62 regions from brains of naive rats which were placed into an empty operant chamber for 12 hr continuously, and rats trained to self-administer cocaine during 3 hr training sessions and subsequently placed into the operant chamber for 12 hr continuously with or without access to cocaine. Animals placed into the chamber without access to cocaine were examined 6 hr later, while animals allowed access to the 12 hr cocaine binge were examined either 6 or 72 hr post-cocaine. Metabolic activity was reduced during withdrawal in the nucleus accumbens, olfactory tubercle, islands of Calleja region, basolateral and central amygdaloid nuclei, medial septum, piriform and cingulate cortices, rostral caudatoputamen, entopeduncular nucleus and the adjacent lateral hypothalamus, somatosensory, auditory, and motor cortices compared to the naive state. These effects were usually more severe at 72 than at 6 hr after binge exposure, with intermediate values observed in cocaine trained animals without binge exposure. The response was negatively correlated with the amount of cocaine consumed during binge exposure in the striatum, olfactory tubercle, piriform, cingulate, somatosensory, and motor cortices. Thus, the amount of cocaine consumed can affect the extent of metabolic depression after sustained drug exposure. The pattern of regional effects suggests that mesolimbic and rostral extrapyramidal dopamine terminal regions and certain of their efferent pathways are preferentially affected during cocaine withdrawal. The reduction of basal metabolic rate observed in these brain regions during cocaine withdrawal may become more severe with time despite the apparent recovery of certain behavioral-motivational responses.

Animals↗

Capsaicin-sensitive afferents and blood pressure regulation during pentobarbital anaesthesia in the rat.

(1) Maintenance of blood pressure was investigated during induction of pentobarbital anaesthesia in rats after elimination of capsaicin-sensitive afferent neurons (capsaicin-denervated rats) as compared to vehicle-treated controls. The catecholamine content of heart and adrenals and the rise in blood pressure following electrical excitation of the spinal adrenergic nerves (pithed rat preparation) was also compared between both groups. (2) Capsaicin-denervated rats and their controls had equal amounts of catecholamines in heart and adrenals as well as equal pressor responses to electrical stimulation of spinal sympathetic nerves, thus excluding an influence of capsaicin on efferent pathways. In the state of consciousness, both groups showed the same blood pressure. (3) In capsaicin-denervated rats and in their controls, pentobarbital-induced anaesthesia (50 mg/kg i.p.) was characterized by a decline in blood pressure during the first 6 min. In the controls, this fall in blood pressure was followed by a slow compensatory rise to a level slightly higher than before anaesthesia, and this level was maintained during the following 60 min. This compensation was completely absent in capsaicin-denervated rats, indicating a role for capsaicin-sensitive nerves in this mechanism. An injection of pentobarbital (50 mg/kg i.p.) in pithed rats reduced the pressor response to electrical stimulation of spinal sympathetic nerves by about 40% in capsaicindenervated rats and in their controls. This inhibitory effect of pentobarbital might be involved in the initial fall in blood pressure in intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Neursecretory fibres in the median eyes of the scorpion, Androctonus australis L.

The retina of the median eyes of the North African scorpion, Androctonus australis L., is supplied with numerous neurosecretory nerve fibres which establish synaptoid contacts on the retinula cells. The number of fibres or profiles of varicosities of fibre terminals associated with a retinular unit (five retinula cells with a fused rhabdom) varies between 10 and 20. Electron-opaque vesicles with a diameter of 80-100 nm are abundant within the axonal profiles. The synaptoid junctions are characterized by postsynaptic electron-dense material on the inner leaflet of the retinula cell membrane and, frequently, presynaptic submembranous dense material. Because of these ultrastructural features, the junctions observed here resemble typical interneuronal synaptic contacts. Hence this kind of neurosecretory junction appears to be unique among arthropods. It is suggested that the neurosecretory fibres within the retina represent the efferent pathways for the control of the circadian pigment movements within the retinula cells.

Animals↗

Inhibitory modulation of the cardiovascular defence response by the ventrolateral periaqueductal grey matter in rats.

