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Control of 40-Hz firing of reticular thalamic cells by neurotransmitters.

This study bears on the control exerted by neurotransmitters on the expression of a 40-Hz pacemaker activity observed in reticular thalamic cells. Experiments were conducted in urethane-anaesthetized rats using extracellular recordings and local applications of antagonists against the neurotransmitters involved in the modulation of reticular thalamic cells. All drugs were dissolved in a Ringer's solution (pH 7.4) and were applied in small quantities (25-150 nl) by pressure through one barrel of a micropipette assembly. Forty-Hertz firing was abolished by local application of the alpha 1 antagonist prazosin and by bilateral lesion of the locus coeruleus. Local applications of glutamate antagonists reduced the rate of discharges by 30-50% as did cortical cooling or complete transection of the internal capsule. Conversely, scopolamine exerted a permissive action on the expression of 40-Hz activities; many spontaneously bursting units started firing at 40 Hz under the influence of this muscarinic antagonist. Since reticular thalamic cells are GABAergic and synaptically coupled via axonal collaterals, we investigated how GABAergic drugs affected the regular firing of these cells. Local applications of bicuculline produced a transient increase of the firing rates while the application of GABA induced intermittent pauses on a background of regular discharges. The application of piperidine-4-sulphonic acid, a GABAA receptor agonist, produced a similar effect. The length of pauses generated by piperidine was statistically analysed. It was found that the duration of short pauses was a multiple integer of the mean interspike interval of surrounding discharges. The preservation of the period and phase of the rhythm across the pauses implies that a subthreshold oscillation was presented into the cells during the arrests of discharges. Given the mode of action of noradrenaline and acetylcholine on reticular thalamic neurons, and considering a possible metabotropic action of glutamate, the above results suggest that deactivation of a leaky K conductance is critically involved in the regular firing of these cells in urethane-anaesthetized rats. Alternatively, because reticular cells are coupled via inhibitory synapses, it is proposed that the 40-Hz firing frequency reflects, in the frequency domain, a point of equilibrium in the reticular thalamic network when the leaky K conductance is fully deactivated by the metabotropic effects of monoamines and/or excitatory amino acids.

2-Amino-5-phosphonovalerate↗

Intrinsic and synaptically generated delta (1-4 Hz) rhythms in dorsal lateral geniculate neurons and their modulation by light-induced fast (30-70 Hz) events.

Thalamocortical neurons of cat dorsal lateral geniculate nucleus were recorded under urethane anesthesia. Neurons were identified by antidromic invasion from the internal capsule and by orthodromic stimulation from the optic chiasm or light stimuli. An intrinsic oscillation within the frequency of sleep delta waves (1-4 Hz) was induced by hyperpolarizing current pulses triggering a rhythmic sequence of low-threshold spikes alternating with after hyperpolarizing potentials. The increased propensity to oscillation after blockage of inputs arising in the retina indicates that afferent synaptic drives interfere with the intrinsic oscillation of lateral geniculate cells. The relatively rare occurrence of this type of oscillation in impaled neurons, as compared with extracellular recordings in the same nucleus or to intracellular recordings in other dorsal thalamic nuclei, suggests that the interplay between the two intrinsic currents generating delta oscillation is particularly critical in lateral geniculate cells. Another type of delta oscillation was characterized by excitatory postsynaptic potentials which gave rise to action potentials or to low-threshold spikes at more depolarized or hyperpolarized levels, respectively. It is suggested that this rhythm reflects synaptic coupling by intranuclear recurrent axonal collaterals. Light stimulation induced fast (30-70 Hz) excitatory events that were blocked after lidocaine injections into the eye. In all tested cells, changes in the ambient luminosity of the experimental room blocked the intrinsic as well as the synaptic oscillation within the delta frequency. In some cells, this suppressing effect was associated with depolarization and increased firing rate. These results demonstrate different types of sleep delta oscillations in visual thalamic neurons and show that they are modulated not only by brainstem regulatory systems, but also by specific drives along the visual channel.

Animals↗

Delta frequency (1-4 Hz) oscillations of perigeniculate thalamic neurons and their modulation by light.

