Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Subthalamic Nucleus”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources

A hypothesis on the pathophysiological mechanisms that underlie levodopa- or dopamine agonist-induced dyskinesia in Parkinson's disease: implications for future strategies in treatment.

Long-term treatment of human Parkinson's disease with levodopa or dopamine agonists is often complicated by the appearance of abnormal involuntary movements (dyskinesias) that are extremely difficult to control. Little is known of the cause, pathophysiological mechanisms, or possible strategies for amelioration of this manifestation of dyskinesia. A hypothesis is set forth on the neural mechanisms that mediate levodopa- or dopamine agonist-induced dyskinesia (in particular chorea) as a side effect of the treatment of parkinsonism. Evidence is drawn from both clinical observations and experimental studies in a spectrum of movement disorders ranging from ballism through chorea to parkinsonism. It is proposed that (a) All forms of chorea, whatever their origin, share a common underlying neural mechanism. (b) Disordered activity of the subthalamic nucleus is central to the generation of choreic movements. In levodopa- or dopamine agonist-induced dyskinesia, (c) The site of action of dopaminergic agents in causing chorea is the putamen. (d) The specific pathophysiological state conducive to the appearance of chorea is brought about by the long-term exposure of the dopamine-depleted (parkinsonian) putamen to exogenous dopaminergic agents. (e) Long-term exposure to dopaminergic agents causes (either directly or indirectly) preferential inhibition of the subpopulation of putaminal neurones that project specifically to the lateral segment of the globus pallidus. This causes disinhibition of lateral pallidal neurones, which become overactive and physiologically inhibit the subthalamic nucleus. (f) The hypothesis suggests a number of possible strategies that might be useful for the alleviation of levodopa-induced dyskinesia.

Brain↗

Mapping of the motor pathways in rats: c-fos induction by intracortical microstimulation of the motor cortex correlated with efferent connectivity of the site of cortical stimulation.

The general goal of the present study was to investigate structural components of a neural system anatomically as well as functionally. The rat motor system, which is reasonably well understood, was selected and a new procedure was developed to combine a functional marker with axonal tracing methods (in the same animal). This was achieved by mapping c-fos induction immunocytochemically as a result of intracortical microstimulation in the distal forelimb area of the motor cortex. The anterograde tracers Phaseolus vulgaris-leucoagglutinin or biocytin were deposited at the site of intracortical microstimulation, the former three weeks and the latter two to three days before stimulation. Neuronal nuclei, labeled for the expressed c-fos protein, were present and mapped in the following structures: motor cortex; basal ganglia (caudate-putamen, globus pallidus); thalamus (reticular, ventromedial and posterior nuclei); subthalamic nucleus; substantia nigra; tectum; red nucleus; pontine nuclei; inferior olive; external cuneate nucleus; cerebellar cortex; deep cerebellar nuclei. Labeling was often bilateral but generally more substantial ipsilaterally, except in the cerebellum where it was mainly contralateral. Axonal labeling, including terminal branches and boutons, was also found in most of the above structures with the exception of the globus pallidus, deep cerebellar nuclei, cerebellar cortex and external cuneate nucleus. These expected exceptions demonstrate that activity changes in these latter structures, as revealed by c-fos labeled neurons, were induced over more than one synapse. This combined procedure might, therefore, be useful in deciding whether two structures in a given system are linked directly (monosynaptically) or indirectly (polysynaptically) to each other. In contrast to the 2-deoxyglucose technique, functional mapping by means of c-fos induction provides cellular resolution, making it possible to establish fine details of axonal contacts with target neurons: boutons in close apposition to c-fos labeled neurons were clearly observed here, for instance in the cerebral cortex, caudate-putamen, thalamus, subthalamic nucleus and pontine nuclei. Surprisingly, the ventrolateral and ventrobasalis nuclei of the thalamus contained numerous and dense axon terminals labeled with Phaseolus vulgaris-leucoagglutinin or biocytin, but the contacted neurons in the ventrolateral and ventrobasalis nuclei were not marked with c-fos. However, with respect to directly connected structures, there was, in general, a good correlation between structures with axonal labeling and those with c-fos labeled neurons.

