Experimental Brain Research

Sato, Akio; Sato, Yuko; Schmidt, Robert

doi: 10.1007/BF00242176pmid: 7589306

221 105 105 1 1 Akio Sato 81-3-3964-3241 81-3-3964-1415 Yuko Sato Robert F. Schmidt Department of the Autonomic Nervous System Tokyo Metropolitan Institute of Gerontology 35-2 Sakaecho, Itabashi-ku 173 Tokyo Japan Laboratory of Physiology, Tsukuba College of Technology 305 Tsukuba Japan Physiologisches Institut der Universität Würzburg Röntgenring 9 D-97070 Würzburg Germany Abstract Modulation of somatosympathetic reflexes at the spinal cord and the brainstem was studied by administering opioid receptor agonists into the intrathecal space of the lumbar spinal cord and into the subarachnoid space of the cisterna magna in rats anesthetized with α-chloralose and urethane. Somatocardiac sympathetic A-and C-reflexes were elicited by electrical stimulation of myelinated (A) and unmyelinated (C) afferent fibers of the tibial nerve, respectively. Intrathecal administration of the μ-opioid receptor agonist DAMGO selectively depressed the C-reflex in a dose-dependent manner (minimum effective dose 10 ng), whereas the intrathecal injection of the δ-opioid receptor agonist DPDPE and the κ-opioid receptor agonist U-50,488H only at doses of 10 μg and 100 μg, respectively, led to a significant depression of the C-reflex. Injection of DAMGO into the cisterna magna enhanced both A-and C-reflexes in a dose-dependent manner (minimum effective dose 1 ng). The administration of neither DPDPE nor U-50,488H into the cisterna magna affected A-or C-reflexes. It is concluded that the activation of μ-opioid receptors is mainly or exclusively responsible for suppressing somatosympathetic C-reflexes at the spinal cord and for enhancing them at the brainstem.

Lu, S.; Guido, W.; Vaughan, J.; Sherman, S.

doi: 10.1007/BF00242177pmid: 7589320

221 105 105 1 1 S. -M. Lu W. Guido J. W. Vaughan S. M. Sherman 1-516-632-8620 1-516-632-6661 [email protected] Institute for Developmental Neuroscience Peabody College, Vanderbilt University Box 152 37203 Nashville TN USA Department of Anatomy LSU Medical Center 1901 Perdido St. 70112-1393 New Orleans LA USA Department of Neurobiology State University of New York 11794-5230 Stony Brook NY USA Abstract We constructed average histograms from responses evoked by flashing stimuli and noted previously described variations in the shape of the response profile, particularly with respect to sharpness of the peak. To express this variable, we measured the half-rise latency, which is the latency from stimulus onset required to reach half the maximum response. A short half-rise latency, which is characteristic of nonlagged cells, is associated with a brisk response and sharp peak; a long half-rise latency, characteristic of lagged cells, is associated with a sluggish response and broad peak. Nonlagged cells were readily seen; we attempted to identify cells with long latencies as lagged, but we were unable to do so unambiguously due to failure to observe lagged properties other than latency. We thus refer to these latter cells as having “lagged-like” responses to indicate that we are not certain whether these are indeed lagged cells. In addition to the histograms, we analyzed the individual response trials that were summed to create each histogram, and we used spike density analysis to estimate the initial response latency to the flashing spot for each trial. We found that lagged-like responses were associated with more variability in initial response latency than were nonlagged responses. We then employed an alignment procedure to eliminate latency variation from individual trials; that is, responses during individual trials were shifted in time as needed so that each had a latency equal to the average latency of all trials. We used these “aligned” trials to create a second, “aligned” response histogram for each cell. The alignment procedure had little effect on nonlagged responses, because these were already well aligned due to consistent response latencies amongst trials. For lagged-like responses, however, the alignment made a dramatic difference. The aligned histograms looked very much like those for nonlagged responses: the responses appeared brisk, with a sharply rising peak that was fairly high in amplitude. We thus conclude that the slow build up to a relatively low peak of firing of the lagged-like response histogram is not an accurate reflection of responses on single trials. Instead, the sluggishness of lagged-like responses inferred from average response histograms results from temporal smearing due to latency variability amongst trials. We thus conclude that there is relatively little difference in briskness between nonlagged and lagged-like responses to single stimuli.

