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Evidence for a glutamatergic projection from the zona incerta to the basal ganglia of rats.

This study explores the organisation and neurochemical nature of the projections from the zona incerta (ZI) to the basal ganglia. Sprague-Dawley rats were anaesthetised with ketamine (100 mg/kg) and Rompun (10 mg/kg), and injections of cholera toxin subunit B were made into each of the following nuclei: the ZI, the substantia nigra (SN), the pedunculopontine tegmental nucleus (PpT), and the entopeduncular nucleus (Ep). Brains were aldehyde fixed, sectioned, and processed using standard methods. Tracer-labelled sections were then doubly labelled with antibodies to glutamate (Glu), nitric oxide synthase (NOS), parvalbumin (Pv), or glutamic acid decarboxylase (GAD; the latter two are markers for GABAergic cells); these neurochemicals characterise most types of ZI cells. After ZI injections, labelling was nonuniform across the different basal ganglia nuclei. The bulk of labelling, both anterograde and retrograde, was seen in the SN and PpT and, to a lesser extent, within the other nuclei of the basal ganglia (e.g., caudate-putamen, globus pallidus, subthalamus, Ep). In the SN, labelling was found in both major parts of the nucleus, the pars compacta and pars reticulata. Within the PpT, however, the bulk of labelling was limited to only one of the two sectors of the nucleus, namely, the pars dissipata (PpTd). The pars compacta of the PpT (PpTc) remained largely free of labelled profiles. After CTb injections into three basal ganglia nuclei (SN, PpT, Ep), most labelled cells in the ZI were glutamate+ and very few were NOS+ or gamma-aminobutyric acidergic. Overall, the results indicate that the ZI is in a position to influence preferentially the activity of the SN and PpTd of the basal ganglia via an excitatory, glutamatergic input.

Animals↗

Proliferative and degenerative events in the early development of chick dorsal root ganglia. II. Responses to altered peripheral fields.

Responses of chick embryo dorsal root ganglia to early wing bud amputation were examined histologically using tritiated thymidine (3H-TdR) and autoradiography to analyze proliferation and the Feulgen procedure to visualize degenerating cells. Right wing buds were amputated at stage 15 or 16. At 4.5 to 9.5 days of incubation embryos were given a 1-hour exposure to 3H-TdR and fixed. Feulgen-stained autoradiographs were examined for percentage of cells labelled (labelling index) or degenerating (degeneration index) in lateroventral (LV) and mediodorsal (MD) regions of brachial (G14-16) and nonbrachial (G12, 13, 17) ganglia. The earliest response to amputation was a highly significant increase in degeneration indices of LV and MD regions of ipsilateral brachial ganglia at 5.5 days. Significant brachial LV responses were observed throughout the remainder of the experimental period. Two peaks occur in this response: at 5.5 days, corresponding to the peak seen in normal nonbrachial ganglia, and at 8.5 days, having no counterpart in normal development. In brachial MD regions significant degenerative responses occur at most times examined. Significant responses also occur at 7.5 and 8.5 days in MD regions of nonbrachial ganglia. The presence of MD responses in our material indicates that maturation of at least some MD neurons occurs earlier than previously thought. Significant labelling responses occur in brachial LV regions from 7.5 days on. Because other studies (Carr and Simpson, '78a) show that this time is after the end of large-scale neuronal production, this labelling response must be nonneuronal in nature. We conclude that this response is a secondary response to amputation, consequent to the greatly increased cellular degeneration. Results of experiments involving addition of limb buds at the brachial level are also presented.

Amputation, Surgical↗

The architecture of nerves and ganglia of the ferret trachea as revealed by acetylcholinesterase histochemistry.

