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R H Baisden

Publications and source records attributed to R H Baisden.

At least 19 recordsLinked to original sources

Axotomy-induced loss of m2 muscarinic receptor mRNA in the rat facial motor nucleus precedes a decrease in concentration of muscarinic receptors.

The abundance of muscarinic receptors and m2 muscarinic receptor mRNA in the facial nuclei of rats was evaluated by autoradiographic procedures at various times up to 14 days after transection of the right facial nerve. Receptors were labelled by in vitro incubation of brain sections with L-[3H]quinuclidinyl benzilate, while in situ hybridization with a 35S-labelled oligonucleotide was used to identify m2 muscarinic receptor mRNA in neighbouring sections. The right and left facial nuclei of non-operated control rats appeared equivalent in abundance of muscarinic receptors (359 +/- 8 versus 376 +/- 9 fmol per mg tissue, n = 5) and the presence of m2 mRNA. Axotomy had no effect on the concentration of receptors in the contralateral facial nucleus but caused a gradual loss of receptors from the ipsilateral side. No change was detected at 1 day after nerve transection, but a 23% decrease relative to the contralateral facial nucleus had occurred by 3 days. A maximum decrease of 51% was achieved by 1 week after nerve transection. By comparison, m2 mRNA was nearly eliminated from the ipsilateral facial nucleus at 1 day post-taxonomy and remained depleted for the duration of study. Previous work has established that no significant loss of motoneurons occurs within this period. Accordingly, it is postulated that axonal injury inhibits transcription of the m2 muscarinic receptor gene, resulting in a later decrease in muscarinic receptor protein expression.

Animals↗

Effects of trimethyltin (TMT) on choline acetyltransferase activity in the rat hippocampus. Influence of dose and time following exposure.

Trimethyltin (TMT) destroys specific subfields of the hippocampus in the rat. TMT also increases choline acetyltransferase (ChAT) activity in CA1 of Ammon's horn and the outer molecular layer of the dentate gyrus. This observation suggests that axonal sprouting occurs in the cholinergic septohippocampal system in response to TMT. However, neither does-response nor time course data are available for the effects of TMT on this enzyme. The effects of three dose levels of TMT on ChAT activity in CA1 and the dentate gyrus were determined in Experiment 1 and ChAT activity in these two areas was measured at six time points following exposure to TMT in Experiment 2. Only the highest dose of TMT (6 mg/kg) significantly increased ChAT activity. ChAT activity in the dentate gyrus increased significantly by 3 d after administration and continued to increase until 21 d after exposure. A significant increase was not observed in CA1 until 7 d after exposure to TMT. Asymptotic levels were still reached at d 21. These results indicate a steep dose-response curve for TMT-induced changes in ChAT activity in the hippocampal formation and that this marker of cholinergic activity is more sensitive to perturbation by TMT in the dentate gyrus than Ammon's horn.

Animals↗

The effect of time following exposure to trimethyltin (TMT) on cholinergic muscarinic receptor binding in rat hippocampus.

Adult male Long-Evans rats were given 6 mg/kg trimethyltin (TMT). Rats were killed 1, 3, 7, 14, 21, 35, or 60 d later. An untreated control group was included. Brain sections were processed using film autoradiography to visualize in the hippocampus either total muscarinic receptor binding ([3H]quinuclidinyl benzilate; [3H]QNB), or M1 receptors ([3H]pirenzepine; [3H]PZ), or M2 receptors ([3H]oxotremorine-M; [3H]OXO-M). A reduction in [3H]QNB binding was found in CA1 and CA3c 7 d after TMT, but not in CA3a, b, or the dentate gyrus. [3H]PZ binding was decreased throughout Ammon's horn by 14 d after treatment. [3H]OXO-M binding decreased 1 d after exposure in CA1 and in all subfields of Ammon's horn by d 3. Neither [3H]PZ or [3H]OXO-M binding decreased in the dentate gyrus of TMT-treated rat at any time point. The temporal patterns of receptor loss may be explicable by reference to timing of fiber and cell body degeneration reported in previous studies and the regional differences may account for discrepancies between reports of either substantial decreases or no loss in hippocampal muscarinic receptors after TMT exposure.

Animals↗

Effects of trimethyltin on acquisition and reversal of a light-dark discrimination by rats.