Neurons in the perigeniculate sector of the reticular thalamic nuclear complex were recorded extra- and intracellularly under deep urethane anesthesia. They were identified by burst responses to optic chiasm stimulation and depolarizing spindle oscillations in response to internal capsule stimulation. Perigeniculate neurons displayed oscillations within the frequency range of electroencephalogram delta waves (1-4 Hz). One-third of extracellularly recorded neurons discharged rhythmic (2.5-4 Hz), high-frequency (150-200 Hz) spike bursts. This was similar to an intrinsic oscillation that was recently observed in dorsal lateral geniculate cells studied in vitro and in vivo. Other oscillating neurons displayed trains of single spikes (20-50 Hz) crowning rhythmic (2.5-4 Hz) depolarizing envelopes that were best expressed at the "resting" membrane potential (-60 to -65 mV). It is suggested that this oscillation reflects synaptic drives from dorsal lateral geniculate neurons. Changes in ambient room luminosity disrupted both types of delta rhythms. These data demonstrate for the first time that delta oscillations are present in the visual sector of the reticular thalamic nucleus. The results suggest that the two types of delta rhythmicity result from intrinsic and network properties of visual thalamic neurons and that perigeniculate cells may synchronize, through backward connections, the activity of dorsal lateral geniculate cells during deep stages of resting sleep.

Animals↗

Morphology of intracellularly stained spiny neurons in rat striatal grafts.

Two to six months after implantation of fetal striatal primordia into the kainic acid-lesioned neostriatum of adult rats, spiny neurons in the grafts were stained intracellularly with biocytin. To determine whether the spiny neurons in the grafts differentiate morphologically as in the host neostriatum, the intracellularly stained spiny neurons in the grafts were studied with light and electron microscopy and compared with that of spiny neurons in the host neostriatum. The spiny neurons in the grafts had ovoid or polygonal cell bodies with dendrites radiating in all directions. The somata were smooth and the dendrites, except for their most proximal portions, were rich in spines. All these features resembled the appearance of spiny neurons in the intact neostriatum. However, quantitative studies showed that the somata of spiny neurons in the grafts were larger than those in the host neostriatum (projected cross-sectional areas of 230 +/- 64.6 microns 2 in the grafts and 158 +/- 28.9 microns 2 in the host) and the spine density of graft neurons was lower than that of host neurons. Cells near the border of the grafts had dendrites extending both into the graft and into the host neostriatum. In these cells, the dendrites in the grafts had fewer spines than the dendrites in the host tissue. The axons of spiny neurons in the grafts had very large and dense intrastriatal collateral arborizations, which occupied a much larger volume than that of the dendritic domain of the parent cells. The local axonal arborizations of each of these cells filled almost the entire graft. In some cells, axonal branches were traced outside the grafts and were seen to enter the internal capsule fascicles. Unlike spiny neurons in the normal adult neostriatum, the spiny cells of the graft could have nuclear indentations. With this exception, the ultrastructural features of spiny neurons in the grafts were very similar to those in the hosts. Many unlabeled boutons made synapses on identified spiny neurons in the grafts. Terminals with small round vesicles made synaptic contacts on dendritic shafts and dendritic spines, while terminals with flattened or pleomorphic vesicles contacted somata, dendrites, and dendritic spines. Labeled axon collaterals of graft neurons made symmetrical synapses on somata, dendrites and spines in the grafts and in the host neostriatum. In the grafts, more than 60% of the axon terminals contacted dendritic shafts. The proportion of axosomatic and axospinous synapses varied substantially from cell to cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Topographical organization of the sources of discrete cortical projections within the striatum as determined by a retrograde fluorescence tracing technique in the cat.

The projections from the neostriatum and the paleostriatum to the cerebral cortex in the cat were examined by means of retrogradely transported fluorescent tracers primuline, Fast Blue, Nuclear Yellow and Evans Blue injected into different neocortical fields. In all cases after dye injections only large labelled cells of sources of striatocortical ipsilateral projections were observed. The main projections from the caudate nucleus and the putamen are directed to the auditory and neighbouring "associative" cortex, and more numerous projections from the globus pallidus are addressed to the motor cortex. No sources of cortical projections within the entopeduncular nucleus were found. Simultaneous injections of Fast Blue and primuline into even closely located and tightly bound functional regions of parietal or temporal cortex failed to reveal double-labelled neurons in the caudate nucleus, internal capsule, putamen and globus pallidus. Thus, our findings on cats are consistent with recent studies on rats and monkeys that suggest that striatal neurons innervate relatively small, restricted fields of the neocortex. Again, the results show evidence for a significant contribution to cholinergic cortical innervation not only of magnocellular neurons of the basal forebrain but also of large neo- and paleostriatal cells.

Animals↗

Astrocytic messenger RNA responses to striatal deafferentation in male rat.