The goal of this study was to determine the architecture of the nerves and ganglia of the ferret trachea. Tracheas from four newborn ferrets and three adult ferrets were stained histochemically for acetylcholinesterase activity and analyzed in their entirety as whole mounts. The architecture consisted of one or two longitudinal nerve trunks overlying the posterior surface of the trachealis muscle, a dense plexus of nerves superficial to the trachealis muscle that interconnected these longitudinal nerve trunks, and, on the anterior surface, a plexus superficial to the submucosal glands and located between the cartilaginous rings. In addition, deep neural plexuses were associated with the trachealis muscle and with the submucosal glands. Ganglion cell bodies along the longitudinal nerve trunks were large (mean diameter +/- S.E. = 34.3 +/- 0.3 microns), were usually attached to the nerve trunk by a stalk, and were loosely clustered in groups of as many 38 cell bodies. By contrast, those cell bodies of the superficial muscle and gland plexuses were significantly smaller (mean diameter +/- S.E. = 24.2 +/- 0.3 microns), were never attached by a stalk, and were tightly clustered in ganglia of one to four cell bodies. We conclude that nerves and ganglia of the ferret trachea constitute one or two longitudinal nerve trunks containing ganglia with large cell bodies, two superficial nerve plexuses containing ganglia with small cell bodies overlying the smooth muscle and submucosal glands, respectively, and two deep nerve plexuses providing the terminal innervation to the muscle and glands.

Acetylcholinesterase↗

Segmental differentiation in the leech nervous system: the genesis of cell number in the segmental ganglia of Haemopis marmorata.

In hirudinid leeches, the segmental ganglia associated with the sexual organs contain several hundred more neurons than other midbody ganglia. To determine whether this difference arises by differential cell addition or by differential cell death, cell counts were made in several segmental ganglia during the course of embryonic and postembryonic development. The results show that all ganglia behave equally in early development. In each case, at least 10-20% more cells than will make up the adult complement of about 400 neurons is generated, and by about 20 days of embryonic development cell loss brings the number down to about 400 cells. By about 30 days, when animals emerge from their cocoons, additional cells have begun to appear in the sex ganglia. The number of extra cells continue to increase gradually over the next several months, until the adult number of 600-700 neurons is attained. These observations indicate that at least some segmental differences in the size of neuronal populations are due to differential cell proliferation and that these differences can arise quite late in the maturation of an animal.

Animals↗

Pedunculopontine nucleus in the squirrel monkey: projections to the basal ganglia as revealed by anterograde tract-tracing methods.

The efferent projections of the pedunculopontine nucleus (PPN) to the basal ganglia have been studied in the squirrel monkey (Saimiri sciureus) with [3H]leucine and Phaseolus vulgaris-leucoagglutinin (PHA-L) as anterograde tracers. Following unilateral injections of [3H]leucine or PHA-L in the central portion of the PPN, numerous autoradiographic linear profiles or PHA-L-labeled fibers ascend to the forebrain, both ipsilaterally and contralaterally. These fibers form a compact bundle that courses in the central portion of the mesopontine tegmentum. At rostral mesencephalic levels, this bundle splits into ventromedial and dorsolateral fascicles that arborize in basal ganglia and thalamic nuclei, respectively. The substantia nigra and the subthalamic nucleus are by far the most densely innervated structures of the basal ganglia. In these two nuclei, labeled fibers arborize profusely ipsilaterally and less abundantly contralaterally. The labeled fibers in the substantia nigra are thin and varicose and arborize almost exclusively in the pars compacta, where they closely surround the soma and proximal dendrites of dopaminergic neurons. In the subthalamic nucleus, labeled fibers are also thin and appear to contact more than one neuron along their course. Numerous labeled fibers also occur in the pallidal complex, where they arborize most profusely in the internal segment. Several thick, labeled fibers oriented dorsolaterally in the pallidal complex give rise to thinner fibers that closely surround the soma and proximal dendrites of pallidal neurons. Some labeled fibers are also scattered in the striatum. These fibers abound in the peripallidal and ventral portions of the putamen, are more sparsely distributed in the remaining portion of the putamen as well as in the caudate nucleus, and are virtually absent in the ventral striatum. These results reveal that the PPN gives rise to a massive and highly ordered innervation of the basal ganglia in the squirrel monkey. This nucleus may thus act as an important relay in the basal ganglia circuitry in primates.

Animals↗

Cadherin-2 function in the cranial ganglia and lateral line system of developing zebrafish.