Wang, J.; Dutia, M.

doi: 10.1007/BF00242178pmid: 7589314

221 105 105 1 1 J. -J. Wang M. B. Dutia 44-131-650 6527 Department of Biology Nanjing University Nanjing China Department of Physiology Medical School Teviot Place EH8 9AG Edinburgh UK Abstract The tonic discharge of 71 medial vestibular nucleus (MVN) neurones was recorded in slices of the dorsal brainstem of young adult rats. Bath application of histamine caused a dose-related excitation in 59 of the 71 cells (83%), the remaining 12 (17%) being unresponsive. Dimaprit, a selective H 2 agonist, also caused excitation in all 20 cells tested. The histamine-induced excitation and the response to dimaprit were antagonised by the selective H 2 antagonist ranitidine, confirming that the H 2 subtype of histamine receptor is involved in mediating the effects of histamine on these cells. Triprolidine, a selective H 1 antagonist, also antagonised the excitation caused by histamine, at a concentration (0.3 μM) which left the H 2 receptor-mediated response to dimaprit unchanged. Thus the excitatory effects of histamine on MVN cells in the rat involve two components mediated through H 1 and H 2 receptor-linked mechanisms, respectively. Betahistine, a weak H 1 agonist and H 3 antagonist, had little excitatory action when applied on its own, but significantly reduced the excitation caused by histamine when the two drugs were applied together. The effects of betahistine were consistent with a partial-agonist action at H 1 receptors on MVN cells, reducing the excitatory responses to histamine presumably by occupying these receptor sites in competition with the exogenously applied neurotransmitter. This partial-agonist action of betahistine may be an important part of its mechanism of action in the symptomatic treatment of vertigo and motion sickness, since it is likely to occur not only in the MVN but also in many brain regions, including the thalamus and cortex, which express H 1 receptors and which are innervated by the hypothalamic histaminergic system. Thus the effectiveness of betahistine and other anti-H 1 drugs against motion sickness may be explained by their action in reducing the effects of the excess histamine release induced in such conditions in various brain areas, including the MVN.

Noga, B.; Jankowska, E.; Skoog, B.

doi: 10.1007/BF00242179pmid: 7589315

221 105 105 1 1 B. R. Noga 1-204-789-3762 1-204-786-0932 [email protected] E. Jankowska B. Skoog Department of Physiology University of Manitoba R3E 0W3 Winnipeg Manitoba Canada Department of Physiology University of Göteborg Medicinaregatan 11 41390 Göteborg Sweden Abstract The effects of short trains of electrical stimuli applied within the cuneiform nucleus and the subcuneiform region were examined on transmission from group I and group II muscle afferents to first-order spinal neurons. Variations in the effectiveness of transmission from these afferents were assessed from changes in the sizes of the monosynaptic component of extracellular field potentials evoked following stimulation of muscle nerves. Field potentials evoked from group II muscle afferents in the dorsal horn of the midlumbar and sacral segments and in the intermediate zone of the midlumbar segments were reduced when the test stimuli applied to peripheral nerves were preceded by conditioning stimulation of the cuneiform nucleus or the subcuneiform region. The depression occurred at conditioning-testing intervals of 20–400 ms, being maximal at intervals of 32–72 ms for dorsal horn potentials and 40–100 ms for intermediate zone potentials. At the shortest intervals, both group II and group I field potentials in the intermediate zone were depressed. Conditioning stimulation of the cuneiform nucleus depressed group II field potentials nearly as effectively as conditioning stimulation of the coerulear or raphe nuclei. We propose that the nonselective depression of transmission from group I and II afferents at short intervals is due to the activation of reticulospinal pathways by cells or fibers stimulated within the cuneiform area. We also propose that the selective depression of transmission from group II afferents at long intervals is mediated at least partly by monoaminergic pathways, in view of the similarity of the effects of conditioning stimulation of the cuneiform nucleus and of the brainstem monoaminergic nuclei and by directly applied monoamines (Bras et al. 1990). In addition, it might be caused by primary afferent depolarization mediated by non-monoaminergic fibers (Riddell et al. 1992).

Skoog, B.; Noga, B.

doi: 10.1007/BF00242180pmid: 7589316

221 105 105 1 1 B. Skoog B. R. Noga Department of Physiology and Pharmacology Göteborg University Medicinaregatan 11 41390 Göteborg Sweden Department of Physiology University of Manitoba R3EOW3 Winnipeg Manitoba Canada Abstract The effects of dopamine and its agonists on transmission from muscle afferents to spinal neurones were investigated in the cat and guinea-pig spinal cord, by measuring the drug effects on the amplitude of monosynaptic field potentials evoked by electrical stimulation of group I and group II muscle afferents. Local iontophoretic application of dopamine, the dopamine D1/D5 agonist SKF-38393 and the D2/D3/D4 agonist quinpirole all depressed the group II field potentials evoked at the base of the dorsal horn. Group II field potentials in the intermediate zone were depressed by dopamine to a similar degree as the dorsal horn field potentials, whereas the dopamine agonists were without effect upon them. The intermediate zone field potentials evoked by group I muscle afferents were not depressed by any of the drugs. The dopamine-evoked depression of the group II-evoked field potentials in the dorsal horn in the guinea-pig spinal cord was reduced by the simultaneous application of haloperidol. The results demonstrate that dopamine receptors mediate the depression of transmission from group II muscle afferents to interneurones in the dorsal horn, but not to neurones in the intermediate zone of the spinal cord.