This investigation describes the schedule and regional distribution of astrocytic responses in striatum following deafferentation by unilateral frontal cortex ablation. In the ipsilateral deafferented striatum, glial fibrillary acidic protein and clusterin (sulfated glycoprotein-2) messengerRNA showed peak elevations by 10 days postlesioning (Northern blots). Vimentin messengerRNA responded faster, with a transient elevation by three days postlesioning. The messengerRNA for glial fibrillary acidic protein, clusterin and vimentin returned toward control levels by 27 days postlesioning. However, the neuronal marker growth-associated protein messengerRNA, was decreased at all postlesion times. By in situ hybridization, the increased glial fibrillary acidic protein messengerRNA and clusterin messengerRNA signals were localized mainly to the dorsal half of the ipsilateral deafferented striatum and followed the same schedule as found by Northern blots. Glial fibrillary acidic protein messengerRNA was widely diffused in the dorsal striatum and was excluded from fascicles of the internal capsule; a similar distribution was found for glial fibrillary acidic protein-immunopositive astrocytes. While clusterin messengerRNA signal showed a distinct clustering, its immunoreactivity appeared as deposits in the deafferented striatal neuropil; Western blots confirmed the immunocytochemical results. By in situ hybridization, vimentin messengerRNA was mostly localized to the cortical wound cavity dorsal to the deafferented striatum and overlapped the distribution of vimentin-immunopositive cells. These findings suggest a coordination of striatal astrocytic messengerRNA responses with the degeneration of corticostriatal afferents. We also compared these same parameters with those from published reports on the hippocampus after deafferenting lesions. Certain astrocyte molecular responses to deafferentation are detected about five days earlier in the hippocampus than in the striatum. This different schedule in response to decortication may pertain to differences in synaptic remodeling in the hippocampus vs striatum.

Animals↗

Comparison between normal developing striatum and developing striatal grafts using drug-induced Fos expression and neuron-specific enolase immunohistochemistry.

The cell-level functional maturation of cell suspension grafts from embryonic day 14-15 rat striatal primordia implanted unilaterally into ibotenic acid lesioned striata of adult female rats was studied from two days to 10 weeks post-grafting. The functional and morphological characteristics of the grafts were compared with those of adult grafts (one year after implantation), normal adult striata and postnatal developing striata (up to four weeks after birth). Serial sections were stained with Cresyl Violet and investigated immunohistochemically with antibodies against dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein (DARPP-32, as a striatal marker), tyrosine hydroxylase (as a marker of dopaminergic fibres), Fos protein (as a cell-level marker of functional dopaminergic host-graft interactions), and neuron-specific enolase (correlated to differentiation and functional maturation of neuronal cells). Selected sections were double-stained for DARPP-32 and either tyrosine hydroxylase, Fos or neuron-specific enolase. The rats used to study dopamine receptor-activated expression of Fos were killed 2 h after administration of either the dopamine-releasing agent D-amphetamine (5 mg/kg intraperitoneally) or the dopamine-receptor agonist apomorphine (0.25 mg/kg subcutaneously, at which dosage it is active only on supersensitive receptors of denervated neurons). In normally developing rats, amphetamine induced Fos expression in both the striatum and globus pallidus by two weeks after birth; by four weeks, the pattern of amphetamine-induced Fos immunoreactivity was similar to that observed in adults. In the globus pallidus of both two- and three-week-old rats, amphetamine induced greater expression of Fos than in adults. Apomorphine did not induce appreciable Fos activation in either the striatum or the globus pallidus at any stage of development. In striatal grafts, amphetamine induced Fos expression from three weeks after implantation onwards, and by five to 10 weeks post-grafting the pattern of Fos immunoreactivity was similar to that observed in adult grafts. However, apomorphine induced a considerable number of Fos-positive nuclei in striatal grafts at three and four weeks after grafting. Neuron-specific enolase immunoreactivity was moderate in normal adult striatum and very high in the adult globus pallidus, and mainly located in neuronal perikarya and processes. Before two weeks of age, most neuron-specific enolase immunoreactivity was observed in internal capsule fascicles and the striatal afferents. Between two and four weeks after birth, neuron-specific enolase immunoreactivity in striatal and globus pallidus neurons gradually increased, while that in afferent fibres decreased to adult levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Immunohistochemical detection of thrombospondin in microglia in the developing rat brain.