Cadherins are cell surface molecules that mediate cell-cell adhesion through homophilic interactions. Cadherin-2 (also called N-cadherin), a member of classic cadherin subfamily, has been shown to play important roles in development of a variety of tissues and organs, including the nervous system. We recently reported that cadherin-2 was strongly expressed by the majority of cranial ganglia and lateral line system of developing zebrafish. To gain insight into cadherin-2 role in the formation of these structures, we have used several markers to analyze zebrafish embryos injected with a specific cadherin-2 antisense morpholino oligonucleotide (cdh2MO). We find that development of several cranial ganglia, including the trigeminal, facial, and vagal ganglia, and the lateral line ganglia and neuromasts of the cdh2MO-injected embryos are severely disrupted. These phenotypes were confirmed by analyzing a cadherin-2 mutant, glass onion. Our results suggest that cadherin-2 function is crucial for the normal formation of the zebrafish lateral line system and a subset of cranial ganglia.

Animals↗

Localization of calretinin in the rat ovary and in relation to nerve cell bodies in dorsal root and paravertebral ganglia projecting to the ovary.

Retrograde tracing with True Blue was combined with immunocytochemistry to determine the source of any calretinin-immunoreactive (CR-ir) nerves projecting to the rat ovary. In the ovary, a strong signal for calretinin immunoreactivity was localized in interstitial gland cells; however, no intraovarian CR-ir nerves could be demonstrated. When the superior ovarian nerve was isolated, cut, and True Blue applied to the proximal end, the fluorescent dye was retrogradely transported to a population of cells located in T-12, T-13, and L-1 dorsal root and paravertebral ganglia. There was virtually no dual labeling of cells in these ganglia with calretinin (< 0.009% dual labeling in dorsal root and <0.014% in paravertebral ganglia). However, greater than two-thirds of the True Blue-labeled cells were immediately adjacent to CR-ir cells in dorsal root ganglia. This arrangement is suggestive of a paracrine mechanism between CR-ir cells and cells projecting to the ovary. In paravertebral ganglia, 63% of cells projecting to the ovary were surrounded completely or partially by beaded CR-ir nerve fibers. The source of these fibers (sensory or preganglionic sympathetic) is unknown but hypothesized to be preganglionic. Collectively, these observations suggest a participatory role for calretinin in ovarian function, either directly via effects on the interstitial gland or indirectly by influencing neurons projecting to the ovary.

Animals↗

Immunohistochemical demonstration of galanin-, and galanin message-associated peptide-like immunoreactivities in sympathetic ganglia and adrenal gland of the guinea pig.

Using the indirect immunofluorescence method, the distribution of galanin (GAL)- and galanin message-associated peptide (GMAP)-like immunoreactivities (LI) were studied in sympathetic ganglia and the adrenal gland of the guinea pig. A rather dense network of GAL-immunoreactive nerve fibers was found in the inferior mesenteric ganglion (IMG) and in the superior mesenteric pole of the celiac-superior mesenteric ganglion complex (C-SMG). The celiac pole of the C-SMG, the stellate ganglion, and the superior cervical ganglion contained fewer, mostly scattered fibers. SIF-cells in prevertebral and paravertebral ganglia contained GAL-LI, as did the adrenal medullary cells. The GAL fibers in the IMG surrounded mainly principal ganglion cells containing somatostatin-immunoreactivity (SOM-IR), whereas fewer fibers were seen around neuropeptide Y (NPY) cells and cells in which SOM and NPY coexisted. Application of colchicine or vinblastine onto the IMG did not result in the appearance of GAL-IR in the principal ganglion cells. In denervation experiments it was revealed that most of the GAL fibers reach the IMG via the lumbar splanchnic nerves. GAL-IR appears to be colocalized with substance P (SP) in fibers of the IMG, indicating an origin of the GAL-containing fibers in dorsal root ganglia (DRG). This conclusion was supported by the finding in lumbar DRGs of GAL-positive cell bodies that contained SP. The role of GAL in prevertebral ganglia is unclear. It may be suggested that GAL modulates the slow, long-lasting membrane depolarization of the principal ganglion cells caused by SP in the primary afferents related to the IMG. GMAP-LI was detected in SIF cells and adrenal medullary cells in which GMAP-LI parallels the immunoreactivity of GAL. GMAP-LI was not observed in neuronal cell bodies or nerve fibers of the ganglia.

Adrenal Glands↗

Development of extracellular matrix in chick paravertebral sympathetic ganglia.