Burbaud, P.; Gross, C.; Benazzouz, A.; Coussemacq, M.; Bioulac, B.

doi: 10.1007/BF00242181pmid: 7589317

221 105 105 1 1 P. Burbaud C. Gross A. Benazzouz M. Coussemacq B. Bioulac Laboratoire de Neurophysiologie URA CNRS 1200, Université de Bordeaux II 146 rue Léo Saignat F-33076 Bordeaux France Laboratoire d'Immunologie et Neuropathologie, Université de Bordeaux II 146 rue Léo Saignat F-33076 Bordeaux France Abstract The effect of subthalamic nucleus (STh) lesion on apomorphine-induced rotational behaviour and unit activity of substantia nigra pars reticulata (SNr) neurons was studied in normal, sham-control and unilateral 6-OHDA-lesioned rats (SN pars compacta (SNc)-lesioned). In the latter, contraversive rotational behaviour was greatly reduced by an additional ipsilateral STh lesion. A moderate ipsiversive rotation was observed in rats with a single STh lesion. Concurrently, SN unit extracellular recordings were performed in age-matched normal rats, sham-controls for both lesions, STh-lesioned rats, SNc-lesioned rats, and SNc-lesioned rats with an ipsilateral STh lesion (SNc+STh-lesioned). Pars reticulata neurons had a higher mean firing rate in SNc-lesioned rats than in control rats. Furthermore, 68% of SNr neurons in SNc-lesioned rats had a tonic discharge pattern (against 92.3% in control rats) and 32% a mixed or bursting pattern. After STh lesion, a clear decrease in SNr firing rate was observed in SNc-lesioned rats. Moreover, STh lesion improved interspike interval regularity and decreased the occurrence of bursting patterns. In rats with a single STh lesion, the firing rate was no different from that of the sham-controls but the discharge pattern was more regular. These data show that STh lesion decreased apomorphine-induced rotational behaviour in dopamine-depleted animals. This effect could be related to the suppression of the exitatory effect of STh efferents on the SNr neurons. STh lesion both counterbalanced the increased activity of SNr neurons and regularized their discharge pattern.

Seiler, Magdalene; Aramant, Robert

doi: 10.1007/BF00242182pmid: 7589318

221 105 105 1 1 Magdalene J. Seiler 1-502-852-7442 1-502-852-0128 Robert B. Aramant Department of Ophthalmology and Visual Sciences and Department of Anatomical Sciences and Neurobiology University of Louisville Medical School 40292 Louisville KY USA Abstract After transplantation of embryonic retinal cells to injured adult retina, it is often difficult to distinguish donor from host cells. To overcome this problem, two methods were applied: labelling donor cells with the nuclear marker bromodeoxyuridine (BrdU) and use of transgenic donor tissue. BrdU was injected into timedpregnant rats on 2 or 3 consecutive days. The donor embryos were taken 1–4 days later for transplantation. The BrdU-labelled donor tissue was examined in transplants sampled up to 1 year after grafting. Labelled donor cells were specifically identified in the transplants and in the interface with the adjacent host retina. The varying intensities of cell labelling indicated differences in the initial uptake of BrdU in the S-phase, or the dilution of the label by cell divisions after BrdU injection. The best labelled cells were presumably the ones that stopped dividing shortly after injection of BrdU. As controls, the normal development of BrdU-labelled retinas from the offspring of females that had been BrdU-injected at E16 and E17 and not used for transplantation was studied. Near the time of birth, clones of labelled cells were radially distributed. In the mature retina, labelled cells were seen in all retinal layers. Embryonic retina derived from transgenic (NSE-lacZ) mice was transplanted to ‘nude’, immunodeficient rats (xenografts). These transgenic mice contain the Escherichia coli β-galactosidase gene, coupled to the promoter for neuron-specific enolase (NSE). Thus, all retinal donor cells that contain NSE could be identified by histochemistry or immunohistochemistry. The donor cells expressing the transgene could be detected several months after transplantation.