The behavioral deficits produced by trimethyltin (TMT) are usually attributed to the hippocampal damage caused by this toxicant. The purpose of this experiment was to determine the effects of TMT administration on acquisition and reversal of a discrete trial light-dark discrimination. Acquisition of this task is impaired by hippocampal lesions but the effects of TMT on it are not known. Forty-five days after some of the rats were given one of three doses of TMT, adult, male Long-Evans rats were given 100 trials per day for 20 days to acquire a discrete trial lever press discrimination with lit cue lights located above the correct lever. At the end of this time the contingencies were reversed and the rats were given 30 more days of training. No significant group differences occurred during the first 20 days. A significant group effect was found for the 30 days of reversal training. The rats given the highest dose of TMT (6 mg/kg) obtained significantly more reinforcements during reversal training than the other groups. Because surgical hippocampal lesions generally impair both acquisition and reversal of visual discriminations, these data were unexpected and suggest that other factors than hippocampal damage enter into the behavioral effects of TMT.

Animals↗

Localization of muscarinic receptor mRNAs in rat heart and intrinsic cardiac ganglia by in situ hybridization.

Although the heart is considered a relatively pure source of m2 muscarinic receptors, the possible expression of other muscarinic receptor genes at discrete sites within the myocardium or by intrinsic cardiac ganglia had not been evaluated. Accordingly, the present study used in situ hybridization histochemistry with 35S-labeled oligonucleotide probes to address this issue. Initial experiments demonstrated that the localization of m2 mRNA was similar to that reported for muscarinic receptors labeled with the nonselective muscarinic antagonist quinuclidinyl benzilate; however, there were two important exceptions. The conducting system contained less message than expected, whereas the intrinsic cardiac ganglia contained more. The mismatch between muscarinic receptor and m2 mRNA densities in the conducting system could not be explained by the local expression of other muscarinic receptor genes, since m1, m3, and m4 mRNAs were not detected at this or any other site within the myocardium. However, the presence of a high density of prejunctional muscarinic receptors in the conducting system would be consistent with such a mismatch. Surprisingly, the intrinsic cardiac ganglia contained more than four times as much m2 mRNA as found in the atria. This level of message may be necessary for the production of prejunctional receptors on cholinergic nerve fibers within the heart and receptors localized to the ganglion cell bodies. The ganglia also contained smaller amounts of m1 and m4 mRNAs. These observations suggest that prejunctional muscarinic receptors could have a prominent role in regulating cholinergic neurotransmission in the conducting system and that multiple muscarinic receptors are present in the intrinsic cardiac ganglia.

Animals↗

Transplant-induced working memory deficits in hippocampectomized rats.

This experiment determined the effects of transplantation of fetal hippocampus on the ability of male rats with hippocampal lesions to acquire versions of a radial arm maze that depended on either extramaze cues or intramaze cues for solution. Rats receiving transplants took significantly more trials than control rats to emit three consecutive errorless trials in the extramaze cue (spatial) variation of the maze. Rats with just hippocampal lesions never differed from any other group. No differences in this measure were found for the intramaze cue condition. Rats receiving transplants made more repeat entries into reinforced arms in both versions of the maze than control rats and more reentries into neverbaited arms in the spatial maze. Rats with hippocampal lesions failed to differ from any other group on this measure in the spatial maze, but were different from normal rats in the intramaze cue maze. These data suggest that in some tasks transplants of fetal tissue lead to greater behavioral impairment than lesions alone.

Animals↗

Angiotensin II binding sites in the hamster brain: localization and subtype distribution.

This study was designed to characterize the distribution of angiotensin II (AII) binding sites in the hamster brain. Brain sections were incubated with [125I][sar1,ile8]-angiotensin II in the absence and presence of angiotensin II receptor subtype selective compounds, losartan (AT1 subtype) and PD123177 (AT2 subtype). Binding was quantified by densitometric analysis of autoradiograms and localized by comparison with adjacent thionein stained sections. The distribution of AII binding sites was similar to that found in the rat, with some exceptions. [125I][sar1,ile8]-angiotensin II binding was not evident in the subthalamic nucleus and thalamic regions, inferior olive, suprachiasmatic nucleus, and piriform cortex of the hamster, regions of prominent binding in the rat brain. However, intense binding was observed in the interpeduncular nucleus and the medial habenula of the hamster, nuclei void of binding in the rat brain. Competition with receptor subtype selective compounds revealed a similar AII receptor subtype profile in brain regions where binding is evident in both species. One notable exception is the medial geniculate nucleus, predominately AT1 binding sites in the hamster but AT2 in the rat. Generally, the AII binding site distribution in the hamster brain parallels that of the other species studied, particularly in brain regions associated with cardiovascular and dipsogenic functions. Functional correlates for AII binding sites have not been elucidated in the majority of brain regions and species mismatches might provide clues in this regard.