Alcian blue staining coupled with enzyme digestion or critical electrolyte staining revealed differences in the development of extracellular matrix (ECM) within sympathetic ganglia compared with the surrounding capsule. On day 5 of chick development (Hamburger-Hamilton stage 26) only hyaluronic acid (HA) could be detected in the ECM surrounding condensing primary ganglia. By day 7 (st 30) the ganglionic capsule contained HA, as well as sulfated glycosaminoglycans (GAGs), and this pattern continued into the adult stage. During the later stages of embryonic life (st 41-45) satellite cells appear, showing fine structural characteristics that point to their role in the secretion of intraganglionic ECM. Only during these stages could ECM be detected histochemically within ganglia, the same stages (days 15-19) when routine electron microscopic methods reveal collagen fibrils embedded in a granular ground substance. Thus, the intraganglionic environment appears as a separate compartment free of detectable amounts of GAG until late embryonic stages when ECM is secreted around satellite cells. This developmental pattern could represent a role of ECM in the histological stabilization of ganglia during the late stages of differentiation, since the appearance of intraganglionic ECM is correlated with the appearance of small dense-cored vesicles characteristic of adult neurons. The developmental pattern of ECM in differentiating sympathetic ganglia is compared with that of other tissues that undergo condensation and morphogenesis.

Animals↗

DNA microarray cluster analysis reveals tissue similarity and potential neuron-specific genes expressed in cranial sensory ganglia.

Each of four cranial sensory ganglia, trigeminal, geniculate, petrosal, and nodose ganglia, contains multiple kinds of sensory neurons with different cell morphologies and neuronal properties that transmit information about sensory stimuli received peripherally. Here we analyze the complex properties of these neurons from the viewpoint of gene expression using DNA microarrays by cluster analysis. From a total of 8,740 genes, 498 genes were selected as showing tissue-dependent expression on the microarray by hierarchical cluster analysis, and their profiles indicated that, among the four sensory ganglia, the petrosal and trigeminal ganglia are intimately related. Tissue trees of 37 subclusters containing the 498 genes showed that the profiles of gene expression and the subclusters were classified into a smaller number of groups (18 groups) when information on the amounts of expression was added. In situ hybridization analysis of 21 genes selected from 13 different groups was carried out, and the gene expression patterns were classified into eight categories. The putative profiles postulated from the microarray data were essentially consistent with the patterns of expression at the cellular level as shown by in situ hybridization. In conclusion, from the overall analyses of gene expression by DNA microarray, we can identify a number of candidate genes showing neuron type-specific expression in the peripheral ganglia.

Animals↗

Selective modulation of cholinergic properties in cultures of avian embryonic sympathetic ganglia.

We have studied the expression of catecholaminergic and cholinergic phenotypes in sympathetic ganglia removed from 7- to 10-day-old quail embryos and grown in vitro under different conditions. Quantitative data were obtained by measuring the conversion of (3H) tyrosine and (3H) choline to catecholamines (CA) and acetylcholine (ACh), respectively. In explant cultures, large amounts of both neurotransmitters were synthesized from the onset, but CA generally predominated, the molar ratios of CA:ACh being, on average, of the order of 2:1. If the ganglia were dissociated before plating, there was a selective increase in ACh synthesis (three- to fivefold) such that the CA:ACh ratio fell strikingly. The early expression of the cholinergic phenotype appears to be species-specific in that, under identical conditions, dissociated cell cultures of newborn mouse superior cervical ganglia were overwhelmingly catecholaminergic (CA:ACh ratio of approximately 40:1) and ACh synthesis was only just detectable. Addition of veratridine (1.5 microM) either to explant or to dissociated cell cultures of embryonic quail sympathetic ganglia barely altered CA-synthesizing ability; in contrast, ACh synthesis and accumulation were stimulated about threefold. This effect, which we found to correspond to a quantitatively similar increase in the activity of choline acetyltransferase (ChAT), was completely blocked by tetrodotoxin, indicating that it was due to Na(+)-dependent depolarization. A preferential stimulation of ACh production was also observed when the concentration of K+ was raised to 20 mM. Veratridine treatment of cultures of presumptive sympathoblasts, in the form of sclerotome-associated neural crest cells, had identical effects. Our results reveal the quantitative importance of ACh-related properties in avian sympathetic ganglia from the earliest stages of their development and suggest that depolarization may be one of the factors selectively enhancing expression of the cholinergic phenotype during ontogeny. In these respects, the neurochemical differentiation of sympathetic neurons unfolds according to dissimilar scenarios in birds and mammals.