The development of microglia involves the expression of a phenotype displaying phagocytic behaviour termed brain macrophage or amoeboid microglial cell. We have previously shown that rat brain macrophages purified in vitro secrete thrombospondin, an extracellular matrix protein, which acts on cultured neuronal cells by promoting neurite growth. In the present study, the expression of thrombospondin was investigated in tissue sections of the developing rat forebrain in relation to the distribution of microglia. These cells were identified using anti-macrophage antibodies and the isolectin B4 from Bandeiraea simplicifolia. Immunocytochemical detection of thrombospondin clearly outlined a cell population displaying the morphologies and distribution of brain macrophages, from the 17th day of embryonic life up to the end of the second postnatal week. These cells were most numerous in cortical and subcortical regions of developing fibre tracts such as the corpus callosum or the internal capsule. The localization of thrombospondin in brain macrophages was confirmed by double immunostaining using ED1 monoclonal anti-macrophage antibodies. Ramified microglial cells were also labelled transiently by anti-thrombospondin antibodies during early postnatal life. These results provide in situ evidence supporting the notion that microglial cells could favour axonal growth by producing thrombospondin during development.

Aging↗

Minimosymptomatic occlusion of the middle cerebral artery.

Minimosymptomatic occlusion of the MCA before the origin of the perforating branches is an exceedingly rare occurrence. We report two cases of MCA occlusion at its origin, the second case proven by the CT scan in vivo. Published work rules out the possibility of a functionally effective deep collateral circulation in the distribution of the capsular rami of the MCA. In view of this we argue that there may be cases - admittedly very rare - in which, given the individual variability of the vascular supply, the MCA may be of negligible functional importance to the circulation of the internal capsule. In such cases occlusion of the MCA would be relatively well tolerated.

Adult↗

The lazaroid U74389G protects normal brain from stereotactic radiosurgery-induced radiation injury.

PURPOSE: To test an established model of stereotactic radiosurgery-induced radiation injury with pretreatments of either methylprednisolone or the lazaroid U74389G. METHODS AND MATERIALS: Nine cats received stereotactic radiosurgery with a linear accelerator using and animal radiosurgery device. Each received a dose of 125.0 Gy prescribed to the 84% isodose shell to the anterior limb of the right internal capsule. One animal received no pretreatment, two received citrate vehicle, three received 30 mg/kg of methylprednisolone, and three received 5 mg/kg of U74389G. After irradiation, the animals had frequent neurologic examinations, and neurologic deficits developed in all of them. Six months after the radiation treatment, the animals were anesthetized, and had gadolinium-enhanced magnetic resonance (MR) scans, followed by Evans blue dye perfusion, euthanasia, and brain fixation. RESULTS: Magnetic resonance scans revealed a decrease in the size of the lesions from a mean volume of 0.45 +/- 0.06 cm(3) in the control, vehicle-treated, and methylpredniosolone-treated animals to 0.22 +/- 0.14 cm(3) in the U74389G-treated group. The scans also suggested the absence of necrosis and ventricular dilatation in the lazaroid-treated group. Gross pathology revealed that lesions produced in the untreated, vehicle-treated, and methylprednisolone-treated cats were similar and were characterized by a peripheral zone of Evans blue dye staining with a central zone of a mature coagulative necrosis and focal hemorrhage. However, in the U74389G-treated animals, the lesions were found to have an area of Evans blue dye staining, but lacked discrete areas of necrosis and hemorrhage. CONCLUSION: These results suggest that the lazaroid U74389G protects the normal brain from radiation injury produced by stereotactic radiosurgery.

Animals↗

Neuronal distribution in caudate nucleus and reticular-caudate pathways.

Methods of quantitative stereology are employed to determine the cell body diameters and the disposition of the neurons of caudate nucleus (CN) of the cat. Large neurons are more frequent in the infero-external region in a well defined zone 16 to 18 mm ahead of the interaural plane. Silver impregnations and electron microscopy after lesions in the ponto-mesencephalic reticular formation demonstrate its direct projections on the nucleus centralis medialis thalami and on the CN. Ascending fibers run along the ventral and lateral surfaces of the thalamus, some of them penetrate to the lamina medullaris medialis making contact in intralaminar nuclei and in the nucleus centralis medialis, others continue through the internal capsule to end in the infero-external region of the CN. The reticular formation of one side projects to both CN.

Animals↗

Afferent connections to the lateral hypothalamus: a horseradish peroxidase study in the rat.