Animals↗

Pathological correlates of extrapyramidal signs in Alzheimer's disease.

Extrapyramidal signs frequently accompany Alzheimer's disease (AD), but the pathological substrate remains unknown. Clinical and postmortem information from patients with AD, Parkinson's disease, or progressive supranuclear palsy and control subjects seen at a large tertiary medical center between 1989 and 1994 was examined. AD patients who had taken neuroleptics and AD brains that also contained Lewy bodies were excluded. The presence of extrapyramidal signs was determined using the Unified Parkinson's Disease Rating Scale. Sections of basal ganglia, subthalamic nucleus, and substantia nigra were examined for neurofibrillary tangles and neuropil threads and the nigra for neuronal numbers. Patients with AD (with or without extrapyramidal signs) did not show neuronal loss in the nigra compared to control subjects, while both Parkinson's disease and progressive supranuclear palsy brains showed marked depletion. The number of neurofibrillary tangles and neuropil threads was increased in AD (with or without extrapyramidal signs) nigra compared to control tissue, and also in progressive supranuclear palsy nigra, but not Parkinson's disease nigra. The numbers of nigral neurofibrillary tangles and neuropil threads were positively related to extrapyramidal signs in AD. There were no correlations between tangles and threads in the basal ganglia or subthalamic nucleus and extrapyramidal signs in AD. Thus, extrapyramidal signs in AD correlate best with tangle pathology in the nigra and do not require the concomitant presence of Lewy bodies.

Aged↗

M3 muscarinic receptors mediate cholinergic excitation of the spontaneous activity of subthalamic neurons in the rat.

The effect of the muscarinic antagonist on carbachol-induced increase in spontaneous activity of neurons of the subthalamic nucleus was examined by recording the extracellular unitary activity in an in vitro slice preparation. Carbachol produced (98% of the 263 neurons tested) an increase (twofold of the basal at 500 nM) of the discharge frequency. The EC50 for the carbachol-induced effect was 375 +/- 8.7 nM (mean +/- SEM). The response was blocked by muscarinic antagonists in a dose dependent manner. However, the IC50 (94 +/- 3 nM) for the M3 antagonist 4-diphenyl acetoxy-N-methyl piperidine methobromide (4-DAMP) was considerably less than the other muscarinic antagonists (M1 antagonist pirenzepine, IC50 1340 +/- 110 nM; M2 antagonist AF-DX-116, IC50 6780 +/- 690 nM). These results suggest that the cholinergic input to the rat subthalamic nucleus exerts a postsynaptic excitatory action and this effect is likely mediated via muscarinic receptor type 3.

Animals↗

Metabolic activity of the basal ganglia in parkinsonian syndromes in human and non-human primates: a cytochrome oxidase histochemistry study.

In order to examine the consequences of nigrostriatal denervation on metabolic and functional activity of the basal ganglia, we analysed the distribution of cytochrome oxidase, a metabolic marker for neuronal functional activity, throughout the different basal ganglia structures in parkinsonian syndromes. The study was performed using enzyme histochemistry and densitometric measurements in patients with Parkinson's disease and in monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrydine (MPTP) intoxication. In MPTP-intoxicated monkeys compared to control animals, enzyme activity was significantly increased in the subthalamic nucleus and in the output nuclei of the basal ganglia, e.g. the internal segment of the globus pallidus and the substantia nigra pars reticulata, but remained unchanged in the external segment of the globus pallidus and the striatum. L-DOPA treatment reversed the increased enzyme activity in all of the affected structures studied. In contrast, in parkinsonian patients, who had all been chronically treated with L-DOPA, no changes in enzyme activity were detected compared to control subjects. The results in MPTP-intoxicated monkeys are in agreement with the accepted model of basal ganglia organization, in which the output nuclei of the basal ganglia are considered to be overactive after nigrostriatal denervation, partly due to increased activity of excitatory afferents from the subthalamic nucleus. Since the increased enzyme activity in MPTP-intoxicated monkeys was reversed by L-DOPA therapy, the unchanged cytochrome oxidase activity observed in parkinsonian patients might result from L-DOPA treatment, combined with the chronicity of nigrostriatal denervation.