Acetylcholine↗

Oscillations in the basal ganglia under normal conditions and in movement disorders.

A substantial body of work within the last decade has demonstrated that there is a variety of oscillatory phenomena that occur in the basal ganglia and in associated regions of the thalamus and cortex. Most of the earlier studies focused on recordings in rodents and primates. More recently, significant advances have been made in this field of research through the analysis of basal ganglia field potentials recorded from implanted deep brain stimulation electrodes in the basal ganglia of human patients with Parkinson's disease and other disorders. It now appears that oscillatory activity may play a significant role in the pathogenesis of these diseases. The most significant finding is that in Parkinson's disease synchronized oscillatory activity in the 10- to 35-Hz band (often termed "beta-band") is prevalent in the basal ganglia-thalamocortical circuits, and that such activity can be reduced by dopaminergic treatments. The entrainment of large portions of these circuits may disrupt information processing in them and may lead to parkinsonian akinesia (and perhaps tremor). Although less firmly established than the role of oscillations in movement disorders, oscillatory activities at higher frequencies may also be a component of normal basal ganglia physiology.

Animals↗

Acute movement disorders with bilateral basal ganglia lesions in uremia.

Acute and subacute extrapyramidal movement disorders are rarely reported in uremic patients. We report three such cases with basal ganglia lesions. All three had advanced renal failure with high serum creatinine levels. One of the patients had a history of ischemic heart disease and acute pulmonary edema with hypoxemia. Another patient had experienced arterial hypotension during previous hemodialysis. The third had prominent metabolic acidosis. One of the patients developed generalized dyskinesias, whereas the other two developed gait disturbances. Neuroimaging studies in all three cases showed bilateral changes in the basal ganglia. The natural history was self-limiting with gradual improvement. Diminution of the basal ganglia lesions was demonstrated on follow-up imaging in two of the three cases. We conclude that acute or subacute movement disorders with bilateral basal ganglia lesions may occur in uremia. Hypoperfusion with global brain ischemia and selective vulnerability of the basal ganglia to uremic toxins may account for these lesions.

Acute Disease↗

Dose and behavioral context dependent inhibition of movement and basal ganglia neural activity by Delta-9-tetrahydrocannabinol during spontaneous and treadmill locomotion tasks in rats.

The effects of Delta-9-tetrahydrocannabinole (Delta-9-THC) on locomotor activities and related basal ganglia neural responses were investigated in rats. A multiple-channel, single unit recording method was used to record neuronal activity in the dorsal lateral striatum, the globus pallidus, the subthalamic nucleus, and the substantia nigra pars reticulata simultaneously during spontaneous movement and treadmill locomotion. Delta-9-THC treatment (0.05-2.0 mg/kg, i.p.) dose-dependently decreased spontaneous motor activity and altered walking patterns in treadmill locomotion in that stance time was increased and step number was decreased. In parallel with the behavioral effects, Delta-9-THC treatment inhibited neural activity across all four basal ganglia areas recorded during both motor tests. Further, this inhibition of basal ganglia neural activity was behavioral context-dependent. Greater inhibition was found during resting than during walking periods in the treadmill locomotion test. Delta-9-THC treatment also changed firing patterns in the striatum and globus pallidus. More neurons in these regions discharged in an oscillatory pattern during treadmill walking with Delta-9-THC, and the oscillatory frequency was similar to that of the step cycle. Synchronized firing patterns were found in few basal ganglia neurons in the control condition (approximately 1%). Synchronized firing patterns increased during the treadmill resting phase after Delta-9-THC treatment, but still represented a very small proportion of the total neural population (1.9%). The drug treatment did not change neural responses to the tone cue proceeding treadmill locomotion. This study demonstrates dose-dependent inhibitory effects of cannabinoid injection on motor activity. This effect may be related to the behavioral context-dependent inhibition observed in the basal ganglia system where CB1 receptors are densely distributed.