Horseradish peroxidase, 13% Sigma Type VI, was administered iontophoretically to the mid lateral hypothalamus (LH) of male hooded rats. Animals were perfused intracardially on the following day and brains were removed and sliced in the coronal or sagittal planes into 30-50 micrometer sections. Sections were processed with DAB and BDH for the brown and blue reaction products and later examined by bright and dark field microscopy for the presence and location of retrogradely labeled neurons. Results indicate that a significant number of afferent connections to the LH originate in the olfactory and accumbens nuclei, pyriform cortex, olfactory tracts, magnocellular and medial preoptic and anterior hypothalamic regions, stria terminalis, stria hypothalamic tract, diagonal tract of Broca, caudate-putamen and globus pallidus, internal capsule, lateral septal nuclei, lateral preoptic area and anterior medial forebrain bundle, the various amygdaloid nuclei, zona incerta, perifornical region, dorsal and ventral medial hypothalamic areas, supraoptic, paraventricular and periventricular nuclei, posterior hypothalamus and medial forebrain bundle, ventral thalamic nuclei, the fields of Forel, arcuate and mammillary nuclei, adjacent to the fasciculus retroflexus, in the ventral tegmental area of Tsai, interpeduncular nucleus, substantia nigra, mesencephalic reticular formation, periaqueductal gray, locus coeruleus and parabrachial region. Results are discussed in terms of previous anatomical and neurophysiological data, probable pathways, and the function of LH neurons.

Afferent Pathways↗

Neurons of the bed nucleus of the stria terminalis: a golgi study in the rat.

Neuronal morphology in the bed nucleus of the stria terminalis (BST) was studied using Golgi techniques. The principal neurons of the lateral subdivision of BST have ovoid perikarya and 4-5 dendrites that branch several times and exhibit a dense covering of spines. Adjacent to the internal capsule is a small region, termed the "juxtacapsular subdivision" of BST, that consists of small, spiny cells. Neurons of the medial subdivision of BST have ovoid perikarya and 2-3 dendrites that branch sparingly. Dendritic spine density varies from sparse to moderate. Dendrites in the dorsocaudal portion of the medial subdivision extend into a cell-sparse zone adjacent to the lateral ventricle. Cells in the lateral portion of the preoptic continuation of BST have dendrites oriented perpendicular to fibers of the stria terminalis which traverse this area while medially located cells are oriented parallel to fibers of the stria. Axons of BST neurons emit collaterals that arborize modestly near the cell of origin. Neurons in the lateral and medial subdivisions of BST resemble, respectively, cells in the lateral and medial subdivisions of the central amygdaloid nucleus. Neurons in the juxtacapsular subdivision of BST are similar to neurons of the intercalated masses of the amygdala.

Animals↗

Lever pressing and active avoidance conditioning after electrolytic lesions of the entopeduncular nucleus in cats.

Several authors have shown that CN participates in the acquisition of motor conditioned responses (MCR), probably as the integrating structure. Most of CN's efferent fibers in the cat end in the entopeduncular nucleus (EPN), therefore the command for the motor pattern could be exerted through EPN, representing part of the efferent link of the neuronal circuitry involved in MCR. Thirty-two cats were trained to avoid actively an electrical stimulus when a series of flashes appeared, and to press a lever to obtain 0.5 ml of milk. After the cats reached the learning criterion for both responses, electrolytic lesions of the entopeduncular nucleus or internal capsule (IC) were made bilaterally. When the cats recovered their normal motor behavior, the conditioned sessions were resumed once a day, for 45-50 days. Both learning responses disappeared (p less than 0.01) in those animals with the largest EPN lesions. In contrast, for small EPN lesions, learned responses were absent only during the first 3 or 4 sessions, and then the level of responses increased each day. However, it never reached that of sham lesioned cats. On the other hand, IC lesioned cats showed no statistical differences with respect to sham lesioned animals. These data support the participation of EPN in the motor circuitry responsible for MCR.

Animals↗

MPTP, impairment of motor performance and amine accumulation in Macaca fascicularis.

