Reflection of the Spatial Characteristics of an Acoustic Signal in the Activity of Caudate Nucleus Neurons

Studies were performed on five dogs. Chronic experimental conditions were used to study the responses of individual neurons in the caudate nucleus to the spatial characteristics of an acoustic signal. The results showed that 92% of sound stimulus-responsive neurons in the head of the caudate nucleus in dogs generated asymmetrical responses to contra- and ipsilateral monaural stimulation, with contralateral stimulation being more effective. In 50% of caudate nucleus neurons, simultaneous stimulation of both sound inputs was more effective than contralateral stimulation. A total of 77% of sound-responsive caudate neurons demonstrated sensitivity to changes in the magnitude and sign of the interaural delay.     

Intracellular targeting and protein kinase C in vascular smooth muscle cells: specific effects of different membrane-bound receptors

Protein kinase C is an important second messenger system, which is translocated from the cytosol to the cell membrane upon cell stimulation. We used confocal microscopy to study the spatial distribution of protein kinase C isoforms after stimulation of cultured vascular smooth muscle cells with different agonists. First, we analysed the effects of angiotensin II and platelet-derived growth factor (PDGF). Confocal microscopy showed a rapid assembly of PKC α along cytosolic fibres followed by a translocation towards the nucleus with angiotensin II. PDGF engendered a similar, but much slower response; however, a cytoskeletal distribution was not observed. We then investigated the effects of thrombin and bFGF on nuclear translocation. bFGF induced a rapid translocation of the isoform towards the perinuclear region and into the nucleus. bFGF had a similar effect on PKC ?. In contrast, thrombin had a smaller effect on nuclear translocation of PKC α and did not influence PKC ?, but instead induced a rapid nuclear translocation of PKC ζ. Thus, tyrosine kinase receptor activation via bFGF induces a rapid association of PKC α and ? within nuclear structures. Our results show that agonists cause, not only a translocation of protein kinase C isoforms into the cell membrane but also into the cell nucleus. Lastly, we analyzed the nuclear immunoreactivity of the PKC isoforms α, δ,? and ζ in vascular smooth muscle cells during the cell cycle. Resting cells were stimulated with foetal calf serum (FCS, 10%), which translocated PKC α and ? to the perinuclear region and into the nucleus, while PKC δ and ζ showed no increase in nuclear immunoreactivity. After 4 h of FCS, the nuclear immunoreactivity for PKC α and ? was reduced to or below control values. At 8 h, increased nuclear expression of isoforms α,? and ζ was observed, while isoform δ was not affected. Our results demonstrate a complex spatial and temporal regulation of PKC isoforms in response to vasoactive hormones and growth factors. We suggest that protein kinase C may be important for nuclear signaling and demonstrate that nuclear translocation of PKC isoforms is differentially regulated during the cell cycle.     

Effects of neonatal cortical lesions upon retinocollicular projections in the hamster

Autoradiography and anterograde horseradish peroxidase transport were used to examine retinocollicular projections in normal hamsters and in animals subjected to ablation of the ipsilateral, posterior neocortex at 1, 3, 6, 10 or 120 days of age. The crossed retinotectal projections of all groups were quite similar. There did, however, appear to be a slight increase in the density of the projection to the lower portion of the stratum griseum superficiale in the neonatally brain-damaged hamsters.The uncrossed pathway, on the other hand, was quite abnormal in the neonatally lesioned animals. In normals, the ipsilateral retinocollicular projection consisted almost entirely of a series of patches along the stratum yriseum superficiale-stratum opticum border in the rostral one-third of the colliculus. Only a few axons from the ipsilateral eye were observed in the caudal two-thirds of the tectum and these could only be visualized when horseradish peroxidase was used as the tracer. In all of the neonatally brain-damaged hamsters both autoradiography and horseradish peroxidase tracing demonstrated that the ipsilateral retina densely innervated the entire rostrocaudal extent of the colliculus.Retrograde tracing experiments demonstrated that the portion of the temporal retina which gave rise to the uncrossed retinocollicular projection in the normal hamsters was also the source of the expanded projection in the neonatally brain-damaged animals; and, further, that the numbers and areal distributions of ipsilaterally projecting retinal and retinocollicular ganglion cells were similar in the two groups.These findings suggest that, at least in the hamster, normal inputs from the two eyes may not be a sufficient condition for the development of the largely complementary pattern of collicular innervation by the two retinae.     