Gynther, B.; Vickery, R.; Rowe, M.

doi: 10.1007/BF00242183pmid: 7589319

221 105 105 1 1 B. D. Gynther R. M. Vickery M. J. Rowe 61-2-385-1059 School of Physiology and Pharmacology, University of New South Wales 2052 Sydney NSW Australia Abstract Transmission from single, identified, slowly adapting type II (SAII) tactile fibers to their target neurons in the cuneate nucleus was examined in anesthetized cats. Simultaneous recordings were made from cuneate neurons and from fine, intact fascicles of the superficial radial nerve in which it was possible to identify and monitor the activity of each group II fiber. Selective activation of individual SAII fibers was achieved by means of skin stimulation with fine probes, in conjunction with extensive forelimb denervation. Responses were studied for seven SAII-driven cuneate neurons. For three there was unequivocal monitoring of the identified SAII input fiber. However, in six of the seven there was evidence that just one SAII fiber provided suprathreshold input to the cuneate neuron, and neither temporal nor spatial summation was required for reliable transmission. Cuneate impulse rates, in response to SAII inputs lasting 1 s, were less than 250 impulses per second, even though the SAII impulse rates could be 500 s -1 . Responses to individual SAII impulses consisted of a burst of 2–3 impulses at low SAII input rates, but burst responses disappeared at high SAII rates. In all three SAII-cuneate pairs studied, the transmission security (the percentage of SAII impulses that evoked cuneate spike output) exceeded 80% in response to static skin displacement and in response to certain frequencies of skin vibration, in particular, at 100–200 Hz, exceeded 98% when the SAII fiber responded near the 1∶1 level (one impulse per vibration cycle). Transmission characteristics for the SAII-cuneate linkage resulted in the cuneate neuron showing tight phaselocking of responses to high-frequency (>100 Hz) vibrotactile stimuli and higher impulse rates than its SAII input (up to input rates of ∼50 impulses s -1 ). Security of transmission across the SAII-cuneate synapse is similar to that demonstrated previously for tactile fibers of the SAI and Pacinian corpuscle (PC)-related classes, which suggests that there is no marked differential specialization in transmission characteristics for dorsal column nuclei neurons that receive input from different tactile fiber classes. Furthermore, it means that the reported failure of individual SAII fiber inputs to generate conscious sensation in man following intraneural microstimulation is not related to transmission failure at the first central relay.

Reading, Paul; Dunnett, Stephen

doi: 10.1007/BF00242184pmid: 7589321

221 105 105 1 1 Paul J. Reading Stephen B. Dunnett 44-1223-331174 MRC Cambridge Centre for Brain Repair, University of Cambridge Forvie Site, Robinsonway CB22PY Cambridge UK Abstract Bilateral damage to the ventral striatum induced by the excitotoxin ibotenic acid was found to have profound disinhibitory effects on rats' behaviour. Lesioned animals were unable to acquire efficient levels of performance on an operant schedule (differential reinforcement of low rates of responding, DRL) that required them to inhibit a previously rewarded response. In addition, lesioned subjects were relatively resistant to the disruptive effects of amphetamine on performance of the DRL schedule and were slower to cease responding under conditions of non-reward. A measure of unconditioned behaviour, overnight locomotor activity, was also disinhibited by the presence of the lesion. Grafts of embryonic striatal tissue transplanted to the lesioned ventral striatum were found to survive well. Moreover, the presence of the grafts reversed the effects of the lesion on measures of conditioned and unconditioned behaviour. The nature of the lesion-induced behavioural deficit and the ability of the embryonic transplants to reverse it are discussed in terms of the possible restoration of limbicsubcortical circuitry.

Li, Xing; Phillips, Russell; LeDoux, Joseph

doi: 10.1007/BF00242185pmid: 7589322

221 105 105 1 1 Xing Fang Li Russell Phillips Joseph E. LeDoux [email protected] Center for Neural Science, New York University 6 Washington Place 10003 New York NY USA Department of Psychology New York University 10003 New York NY USA Abstract We examined whether the NMDA class of excitatory amino acid receptors contribute to synaptic transmission in the pathway connecting the medial geniculate body (MGB) with the lateral nucleus of the amygdala (LA) using extracellular single unit recordings and microiontophoresis. Cells were identified in LA on the basis of responsivity to electrical stimulation of the MGB. For each cell, a level of current was found for the iontophoretic ejection of the NMDA antagonist AP5 that blocked responses elicited by iontophoresis of NMDA, but had no effect on responses elicited by AMPA. Iontophoresis of AP5 with this level of current blocked the excitatory response elicited by MGB stimulation in most cells tested. Microinfusion of AP5 (25, 50, or 100 μM) also blocked the responses. Additional studies tested individual cells with both AP5 and the AMPA antagonist CNQX and showed that blockade of either NMDA or AMPA receptors interferes with synaptic transmission. Finally, iontophoretic ejection of either AP5 or CNQX blocked short-latency (<25 ms) responses elicited in LA by peripheral auditory stimulation. Together, these results suggest that the synaptic evocation of action potentials in the thalamo-amygdala pathway depends on both NMDA and non-NMDA receptors. We hypothesize that non-NMDA receptors are most likely required to depolarize the cell sufficiently to remove the blockade of NMDA channels by magnesium and NMDA receptors are required to further depolarize the membrane to the level required for action potential generation.