Calcitonin gene-related peptide (CGRP) immunoreactive projections from the thalamus to the striatum and amygdala in the rat

The organization of calcitonin gene-related peptide-like immunoreactive (CGRPir) innervation of the amygdala and caudate-putamen in the rat was examined by using immunohistochemistry for CGRP combined with retrograde transport of the fluorescent dye fluoro-gold, as well as anterograde transport of Phaseoleus vulgaris leucoagglutinin (PHA-L). The lateral part of the central nucleus of the amygdala and the amygdalostriatal transition zone was densely innervated by CGRPir terminals at all anterior-posterior levels. More caudally, the lateral part of the caudate-putamen also had large numbers of CGRPir terminals. Injections of fluoro-gold into the amygdala and amygdalostriatal transition area followed by immunohistochemistry for CGRP revealed double-labeled neurons in the subparafascicular, lateral subparafascicular, and posterior intralaminar nuclei of the thalamus and peripeduncular nucleus. Injections into the caudate-putamen demonstrated double-labeled neurons in the more lateral parts of this same nuclear complex. PHA-L injections into the posterior thalamic nuclei from which the CGRPir projections arise confirmed the medial-to-lateral organization of the projections to the amygdala and striatum. The subparafascicular nucleus and the rostral portion of the lateral subparafascicular nucleus primarily projected to the medial amygdala and the amygdalostriatal transition area, while the more lateral cell groups, including the caudal part of the lateral parafascicular, posterior intralaminar, and peripeduncular nuclei projected to the lateral amygdala and the caudate-putamen. These CGRPir projections may be involved in mediating conditioned autonomic and behavioral responses to acoustic stimuli or somatosensory stimuli.     

Connections between cells of the internal capsule,thalamus, and cerebral cortex in embryonic rat

The aim of our study is to understand the development of the earliest connections in the mammalian pallium by documenting the distribution of cells and fibres labelled from the dorsal and ventral thalamus, internal capsule, perirhinal, and dorsal cortex during the period between embryonic day (E) 14 and 17 by using carbocyanine dye tracing in fixed embryonic rat brains. Dye placed in the thalamus of E14 brains backlabels cells in the thalamic reticular nucleus and within the primitive internal capsule. Both anterograde and retrograde tracing confirmed that the first corticofugal projections reach the internal capsule by E14. At E15–E16, after the first cortical plate cells have migrated into the lateral cortex, some cells of the cortical plate and subplate and marginal zone, are backlabelled from the internal capsule, but still not from the dorsal thalamus, even with very long incubation periods. Crystal placement into the perirhinal cortex at E14–E15 labels numerous cells within the internal capsule, whereas no such cells are revealed from dorsal cerebral cortex until E17, suggesting that internal capsule cells establish early connections with the perirhinal and ventral but not dorsal cortex. We propose that the growth of axons from cortex to dorsal thalamus is delayed in two regions: first from E14–E15 at the lateral entrance of the internal capsule and then, from E16, closer to the thalamus, probably within the thalamic reticular nucleus. Subplate projections reach the proximity of the diencephalon at an early stage, but they might never enter the dorsal thalamus. J. Comp. Neurol. 413:1–25, 1999. © 1999 Wiley-Liss, Inc.     

Calcitonin gene-related peptide projection from the ventromedial thalamic nucleus to the insular cortex: a combined retrograde transport and immunocytochemical study

We employed a highly sensitive combination method of retrograde tracing and immunohistochemistry to identify calcitonin gene-related peptide (CGRP)-containing fiber pathways in the rat from the ventrolateral part of the ventrolateral thalamic nucleus (vl-vl) and the caudal continuation to the insular cortex. Biotin-wheat germ agglutinin (B-WGA) injected into the insular cortex labeled numerous neurons in the vl-vl and the caudal continuation ipsilaterally; simultaneous staining with CGRP antiserum revealed that some of these neurons are CGRP positive.     