Angiotensin II↗

Surface morphology of fetal neural transplants into the lateral ventricles after hippocampal lesions.

The surface morphology of transplants of rat fetal hippocampal tissue, and of cavities formed by aspiration lesion of the adult rat hippocampus and overlying neocortex into which the transplants were placed, was studied by scanning electron microscopy. The surface of lesion cavities was covered by a scar upon which occasional cellular profiles were found. The surface cells resembled supraependymal macrophages. Lesion cavities with a transplant showed similar scarring although the number of supraependymal structures was increased. Polymorphic cells and numerous fiber processes were observed both on the surface and embedded in the scar. Ependymal structures were seen on the non-damaged ventricular surfaces adjacent to the lesion site. These regions, however, also displayed increases in the number and types of supraependymal structures. Scanning electron microscopy demonstrated considerable variability in surface morphology of different transplants and over the surface of individual transplants. A transplant could show regions of scarring, areas covered by cells resembling ependymal cells, and regions covered by a dense matrix of fibers. In many regions the fibers coalesced to form a branching, web-like network over the transplant surface. Transmission electron microscopy indicated that the surface could be covered by ependymal cells or by the scar seen in scanning specimens. Some surface fibers were identified as axons. Cells on the surface of the transplants could be identified as neuronal, glial-like, and phagocytic. The cells and the possible effects of surface morphology on transplant function is discussed.

Animals↗

Effects of transplantation of fetal hippocampal or hindbrain tissue into the brains of adult rats with hippocampal lesions on water maze acquisition.

Rats were given bilateral aspiration lesions of the hippocampus. Some of these rats then received bilateral transplants of fetal hippocampal or dorsal ventricular ridge tissue that was dissected from embryonic rat brains at 16 or 17 days of gestation. The remaining rats with hippocampal lesions did not receive fetal brain transplants. Rats with neocortical aspiration lesions, but without transplants, and rats without brain damage were also included in the study. All of the rats were trained to find a submerged platform in a Morris water maze. Rats with the fetal brain transplants were more impaired in some measures of maze learning than were rats with hippocampal lesions only. The results indicate that transplants of fetal brain tissue are not always associated with recovery of behavioral function after brain damage and may even increase a lesion-induced behavioral impairment in tasks that require complex cognitive functioning.

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Neurochemical anatomy of fetal hippocampus transplanted into large lesion cavities made in the adult rat brain.

The purpose of the present study was to determine whether neurochemicals normally found within neuron somata, fibers, and terminals of the hippocampal formation would also be present in transplanted hippocampal tissue that had developed in lesion cavities made in adult rat brains by aspiration of the hippocampus and overlying dorsolateral neocortex. Embryonic Day 15 or 16 rat brian tissue containing hippocampus with some medial pallial anlage was transplanted into the site of hippocampal aspiration lesions in adult male rats. One hundred ten to one hundred thirty-five days later the brains of these rats were sectioned and processed using the avidin-biotin-horseradish peroxidase immunocytochemical procedure to visualize choline acetyltransferase, met-enkephalin (MENK), neurotensin (NT), somatostatin, substance P, tyrosine hydroxylase (TH), or vasoactive intestinal polypeptide. Sections from two brains were stained using the thiocholine technique for visualization of acetylcholinesterase. All of these substances were found within cell bodies and/or fibers in the transplants. However, several abnormalities were noted. In addition to TH-immunoreactive fibers, TH-immunoreactive cell bodies were found in the transplants. Since TH is not expressed in mature hippocampal or cortical neurons this suggests that mechanisms for suppression of manufacture of this enzyme are lacking or inhibited in the transplants. Further, although all of the peptides were present either in fibers or in both cell bodies and fibers, the density of staining for NT and MENK was less than would be expected for normal hippocampus, and none of the cell bodies or fibers reacting for the peptides exhibited any apparent organization resembling that normally observed in hippocampus or cortex. However, some histological organization was present and the cholinergic markers were associated with this organization. These data suggest that some tropic and/or trophic factor such as nerve growth factor is present in the transplants to guide cholinergic innervation.