Migratory pathways and selective aggregation of the lateral reticular neurons in the rat embryo: a horseradish peroxidase in vitro study, with special reference to migration patterns of the precerebellar nuclei

The migration and ultimate domain invasion of postmitotic lateral reticular nucleus (LRN) neurons were followed in embryonic day 15-20 (E15-E20) rat embryos, by using a horseradish peroxidase (HRP) in vitro axonal tracing method. All of the LRN axons elongate and neuronal somata migrate via the subpial or marginal migratory stream (mms), circumnavigating the ventrolateral aspect of the medulla at the glial endfeet level. They reach the ventral midline at E16, bypass it, and begin to settle in their final territory at E17. At E18 the LRN anlage is fully formed, and at E19-E20 its cells have finished their migration and are rapidly differentiating. Comparison of these sequential steps with their counterparts in the development of the inferior olive (ION) and external cuneatus (ECN) brings to light the essential role of the neuroepithelial cells of the interolivary commissure (the "floor plate"). This zone is likely to act as 1) a chemoattractant for the growth cones of the LRN, ION, and ECN, and 2) a decision-making center, which instructs the somata of these neurons to cross the midline or not, ultimately governing the crossed or uncrossed pattern of their projection to their common target, the cerebellum. Finally, the ontogeny of the LRN and ECN provides a most surprising example, even unique in the central nervous system, of long-distance, neurophilic migration that conveys neuronal cell bodies contralaterally to the side on which they proliferate.     

Evidence for feeding elicited through antihistaminergic effects of tricyclic antidepressants in the rat hypothalamus

We studied central mechanisms of antidepressants that affect feeding behavior in rats. The tricyclic compounds amitriptyline, doxepin and imipramine significantly induced feeding after their infusion into the third cerebral ventricle in the light phase, but the tricyclic, desipramine, and the dicyclic zimelidine, did not. Drinking was not affected by any compound tested. The relative order of potency in eliciting feeding was: amitriptyline and doxepin > imipramine > desipramine and zimelidine. To clarify the involvement of neuronal histamine in antidepressant-induced feeding, alpha-fluoromethylhistidine (FMH), a suicide inhibitor of histidine decarboxylase, was intraperitoneally administered before infusion of amitriptyline. FMH attenuated the amitriptyline's effect. Bilateral microinfusion of amitriptyline into the ventromedial hypothalamus or the paraventricular nucleus verified that these are loci for the modulation of feeding by amitriptyline. In the lateral hypothalamus, amitriptyline was less effective. These findings indicate that tricyclic antidepressants directly facilitate feeding, which is, at least in part, mediated by histamine in the hypothalamus.     

Presynaptic opioid receptors on dopaminergic nerves in the rabbit caudate nucleus: coupling to pertussis toxin-sensitive G-proteins and interaction with D2 autoreceptors?

Slices of the rabbit caudate nucleus, preincubated with [³H]dopamine and subjected to electrical field stimulation, were used (1) to investigate the involvement of G-proteins in the signal transduction of presynaptic D₂ (auto)receptors and -opioid receptors on dopaminergic axon terminals in this tissue and (2) to study a possible mutual interaction of these two presynaptic receptors. Pretreatment of the slices with either pertussis toxin (8 g/ml; 18 h), or N-ethylmaleimide (30 M, 30 min) significantly reduced the inhibitory effects of both the D₂ agonist quinpirole and the -opioid receptor agonist U-50488H on the [³H]overflow evoked by 36 pulses (2 ms, 24 mA, 0.3 Hz), suggesting the coupling of both receptors to G-proteins.Experiments designed to study possible interactions of these two presynaptic receptors were carried out under stimulation conditions (only 1 pulse), which strongly diminish interference of endogenous transmitters released in the tissue with modulatory effects of exogenous drugs. For instance, due to the presence of endogenous dopamine, quinpirole was much less potent during 36-pulse-than during 1-pulse field stimulation, whereas the D₂ antagonist domperidone was almost without effect in the latter case. Using the 1-pulse stimulation paradigm, the concentration/response curve of quinpirole was unaffected in the presence of the halfmaximal inhibitory concentration of U-50,488 H (0.1 M). On the other hand, also quinpirole at its halfmaximal inhibitory concentration (0.1 M), hardly affected the concentration/response curve of U-50,488 H: only high concentrations of U-50,488 H (above 1 M) seemed to be slightly less effective in the presence than in the absence of the D₂ agonist. U-50,488 H, at these high concentrations, was also less potent under 36-pulse than under 1-pulse stimulation conditions. From these findings, we conclude that there is only a limited interaction between presynaptic D₂ autoreceptors and -opioid receptors on dopaminergic axon terminals in the rabbit caudate nucleus, despite they are both coupled to PTX/NEM-sensitive G-proteins. Correspondence to: R. Jackisch at the above address     