In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the dorsal periaqueductal grey matter (PAG) evoked a pressor response with tachycardia, vasodilatation in the hindlimb and hyperpnoea: a pattern of response known as the defence reaction. Microinjection of the synaptic excitant, D,L-homocysteic acid (DLH), but not saline, into the ventrolateral PAG at the level of the decussation of the superior cerebellar peduncle (approximately 7.3-8.3 mm caudal to bregma) produced a reduction in the size of the cardiovascular components of the defence reaction evoked by electrical stimulation in the dorsal PAG. Injections of DLH made outside this region had no effect on the defence response. Injection of DLH into the "defence inhibition area" had no effect on the pressor response evoked distally in the efferent pathway for the defence reaction, by electrical stimulation in the rostral ventrolateral medulla (RVLM). Activation of neurones in a restricted portion of the caudal ventrolateral PAG appears to modulate activity in the descending pathway for the defence response evoked from the dorsal PAG. It is argued that the inhibitory interaction probably occurs at the level of synapses in the RVLM.

Animals↗

Hippocampal neurons transplanted into ischemically lesioned hippocampus: electroresponsiveness and reestablishment of circuitries.

Severe forebrain ischemia was used to damage selectively the CA1 region of the rat hippocampal formation. One week later the CA1 region was repopulated with suspensions of 18 day old fetal hippocampal tissue. Intracellular recordings were made from single units within the transplants by using the "in vitro" slice preparation, two to nine months following transplantation. Based on firing characteristics during depolarizing current injection, pyramidal-like and interneuron-like cells were identified within the transplants. Synaptic potentials could be evoked in the pyramidal-like neurons by stratum radiatum and stratum oriens stimulation demonstrating that normal afferent contacts had been made. Local inhibitory circuits were not obvious within the transplanted regions as demonstrated by prolonged EPSP's and the absence of early or late after-hyperpolarization. This was supported by the lack of conductance fluctuation in the active membrane when compared with the resting cell. Antidromic spikes could be evoked by applying shocks to the stratum oriens, towards the fimbria and subiculum, suggesting that the transplanted neurons were projecting basal neurites, quite long distances, along the normal efferent pathways. Thus, the transplanted neurons have the capacity to reconstruct damaged circuitries and develop intrinsic properties similar to their normal counterparts.

Action Potentials↗

The influence of acute and chronic cervical sympathectomy on the ocular hypotensive effect of clonidine.

The influence of clonidine on intraocular pressure was studied in chloralose-anesthetized cats. The cats were subjected to unilateral cervical sympathectomy, either acute or chronic. The drug was injected either intravenously or into the left vertebral artery. With the aim of investigating the role of the sympathetic nervous system in the central IOP-lowering effect of clonidine, the fall in IOP induced by the drug in these preparations was compared to the decrease in ocular pressure caused by clonidine in intact cats. An enhanced depressor effect in both eyes of unilaterally sympathectomized cats became evident after the intravenous injection of clonidine. In contrast, the effect of central administration was similar or even smaller than in intact cats. We conclude that the central IOP-lowering effect of clonidine is diminished after cervical sympathectomy, indicating that the peripheral sympathetic nervous system is the efferent pathway of this centrally initiated effect.

Animals↗

Modification of the behavioural effects of amphetamine by a GABA agonist in a primate species.

Acute administration of d-amphetamine in the marmoset results in a dose dependent increase in small head movements (checking), and an almost total suppression of purposeful activities and social interaction. It has little effect on locomotion and does not induce stereotyped gnawing. The GABA-agonist, muscimol, decreases checking, locomotion, activities and social interaction when given alone, but induces jerking movements at large doses. When administered in combination with amphetamine, muscimol induces persistent stereotyped gnawing. On the basis of the present findings and those of experiments in rodents it is suggested that compulsive gnawing results from overactivity in the striatal efferent pathway, while checking is probably mediated by extra-striatal sites. Since the behavioural effects of muscimol resemble those of the typical neuroleptics with the exception of the induction of gnawing, it is suggested that muscimol, though sedative, may counteract certain extrapyramidal effects of neuroleptic treatment while facilitating their other behavioural effects.

Animals↗