Aged↗

Distribution of dopamine transporters in basal ganglia of cerebellar ataxic mice by [125I]RTI-121 quantitative autoradiography.

Dopamine (DA) uptake sites, or transporters, were examined with [125I]RTI-121 in mutant mice that exhibit motor control deficits, namely weaver, lurcher and dystonia musculorum. In lurcher mice, the distribution of [125I]RTI-121 binding was similar to controls, except for a decrease in the subthalamic nucleus. For dystonia musculorum mice, the labelling presented no differences between controls and mutants, except for decreases in the dorsal half of caudal neostriatum and in the ventral tegmental area. Moreover, in this mutant the left rostral neostriatum DA transporters were reduced, when compared to the right counterpart. In weaver heterozygote (wv/+) mice, the distribution and density gradients of [125I]RTI-121 labelling were similar as in their controls, except in caudal neostriatum, where binding was slightly higher. In contrast, the weaver homozygote (wv/wv) showed important decreases in labelling of the dorsal quadrant of rostral neostriatum as well as of the dorsal half of caudal neostriatum, where the reductions of binding densities were of 65% to 70%, respectively. There were also slight decreases in [125I]RTI-121 binding in olfactory tubercles as well as in subthalamic nucleus, but only in wv/wv mice. In substantia nigra pars compacta and ventral tegmental area of wv/wv mice the labelling was lower; however, while the 60% decrease in labelling in substantia nigra was highly significant, the 30% reduction in ventral tegmental area did not attain statistical significance. In summary, in the ataxic neurological mutant mice studied, important reductions of DA transporters were documented only for the weaver mice, the cerebellar mutant presenting, besides its cerebellar pathology, a known degeneration of mesencephalic dopaminergic neurons. The results rule out major alterations of the central DA systems in lurcher and dystonia musculorum, and are compatible with the hypothesis that the dopaminergic abnormalities of weaver mutants are not secondary to cerebellar atrophy, but may be a direct consequence of the abnormal weaver gene expressed by DA neurons leading to their apoptotic death.

Animals↗

Mechanisms of deep brain stimulation: an intracellular study in rat thalamus.

High-frequency deep brain stimulation (DBS) in the thalamus alleviates most kinds of tremor, yet its mechanism of action is unknown. Studies in subthalamic nucleus and other brain sites have emphasized non-synaptic factors. To explore the mechanism underlying thalamic DBS, we simulated DBS in vitro by applying high-frequency (125 Hz) electrical stimulation directly into the sensorimotor thalamus of adult rat brain slices. Intracellular recordings revealed two distinct types of membrane responses, both of which were initiated with a depolarization and rapid spike firing. However, type 1 responses repolarized quickly and returned to quiescent baseline during simulated DBS whereas type 2 responses maintained the level of membrane depolarization, with or without spike firing. Individual thalamic neurones exhibited either type 1 or type 2 response but not both. In all neurones tested, simulated DBS-evoked membrane depolarization was reversibly eliminated by tetrodotoxin, glutamate receptor antagonists, and the Ca(2+) channel antagonist Cd(2+). Simulated DBS also increased the excitability of thalamic cells in the presence of glutamate receptor blockade, although this non-synaptic effect induced no spontaneous firing such as that found in subthalamic nucleus neurones. Our data suggest that high-frequency stimulation when applied in the ventral thalamus can rapidly disrupt local synaptic function and neuronal firing thereby leading to a 'functional deafferentation' and/or 'functional inactivation'. These mechanisms, driven primarily by synaptic activation, help to explain the paradox that lesions, muscimol and DBS in thalamus all effectively stop tremor.