Action Potentials↗

Serotonin-induced increase in cAMP in ganglia isolated from the myenteric plexus of the guinea pig small intestine: mediation by a novel 5-HT receptor.

Serotonin (5-HT) is a mediator (through 5-HT1P receptors) of slow EPSPs in myenteric ganglia of the small intestine. The effect of 5-HT can be mimicked by elevating cAMP; therefore, we tested the hypothesis that the slow EPSP-like response to 5-HT is cAMP-mediated. Guinea pig gut was enzymatically dissociated; myenteric ganglia remained intact and were collected by filtration. Neurons in the isolated ganglia retained their ability to manifest the slow EPSP-like response to 5-HT. Exposure to 5-HT raised the ganglionic level of cAMP (ED50 0.3 microM). This effect was not antagonized by the 5-HT1P antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (100.0 microM), or mimicked by the 5-HT1P agonist, 5-hydroxyindalpine (10.0 microM). Increases in cAMP were also evoked by the 5-HT1 agonist, 5-carboxyamidotryptamine (10.0 microM), the 5-HT2 agonist, (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 1.0-10.0 microM), and by the 5-HT4 agonists, renzapride (1.0-10.0 microM) and 5-methoxytryptamine (1.0-10.0 microM); however, neither the 5-HT1/5-HT2 antagonists, spiperone, methysergide, and methiothepin, nor the 5-HT4 antagonist, tropisetron (ICS 205-930; 10.0 microM), were able to inhibit the rise in cAMP evoked by these compounds or by 5-HT (0.1-10.0 microM). The 5-HT-evoked elevation of cAMP was antagonized by ketanserin (10.0 microM), which also blocked the effects of 5-methoxytryptamine and DOI, but not those of renzapride. The effective concentration of DOI, however, was higher than that needed for activation of 5-HT2 receptors, and Northern analysis using a cDNA probe encoding the rat 5-HT2 receptor failed to reveal the presence of 5-HT2 mRNA in myenteric ganglia, although it hybridizes with mRNA of the right size in the guinea pig brain. Compounds that failed to change levels of cAMP or to antagonize the action of 5-HT included 8-hydroxy-di-n-propylamino tetralin, R58639, R88226, and sumatriptan. It is concluded that the receptor responsible for the 5-HT-induced rise in cAMP in ganglia isolated from the guinea pig myenteric plexus is not a known subtype of 5-HT receptor. Since the pharmacology of this novel receptor is different from that of the slow EPSP-like response to 5-HT, the receptor probably does not mediate the slow EPSP.

Acetylcholinesterase↗

Spinal ganglia reduction in the splotch-delayed mouse neural tube defect mutant.

Splotch and splotch-delayed mutants have anomalies in certain neural crest cell derivatives as well as neural tube defects. A genetic marker was used to identify mutant, heterozygote, and wild-type embryos within a litter, which enabled us to make intergenotypic comparisons. Histological studies of the lumbosacral region of day 15 and day 16 embryos indicated that the splotch-delayed mutant had similar but less severe defects in spinal ganglion development than those reported for splotch (Auerbach: Journal of Experimental Zoology 127:305-329, 1954). The ganglia were extensively reduced in size, residual, or missing in the splotch-delayed mutant, whereas in the splotch mutant, they were virtually nonexistent. Paired comparison analyses showed that all mutant embryos had a significant reduction in their volume of lumbosacral spinal ganglia when compared to their heterozygous and/or wild-type littermates. Also, some heterozygotes were found to have spinal ganglia volumes that were significantly reduced when compared to wild-type embryos. The volume of spinal ganglia was not related to the severity of the neural tube defect. In fact, three mutant embryos, which did not exhibit a neural tube defect, had spinal ganglia volumes comparable to or less than those mutants with open neural tube lesions or curly tails. This shows that the formation of abnormal neural crest cell derivatives is not a result of the neural tube closure defect. We hypothesize that the two anomalies observed in these mutants have a common etiological basis.

Animals↗

Sacral neural crest cells colonise aganglionic hindgut in vivo but fail to compensate for lack of enteric ganglia.