The selective neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected (IV) into monkeys (Macaca fascicularis) in two different injection regimes. With the small dose regime, one monkey was injected with 0.25 mg/kg, every other day, over a 16 day period. In the large dose regime, another monkey was injected with 0.5 mg/kg every other day, over an 8 day period. While the time required for drug delivery was varied between animals, the total dose delivered was 2 mg/kg in both animals. Before, during and for 14 days after the course of drug administration both animals were assessed on several motor function tests. The animal receiving the small dose regime showed normal motor performance on all tests for the duration of the study, however, the monkey receiving the large dose regime displayed progressive akinesia, muscular rigidity, and aphagia. In fact, impairment was so severe that this animal had to be force fed and maintained with daily oral L-dopa. Fluorescent histochemical assessment of forebrain in both monkeys revealed that striatal tissue was totally devoid of fluorescence in both cases. Large, swollen axons in the internal capsule, hypothalamus and midbrain were visible only in the severely impaired animal. These results suggest that, as with other neurotoxins, degeneration associated increases in amines may be important in the aetiology of Parkinson-like motor impairment produced by selective neurotoxins.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Behavioral demonstration of a reciprocal interaction between dopamine receptor subtypes in the mouse striatum: possible involvement of the striato-nigral pathway.

It is well known that stimulation of the D-2 dopamine receptor in vitro inhibits the increased efflux of cyclic adenosine monophosphate caused by D-1 receptor agonists. Furthermore, behavioral data suggest that the striato-nigral pathway is more involved with the dopamine agonist-induced expression of oral behaviors, which are, in turn, mediated by stimulation of the D-1 receptor. We examined an in vivo model to determine whether this D-1/D-2 reciprocal interaction is detectable at a behavioral level. First, mice were pretreated with wide range of doses of the D-2 antagonist, spiperone, and then injected with a behaviorally active dose of apomorphine (a nonspecific direct dopamine agonist) and were observed for incidence of oral behavior and rated for stereotypic behavior. A biphasic effect of spiperone pretreatment was observed, at some low doses both stereotypy and oral behavior were enhanced, while at high doses, both agonist-induced behaviors were progressively inhibited. To test the specificity of this effect for the striato-nigral pathway, mice were administered discrete electrolytic lesions in the ventral portion of the internal capsule in one hemisphere. The animals that responded to apomorphine by rotating ipsilaterally to the lesion were used in two, five-point apomorphine dose-response curves, one with, and one without, pretreatment with the dose of spiperone which most enhanced stereotypic behavior and incidence of oral behavior. The spiperone pretreatment caused a clear increase in the maximum rotational response to apomorphine without affecting the ED50. These data suggest that behavior associated with the striato-nigral efferent from striatum is marked by the opposition of D-1 and D-2 receptors.

Animals↗

Localization of a novel pathway for the liberation of GABA in the human CNS.

Serum carnosinase is a dipeptidase, which is synthesized in human brain, where it hydrolyzes homocarnosine to release free GABA. Immunohistochemical procedures were used to demonstrate the presence of this enzyme in several layers of the retina and in certain neuronal tracts of the cerebral cortex, cerebellar cortex, olfactory bulb, hippocampus, and in disseminated tracts presumably from the internal capsule, interspersed among the basal ganglia. The enzyme was also present in the epithelial cells of the choroid plexus and in corpora amylacea, which were seen in many regions of the CNS. Homocarnosine was localized either in the same tracts or in nearby neurons. For example, the Purkinje cells of the cerebellar cortex contained homocarnosine, whereas serum carnosinase was localized in adjacent neuronal projections apparently originating from outside the cerebellar cortex and having probable synaptic contact with the Purkinje cells. These findings suggest that in addition to glutamate decarboxylation, a second metabolic reaction for the formation of free GABA exists in specific neuronal tracts of the human CNS where GABA is released from homocarnosine by the action of serum carnosinase.

Animals↗

Substantia nigra opiate receptors on basal ganglia efferents.

Many behavioral effects of opiate narcotics and peptides have been linked to effects on dopamine neurons originating in the substantia nigra pars compacta and ventral tegmental area. Selective brain lesions were combined with quantitative autoradiography to determine whether opiate receptors are on dopaminergic somata and/or processes in the substantia nigra pars compacta and ventral tegmental area. 6-Hydroxydopamine lesions that eliminated dopamine neurons produced little change in the pattern or density of [3H]-naloxone binding in the substantia nigra pars compacta or ventral tegmental area. Radiofrequency lesions of the internal capsule or globus pallidus and kainic acid lesions of the striatum markedly decreased [3H]-naloxone binding in the pars compacta and pars reticulata. These results are consistent with a dense distribution of opiate receptors on pallido-nigral and/or striato-nigral fibers and strengthen the likelihood that local effects of opiates on dopamine function in the nigrostriatal pathway are mediated indirectly by actions on nondopaminergic processes.

Animals↗