Animals↗

[Sleep in a case of hemiballism].

Sleep spindles abnormalities in extrapyramidal disorders have already been reported, but in the unilateral syndromes the data are unclear and inconclusive. In the attempt to clarify the problem we describe nocturnal sleep in a patient with hemiballism due to an ischemic damage of the subthalamic nucleus. The patient improved after one month haloperidol therapy and her unilateral (right) hyperkinesias disappeared. Electropolygraphic records (EEG, EOG, EMG of chin muscles, ECG) during spontaneous nocturnal sleep were obtained before therapy and after one month haloperidol treatment. The EEGs from bilateral fronto-central derivations were also recorded on magnetic tape to allow spectral analysis and automatic spindle detection by means of digital filtering. The pattern of spindle appearance rate for each stage 2 and 3 NonREM sleep in each night was investigated. We obtained: spindling index, that is the ratio between total spindle duration and sleep stage length, the mean number of spindle bursts/min, the average duration of sleep spindles, the mean amplitude, the mean time between spindles. Before therapy polygraphic records showed short total sleep time, a prolonged sleep latency, the lack of slow waves sleep and of REM sleep. After haloperidol treatment these parameters improved: total sleep time was longer, sleep latency shorter, slow waves sleep and REM sleep appeared. Before treatment spindle activity predominated in the left hemisphere - homolaterally to the subthalamic nucleus damage -, where the spindling index was higher, the mean number of spindle bursts/min larger, the mean time between spindles lower. After therapy, when hemisomatic hyperkinesias disappeared, spindle activity turned similar in the two hemispheres, since it decreased in the left hemisphere and it was unchanged in the right one.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

AMPA glutamate receptor activation in the posterior zona incerta inhibits amphetamine- and apomorphine-induced stereotypy.

Previous work demonstrated that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor antagonism in the zona incerta (ZI) dorsal to the subthalamic nucleus inhibits stereotypy in rats. The current investigation was undertaken to determine if AMPA receptors in a more caudal portion of the ZI have a role in the expression of stereotyped behavior. Rats were injected bilaterally with AMPA into the posterior ZI dorsal to the substantia nigra, and immediately given a systemic injection of d-amphetamine (10 mg/kg, s.c.) or apomorphine (1 mg/kg s.c.). AMPA produced a dose-dependent inhibition of stereotypy induced by both drugs which was prevented by the coadministration of the AMPA/kainic acid antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX) (0.5 microgram/0.5 microliter). A dose of AMPA as low as 62.5 ng completely abolished the oral component of stereotypy induced by both apomorphine and amphetamine. This dose of AMPA alone had no significant effect on spontaneous locomotor activity but enhanced the locomotor response stimulated by amphetamine (10 mg/kg, s.c.) due to an inhibition of stereotypy. The finding that activation of AMPA receptors in the posterior ZI inhibits stereotypy shows a contrast to results in the neighboring medial ZI dorsal to the subthalamic nucleus, where blockade of AMPA/kainic acid glutamate receptors with DNQX inhibits stereotypy.

Animals↗

Parkinson's Disease: Surgical Options.