Animals↗

Anatomical and behavioral sequelae of fetal brain transplants in rats with trimethyltin-induced neurodegeneration.

The effect of transplants of either fetal hippocampal or dorsal ventricular ridge (DVR) tissue into the brains of adult male rats exposed to TMT was determined for two behavioral tasks. Administration of TMT produced deficits in acquisition and performance of an operant differential reinforcement of low response rates (DRL) schedule and learning in the Morris water maze. The fetal transplants developed well within the TMT-damaged brains of the adult rats and numerous axons could be shown to cross the host-transplant interface. The transplants significantly reduced the DRL deficit produced by exposure to TMT. However, the TMT-induced deficit in water maze acquisition was made significantly worse by the hippocampal transplants. The improvement in DRL performance is attributed to the effect on the host brain of an unidentified trophic substance produced by the transplants. However, this positive effect may not protect the brain sufficiently to produce recovery in tasks demanding more complex neural computations than are required to withhold lever-press responses. The transplant-induced deficit observed in some aspects of water maze acquisition and performance may be attributable to either a tumor-like deleterious effect of the mass of the transplant or to abnormal neuronal activity transmitted from the transplant to the host brain. The results of the present study, and those from other similar studies, suggest that transplants of fetal tissue may be useful in producing changes in the brain of an animal exposed to an environmental neurotoxin, but that research should be focused upon development of transplant methodology that will minimize adverse effects of the grafts.

Animals↗

The effects of stimulation of the A5 region on blood pressure and heart rate in rabbits.

The effects of stimulation of the A5 cell group of the caudal ventrolateral pons electrically or with L-glutamate on heart rate and blood pressure were determined in rabbits. Electrical stimulation caused blood pressure increases and reflex bradycardia. L-glutamate caused decreases in blood pressure and heart rate which were blocked by the L-glutamate antagonist aminophosphoheptanoic acid. Transection of the brainstem at the level of the midbrain did not alter the effects of either electrical or chemical stimulation. Lesions of the nucleus and tractus solitarius (NTS) attenuated the effects of L-glutamate, but did not change the effectiveness of electrical stimulation. Injections of 6-hydroxydopamine three to four weeks before the experiments blocked the effects of electrical stimulation but only reduced the effects of L-glutamate injection. The A5 group may have two functional subdivisions. Some A5 cells may produce blood pressure depressor and bradycardic effects by means of projections to the NTS and the spinal cord. Other A5 cells may produce blood pressure pressor effects by means of projections to the spinal cord.

Animals↗

Grafts containing fetal hippocampal tissue reduce activity and improve passive avoidance in hippocampectomized or trimethyltin-exposed rats.

Embryonic Day 16 or 17 rat tissue containing either hippocampus with some medial pallial anlage or cerebellar/alar plate anlage was transplanted to the site of the ablated hippocampus of otherwise normal adult rats or adult rats previously exposed to the neurotoxin trimethyltin. Ninety to one hundred five days later these rats were compared to control rats in acquisition of passive avoidance and in open field activity. Transplantation of both types of tissue produced behavioral recovery on both tasks in rats with hippocampal lesions that had not been exposed to trimethyltin. Only hippocampal transplants produced recovery of function in rats given trimethyltin. Although transplants of hippocampal tissue had an organotypic structure that was easily differentiated with cell and fiber stains from that of the cerebellar transplants, neither of these routine histological procedures nor immunocytochemical analysis revealed differences between transplants made into normal rats or toxicant-exposed rats. Either of two mechanisms may account for the ability of the transplants to produce behavioral recovery. These are reconstruction of damaged circuitry by the transplant and neurotrophic action of the developing transplant on the host brain. The second mechanism alone may be sufficient to restore function in brain-lesioned but otherwise normal rats. Therefore, either type of transplant is effective. Both mechanisms may be necessary for recovery in brain-lesioned, toxicant-exposed rats. Therefore, only transplants of tissue homotypic to the tissue removed from the brain are effective.

Animals↗

Embryonic hippocampal grafts ameliorate the deficit in DRL acquisition produced by hippocampectomy.