Excitotoxic lesions of the pedunculopontine tegmental nucleus disinhibit orofacial behaviours stimulated by microinjections of d-amphetamine into rat ventrolateral caudate-putamen

Data are presented which support the hypothesis that the pedunculopontine tegmental nucleus serves as an output station for the striatum and, in particular, has a role in the expression of behaviour stimulated from the ventrolateral caudate-putamen, a rodent homologue of the primate putamen. Rats received either bilateral ibotenate or sham lesions in the pedunculopontine tegmental nucleus and bilateral cannulation of the ventrolateral caudate-putamen. Oral motor activities were observed following microinjection of 5.0, 10.0 and 20.0 g d-amphetamine (and vehicle-only control) into the ventrolateral caudate-putamen. As expected, orofacial behaviours such as biting and licking were observed in sham-lesioned rats following this treatment, but pedunculopontine tegmental nucleus-lesioned rats exhibited an increase in the incidence of these oral motor behaviours at all doses of amphetamine compared with the controls. This increase was the product of changes in the duration and number of times in which they engaged in oral motor behaviours, but not the latency to initiate them. There was no change in the normal oral motor activities associated with grooming. Histological analysis showed that ibotenate lesions destroyed both cholinergic and non-cholinergic neurones in the pedunculopontine tegmental nucleus. These data indicate that loss of the pedunculopontine tegmental nucleus disinhibits oral motor behaviours stimulated from the ventrolateral caudateputamen by d-amphetamine and are discussed in terms of their implications for understanding the relationships between striatal outflow and structures in the pons.     

Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats

Paired clicks were presented to awake, freely-moving rats to examine neuronal activity associated with inhibitory gating of responses to repeated auditory stimuli. The rats had bundles of eight microwires implanted into each of four different brain areas: CA3 region of the hippocampus, medial septal nucleus, brainstem reticular nucleus, and the auditory cortex. Single-unit recordings from each wire were made while the local auditory-evoked potential was also recorded. The response to a conditioning stimulus was compared to the response to a test stimulus delivered 500 ms later: the ratio of the test response to the conditioning response provided a measure of inhibitory gating. Auditory-evoked potentials were recorded at all sites. Overall, brainstem reticular nucleus neurons showed the greatest gating of local auditory-evoked potentials, while the auditory cortex showed the least. However, except for the auditory cortex, both gating and non-gating of the evoked response were recorded at various times in all brain regions. Gating of the hippocampal response was significantly correlated with gating in the medial septal nucleus and brainstem reticular nucleus, but not the auditory cortex. Single-unit neuron firing in response to the clicks was most pronounced in the brainstem reticular nucleus and the medial septal nucleus, while relatively few neurons responded in the CA3 region of the hippocampus and the auditory cortex. Taken together, these data support the hypothesis that inhibitory gating of the auditory-evoked response originates in the non-lemniscal pathway and not in cortical areas of the rat brain.     

Unilateral dopamine depletion paradoxically enhances amphetamine-induced Fos expression in basal ganglia output structures

The ability of amphetamine to induce expression of the immediate early gene protein, Fos, was examined by immunocytochemistry in animals with unilateral 6-hydroxydopamine lesions of the nigrostriatal bundle. Amphetamine induced Fos expression in the globus pallidus (GP) on the intact side of the brain, but this response was greatly attenuated on the dopamine-depleted side. In contrast, amphetamine induced little Fos expression in the entopeduncular nucleus (EPN) and the substantia nigra pars reticulata (SNpr) on the intact side of the brain, but resulted in pronounced expression in these structures on the lesioned side. These findings demonstrate that unilateral dopamine depletion results in a pathophysiological state in which some responses to amphetamine are attenuated while others are paradoxically potentiated. One explanation of these effects is that amphetamine may indirectly activate excitatory inputs to the SNpr and the EPN on both sides of the brain. On the intact side, these effects would be opposed by the simultaneous activation of inhibitory pathways arising in the striatum and the GP, with the result that little Fos expression would be seen. On the dopamine-depleted side, however, engagement of these inhibitory pathways would be attenuated and the unopposed effects of the excitatory inputs mobilized by amphetamine would result in exaggerated Fos synthesis.