The vagal neural crest is the origin of majority of neurons and glia that constitute the enteric nervous system, the intrinsic innervation of the gut. We have recently confirmed that a second region of the neuraxis, the sacral neural crest, also contributes to the enteric neuronal and glial populations of both the myenteric and the submucosal plexuses in the chick, caudal to the level of the umbilicus. Results from this previous study showed that sacral neural crest-derived precursors colonised the gut in significant numbers only 4 days after vagal-derived cells had completed their migration along the entire length of the gut. This observation suggested that in order to migrate into the hindgut and differentiate into enteric neurons and glia, sacral neural crest cells may require an interaction with vagal-derived cells or with factors or signalling molecules released by them or their progeny. This interdependence may also explain the inability of sacral neural crest cells to compensate for the lack of ganglia in the terminal hindgut of Hirschsprung's disease in humans or aganglionic megacolon in animals. To investigate the possible interrelationship between sacral and vagal-derived neural crest cells within the hindgut, we mapped the contribution of various vagal neural crest regions to the gut and then ablated appropriate sections of chick vagal neural crest to interrupt the migration of enteric nervous system precursor cells and thus create an aganglionic hindgut model in vivo. In these same ablated animals, the sacral level neural axis was removed and replaced with the equivalent tissue from quail embryos, thus enabling us to document, using cell-specific antibodies, the migration and differentiation of sacral crest-derived cells. Results showed that the vagal neural crest contributed precursors to the enteric nervous system in a regionalised manner. When quail-chick grafts of the neural tube adjacent to somites 1-2 were performed, neural crest cells were found in enteric ganglia throughout the preumbilical gut. These cells were most numerous in the esophagus, sparse in the preumbilical intestine, and absent in the postumbilical gut. When similar grafts adjacent to somites 3-5 or 3-6 were carried out, crest cells were found within enteric ganglia along the entire gut, from the proximal esophagus to the distal colon. Vagal neural crest grafts adjacent to somites 6-7 showed that crest cells from this region were distributed along a caudal-rostral gradient, being most numerous in the hindgut, less so in the intestine, and absent in the proximal foregut. In order to generate aneural hindgut in vivo, it was necessary to ablate the vagal neural crest adjacent to somites 3-6, prior to the 13-somite stage of development. When such ablations were performed, the hindgut, and in some cases also the cecal region, lacked enteric ganglionated plexuses. Sacral neural crest grafting in these vagal neural crest ablated chicks showed that sacral cells migrated along normal, previously described hindgut pathways and formed isolated ganglia containing neurons and glia at the levels of the presumptive myenteric and submucosal plexuses. Comparison between vagal neural crest-ablated and nonablated control animals demonstrated that sacral-derived cells migrated into the gut and differentiated into neurons in higher numbers in the ablated animals than in controls. However, the increase in numbers of sacral neural crest-derived neurons within the hindgut did not appear to be sufficiently high to compensate for the lack of vagal-derived enteric plexuses, as ganglia containing sacral neural crest-derived neurons and glia were small and infrequent. Our findings suggest that the neuronal fate of a relatively fixed subpopulation of sacral neural crest cells may be predetermined as these cells neither require the presence of vagal-derived enteric precursors in order to colonise the hindgut, nor are capable of dramatically altering their proliferation or d

Animals↗

The basal ganglia and chunking of action repertoires.

The basal ganglia have been shown to contribute to habit and stimulus-response (S-R) learning. These forms of learning have the property of slow acquisition and, in humans, can occur without conscious awareness. This paper proposes that one aspect of basal ganglia-based learning is the recoding of cortically derived information within the striatum. Modular corticostriatal projection patterns, demonstrated experimentally, are viewed as producing recoded templates suitable for the gradual selection of new input-output relations in cortico-basal ganglia loops. Recordings from striatal projection neurons and interneurons show that activity patterns in the striatum are modified gradually during the course of S-R learning. It is proposed that this recoding within the striatum can chunk the representations of motor and cognitive action sequences so that they can be implemented as performance units. This scheme generalizes Miller's notion of information chunking to action control. The formation and the efficient implementation of action chunks are viewed as being based on predictive signals. It is suggested that information chunking provides a mechanism for the acquisition and the expression of action repertoires that, without such information compression would be biologically unwieldy or difficult to implement. The learning and memory functions of the basal ganglia are thus seen as core features of the basal ganglia's influence on motor and cognitive pattern generators.

Animals↗