Transplants of fetal neural tissue survive and develop in lesion cavities produced in adult rats. The present experiment tested the effect of grafting fetal hippocampal or brainstem tissue on the ability of rats with hippocampal lesions to perform on a differential reinforcement of low response rate (DRL) operant schedule. The DRL interval was 20s. Eighty-six percent of the hippocampal grafts and 69% of the brainstem grafts developed to maturity. Inspection of sections from rats in which the mature transplant had been injected with Fast blue, indicated that these grafts formed connections with the host brain. Consistent with previous reports, rats with hippocampal lesions were impaired in performance of the DRL task. Rats given fetal grafts of hippocampal tissue into the hippocampal lesion site on the day of lesion production were significantly better in performance of the DRL requirement than were lesion-only rats or rats receiving grafts of fetal brainstem tissue. The results of this study confirm that grafts of fetal brain tissue can both develop in a lesion site in an adult brain and ameliorate lesion-induced behavioral deficits.

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Cells of origin of the branches of the facial nerve: a retrograde HRP study in the rabbit.

The origin of different branches of the facial nerve in the rabbit was determined by using retrograde transport of HRP. Either the proximal stump of specific nerves was exposed to HRP after transection, or an injection of the tracer was made into particular muscles innervated by a branch of the facial nerve. A clear somatotopic pattern was observed. Those branches which innervate the rostral facial musculature arise from cells located in the lateral and intermediate portions of the nuclear complex. Orbital musculature is supplied by neurons in the dorsal portion of the complex, with the more rostral orbital muscles receiving input from more laterally located cells while the caudal orbital region receives innervation from more medial regions of the dorsal facial nucleus. The rostral portion of the ear also receives innervation from cells located in the dorsomedial part of the nucleus, but the caudal aspect of the ear is supplied exclusively by cells located in medial regions. The cervical platysma, the platysma of the lower jaw, and the deep muscles (i.e., digastric and stylohyoid) receive input from cells topographically arranged in the middle and ventral portions of the nuclear complex. It is proposed that the topographic relationship between the facial nucleus and branches of the facial nerve reflects the embryological derivation of the facial muscles. Those muscles that develop from the embryonic sphincter colli profundus layer are innervated by lateral and dorsomedial portions of the nuclear complex. The muscles derived from the embryonic platysma layer, including the deep musculature, receive their input from mid to ventral regions of the nuclear complex.

Animals↗

Effects of electrical stimulation of the pontine A5 cell group on blood pressure and heart rate in the rabbit.

The effects of electrical stimulation of the A5 noradrenergic cell group of the ventrolateral pons was assessed in rabbits. Stimulation administered through either concentric bipolar or monopolar electrodes produced current-intensity related increases in mean arterial pressure (MAP). Decreases in heart rate (HR) accompanied the increases in MAP, but were essentially eliminated by bilateral vagotomy or destruction of the nucleus and tractus solitarii (NTS), thereby indicating that the HR decelerations were secondary to activation of baroreceptor reflexes. Neither vagotomy nor midcollicular section of the brainstem altered the MAP response to A5 stimulation. Bilateral destruction of the NTS slightly enhanced the response. Several rabbits received microinjections of 6-hydroxydopamine (6-OHDA) into the A5 region 2 weeks before the experiment. Other rabbits received vehicle injections and served as control subjects for the non-specific effects of the 6-OHDA injections. 6-OHDA injections, but not vehicle injections, prevented the vasopressor effects of A5 stimulation. However, stimulation of the A1 noradrenergic nucleus of the ventrolateral medulla produced decreases in MAP in rabbits given prior microinjections of 6-OHDA into A5. These observations are interpreted to indicate that the 6-OHDA injections produced neurotoxic effects which were relatively restricted to the A5 region. Furthermore, the data from all of these experiments are interpreted as indicating that the vasopressor effects observed as a consequence of electrical stimulation of A5 are due to excitation of the noradrenaline-containing neuron cell bodies of this region and that this effect is mediated via pathways arising from this region and terminating in the intermediolateral cell column of the spinal cord.

Adrenergic Fibers↗

Expansion of the ipsilateral retinal projection to the medial terminal nucleus of the accessory optic system in rats with one eye removed.

Expansion of ipsilateral retinal inputs into terminal regions of the accessory optic system was assessed in rats with one eye removed either at birth or as adults and in one animal with a congenital absence of one eye. The increase in the ipsilateral projection to the medial terminal nucleus in animals receiving unilateral enucleation at birth was greater than after eye removal as an adult. The greatest increase was observed in the animal with the congenital loss of one eye. No ipsilateral projection to other nuclei of the accessory optic system was observed.

Animals↗