Surgical therapy for Parkinson's disease (PD) has been a treatment option for over 100 years. Advances in the knowledge of basal ganglia physiology and in techniques of stereotactic neurosurgery and neuroimaging have allowed more accurate placement of lesions or "brain pacemakers" in the sensorimotor regions of target nuclei. This, in turn, has led to improved efficacy with fewer complications than in the past. Currently, bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) is the preferred option (and is approved by the US Food and Drug Administration) for the surgical treatment of PD. The most important predictors for outcome for DBS for PD are patient selection and electrode location. Patients should have a documented preoperative improvement from dopaminergic medication of at least 30% in the patient's Unified Parkinson's Disease Rating Scale motor disability scores. A levodopa challenge may be needed to document the best "on" state. Dementia or active cognitive decline must be excluded. Active psychiatric disease should be treated preoperatively. Patients should be motivated, with good support systems, and committed to the postoperative management of DBS therapy. Deep brain stimulation should be considered when the patient begins to experience dyskinesia and on-off fluctuations despite optimal medical therapy. Deep brain stimulation is not a good option at the final stages of the disease because of the increased incidence of dementia and severe comorbidity. The DBS electrode should be placed in the sensorimotor region of the GPi or STN. Subthalamic nucleus and GPi DBS can improve all motor aspects of PD, as well as predictable "on" time, without dyskinesia or fluctuations. On average, STN DBS results in a greater reduction of dopaminergic medication compared with GPi DBS. Because of the smaller size of the target region, the pulse generator battery life is longer with STN then with GPi DBS. Deep brain stimulation programming is a skill that is readily learned and may be required of all neurologists in the future. Emerging surgical therapies are restorative, and they aim to replace or regenerate degenerating dopaminergic neurons. These include embryonic mesencephalic tissue transplantation, human embryonic stem cell transplantation, and gene-derived methods of intracerebral implantation of growth factors and dopamine- producing cell lines. It will be important to determine whether DBS, if performed before the onset of motor response complications to medical therapy, may prevent this stage of disease altogether or delay it for a significant period of time. The same question applies to the future with restorative therapy.

Journal Article↗

A randomized trial of deep-brain stimulation for Parkinson's disease.

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

Activities of Daily Living↗

Long-term deep brain stimulation in elderly patients with cardiac pacemakers.

OBJECT: Deep brain stimulation (DBS) has become an accepted therapy for movement disorders such as Parkinson disease (PD) and essential tremor (ET), when these conditions are refractory to medical treatment. The presence of a cardiac pacemaker is still considered a contraindication for DBS in functional neurosurgery. The goal of this study was to evaluate the technical and clinical management of DBS for the treatment of movement disorders in elderly patients with cardiac pacemakers. METHODS: Six patients with cardiac pacemakers underwent clinical and cardiac examinations to analyze the safety of DBS in the treatment of movement disorders. Four patients suffered from advanced PD and two patients had ET. The mean age of these patients at surgery was 69.5 years (range 63-79 years). The settings of the pacemakers were programmed in a manner considered to minimize the chance of interference between the two systems. There were no adverse events during surgery. Four patients underwent stimulation of the thalamic ventralis intermedius nucleus (VIM), and two patients stimulation of the subthalamic nucleus. In general, bipolar sensing was chosen for the cardiac pacemakers. In all but one patient the quadripolar DBS electrodes were programmed for bipolar stimulation. Several control electrocardiography studies, including 24-hour monitoring, did not show any interference between the two systems. At the time this paper was written the patients had been followed up for a mean of 25.3 months (range 4-48 months). CONCLUSIONS: In certain conditions it is safe for patients with cardiac pacemakers to receive DBS for treatment of concomitant movement disorders. Cardiac pacemakers should not be viewed as a general contraindication for DBS in patients with movement disorders.

Aged↗

Effect of bilateral deep-brain stimulation on oral control of patients with parkinsonism.

We assessed the oral system of parkinsonian patients treated with bilateral chronic stimulation of the ventral intermediate nucleus of the thalamus (Vim), and of the subthalamic nucleus (STN) to compare the effects of these procedures on the articulatory organs. Force transducers were used to sample ramp-and-hold force contractions generated by the upper lip, lower lip and tongue at 1- and 2-newton target force levels, as well as maximal force. Fourteen healthy control subjects and 14 parkinsonian patients participated in this study. After an overnight fast the patients were evaluated under two conditions: during bilateral stimulation and 1 h after stopping stimulation. With Vim stimulation, dynamic and static control of the articulatory organs was worsened while with STN stimulation it was greatly improved. The target of stimulation differently influences the oral system and modulates neuronal structures involved in speech.

Adult↗

A horseradish peroxidase study of afferent connections of the globus pallidus in Macaca mulatta.

The high tonic discharge rates of globus pallidus neurons in awake monkeys suggest that these neurons may receive some potent excitatory input. Because most current electrophysiological evidence suggests that the major described pallidal afferent systems from the neostriatum are primarily inhibitory, we used retrograde transport of horseradish peroxidase (HRP) to identify possible additional sources of pallidal afferent fibers. The appropriate location was determined before HRP injection by mapping the characteristic high frequency discharge of single pallidal units in awake animals. In animals with injections confined to the internal pallidal segment, retrograde label was seen in neurons of the pedunculopontine nucleus, dorsal raphe nucleus, substantia nigra, caudate, putamen, subthalamic nucleus, parafascicular nucleus, zona incerta, medial and lateral subthalamic tegmentum, parabrachial nuclei, and locus coeruleus. An injection involving the external pallidal segment and the putamen as well resulted in additional labeling of cells in centromedian nucleus, pulvinar, and the ventromedial thalamus.

Afferent Pathways↗

Regional and cellular distribution of the P2Y(1) purinergic receptor in the human brain: striking neuronal localisation.

The biological actions of extracellular nucleotides are exerted via two families of P2 receptors, P2X and P2Y. The metabotropic P2Y receptors comprise at least 7 distinct subtypes, which have been cloned from a number of species. However, none of the P2Y receptor proteins have been visualised yet in human brain. In the present study, the regional and cellular distribution of the P2Y(1) receptor was investigated in the human brain by using immunohistochemistry. Polyclonal antibodies were raised against a synthetic peptide from the C-terminus of the P2Y(1) protein. Immunoblot analysis demonstrated that P2Y(1) antiserum specifically recognised a 63-kDa band in human and rat brain membranes. Similarly, the antiserum specifically detected the human P2Y(1) receptor in transfected 1321N1 cells. Immunohistochemical analysis on perfusion-fixed human brain tissue showed a widespread distribution for this receptor throughout the brain. At the cellular level, the P2Y(1) receptor was strikingly localised to neuronal structures of the cerebral cortex, cerebellar cortex, hippocampus, caudate nucleus, putamen, globus pallidus, subthalamic nucleus, red nucleus, and midbrain. Expression of the P2Y(1) receptor was not detected in other non-neuronal cell types. These results provide the first characterisation of the cellular distribution of a P2Y receptor in the human brain. The widespread and abundant distribution of the P2Y(1) receptor suggests its involvement in a number of important functions within the human brain. The neuronal localisation of this receptor points towards a possible role in neurotransmission, and also highlights a major role for extracellular nucleotides as signaling molecules within the brain.

Animals↗

Efferent connections of the centromedian and parafascicular thalamic nuclei: an autoradiographic investigation in the cat.

The efferent projections of the centromedian and parafascicular (CM-Pf) thalamic nuclear complex were analyzed by the autoradiographic method. Our findings show that the CM-Pf complex projects in a topographic manner to specific regions of the rostral cortex. These fibers distribute primarily to cortical layers I and III; however, the projection to layer I is more extensive. Following an injection into the rostral portion of the CM-Pf complex, label is found within the lateral rostral cortex, particularly within the presylvian, anterior ectosylvian, and anterior lateral sulci, and within the rostral medial cortex where label is present within the cruciate and anterior splenial sulci and anterior cingulate gyrus. An injection into the caudal dorsal portion of the CM-Pf complex results in label within the more ventral portions of the rostral lateral cortex where it is present within the anterior sylvian gyrus, presylvian regions, and gyrus proreus; and within the rostral medial cortex, where it is present within the rostral cingulate gyrus, and within the cruciate sulcus, and an extensive region ventral to the cruciate sulcus which includes the anterior limbic area. Injections into the caudal ventral portion of the CM-Pf complex result in virtually no cortical label, although a few labeled fibers are found in the subcortical white matter. The subcortical projection from the CM-Pf complex terminates within the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, zona incerta, fields of Forel, hypothalamus, thalamic reticular nucleus, and rostral intralaminar nuclei. Prominent silver grain aggregates are also present within the ventral lateral, ventral anterior, ventral medial, and lateral posterior nuclei, and ventrobasal complex. The aggregates in the thalamus appear to be fibers of passage, but whether these are also terminals cannot be determined with the techniques used in the present study.

Animals↗

Region-specific expression of the mRNAs encoding beta subunits (beta 1, beta 2, and beta 3) of GABAA receptor in the rat brain.

The expression of mRNAs encoding different beta subunits (beta 1, beta 2, and beta 3) of the gamma-aminobutyric acid A (GABAA) receptor in the rat brain was investigated by in situ hybridization histochemistry. Transcripts of each subunit showed region-specific localization. Some areas contained all three beta subunit mRNAs, while other areas showed marked differences in the location and level of expression of each subunit mRNA. The regions with strong to very strong labeling by the beta 3 probe were as follows: the olfactory bulb, the cortex, the caudate-putamen, the accumbens nucleus, the hypothalamus, the amygdala, the hippocampal formation, and some areas of the brainstem and spinal cord. Weak to moderate labeling was detected in the thalamus, superior and inferior colliculus, and many areas of the brainstem. The regions with strong to very strong labeling by the beta 2 probe were as follows: the olfactory bulb, the ventral pallidum, the globus pallidus, the nucleus of the diagonal band, the preoptic magnocellular nucleus, the thalamus, the subthalamic nucleus, the substantia nigra, and the cerebellum. Weak to moderate labeling was detected in the regions that showed strong expression of beta 3 subunit mRNA. Expression of beta 1 subunit mRNA was only weak to moderate compared to that of the beta 2 and beta 3 subunit mRNAs. The regions with moderate labeling by the beta 1 probe were the following: the cortex, the claustrum, the bed nucleus of the stria terminale, some nuclei of thalamus and amygdala, the hypothalamus, the hippocampal formation, the subiculum, the cerebellum, and several areas of the brainstem and spinal cord. Thus, our findings showed that the beta subunit mRNAs of the GABAA receptor were differentially expressed in the rat brain, perhaps indicating the existence of different subtypes of the GABAA receptor in different brain regions.

Animals↗

Differential expression of ErbB3 and ErbB4 neuregulin receptors in dopamine neurons and forebrain areas of the adult rat.

Neuregulins have been shown to play an important role in the development of the central nervous system, but their function in adult tissues is still unclear. We investigated the expression of the neuregulin receptors erbB3 and erbB4 in the adult rat brain by in situ hybridization histochemistry. Areas with considerable expression of erbB4 receptor mRNA include cortex, amygdala, hippocampus, medial habenula, reticular thalamic nucleus, several hypothalamic nuclei, subthalamic nucleus, substantia nigra pars compacta, and ventral tegmental area. Immunostaining for tyrosine hydroxylase and dopamine depletion by 6-hydroxydopamine indicate that erbB4 is expressed in dopamine neurons in the latter two nuclei. Substantial erbB4 expression is also present in clusters of cells along the ventral and medial border of the striatum/nucleus accumbens and in the subependymal zone along the lateral and olfactory ventricles (rostral migratory stream), suggesting a role for neuregulins in adult cell proliferation. In contrast, erbB3 mRNA is mostly expressed in white matter throughout the brain and in the ependyma of the ventral half of the third ventricle (tanycytes). These results demonstrate that expression of erbB3 and erbB4 receptors is widespread in the adult rat brain and suggest a function for neuregulins into adulthood.

Animals↗