Fine structure of calcitonin gene-related peptide immunoreactive synaptic contacts in the thalamus of the rat

Recent studies have shown a prominent calcitonin gene-related peptide immunoreactive (CGRP-ir) pathway extending from the external medial and external lateral para-brachial nuclei to the area surrounding and including the gustatory nuclei in the thalamus, and the cortex and amygdala. The function of the CGRP-ir pathway is not completely understood, but may be involved with the processing of both nociceptive and gustatory information in the thalamus. The purpose of this study was to characterize the nature of the CGRP-ir synaptic contacts in the gustatory nucleus. Electron microscopic examination of CGRP-ir synaptic contacts revealed two classes of CGRP-ir terminals. One class, which was large, formed asymmetric synaptic contacts on dendritic appendages, had many small, round synaptic vesicles, and heavy patches of reaction product which obscured any underlying organelles. Since similar terminals in unstained tissue contained large numbers of dense-cored vesicles, it was concluded that CGRP-ir was contained predominantly in dense-cored vesicles. A second class of CGRP-ir terminals was smaller and made either asymmetric or symmetric synaptic contacts. Both symmetric and asymmetric small terminals contained small, round synaptic vesicles and fewer patches of dense reaction product. Several of the CGRP-ir terminals making symmetric contacts also contained pleomorphic vesicles. There were very few contacts on cell bodies. There were no contacts on other CGRP-ir elements, somal or dendritic, or on axon terminals. None of the CGRP-ir terminal elements were postsynaptic to unlabeled terminals. Axons containing CGRP-ir were primarily unmyelinated, but a few myelinated axons were also seen. © 1993 Wiley-Liss, Inc.     

Distribution of calcitonin gene-related peptide immunoreactivity in relation to the rat central somatosensory projection

The distribution of the neuropeptide calcitonin gene-related peptide (CGRP) was studied in relation to the known subcortical somatosensory pathways and contiguous systems in the central nervous system (CNS) of rats by using peroxidase histochemical methods in order to relate zones of immunoreactivity (IR) to cytoarchitecture. CGRP is the most ubiquitous peptide found to date in sensory ganglion cells: principally small and medium-size neurons emitting thin axons inferred to be largely nociceptive in function on the basis of the peripheral distribution of their terminals. Its apparent absence in sympathetic axons provides an especially useful sensory marker. The distribution of CGRP-IR axons displays remarkable selectivity at each level of the CNS. The trigeminal root distributes axons primarily to the pericornual layers (laminae I and II) of spinal V nucleus caudalis and to subnucleus oralis, evading the subnucleus interpolaris and contributing only few axons to principal V. Although there are only a few CGRP-IR somata at each level, heavily labeled axon trajectories can be traced to the nuclei of the solitary tract, the parabrachial nuclei, several sectors of the caudal medial thalamus, and the central nucleus of the amygdala. A sector of labeled neuron somata lies contiguous to each of these axon terminal zones, the largest of which is a thalamic nucleus containing cells of distinctive dendritic architecture extending from the periaqueductal gray across the posterior group nuclei to the peripeduncular nucleus, forming a linear array at the mesodiencephalic junction. The relation of CGRP-IR axonal distribution to spinothalamic, visceral, and gustatory systems is discussed in the context of a specialized "chemosensory" component of the thin-fiber somatosensory system.     

Thalamic connections of three representations of the body surface in somatosensory cortex of gray squirrels

The anatomical tracer, wheat germ agglutinin, was used to determine the connections of electrophysiologically identified locations in three architectonically distinct representations of the body surface in the somatosensory cortex of gray squirrels. Injections in the first somatosensory area, S-I, revealed reciprocal connections with the ventroposterior nucleus (VP), a portion of the thalamus just dorsomedial to VP, the posterior medial nucleus, Pom, and sometimes the ventroposterior inferior nucleus (VPI). As expected, injections in the representation of the face in S-I resulted in label in ventroposterior medial (VPM), the medial subnucleus of VP, whereas injections in the representation of the body labeled ventroposterior lateral (VPL), the lateral subnucleus of VP. Furthermore, there was evidence from connections that the caudal face and head are represented dorsolaterally in VPM, and the forelimb is represented centrally and medially in VPL. The results also support the conclusion that a representation paralleling that in VP exists in Pom, so that the ventrolateral part of Pom represents the face and the dorsomedial part of Pom is devoted to the body. Because connections with VPI were not consistently revealed, the possibility exists that only some parts or functional modules of S-I are interconnected with VPI. Two separate small representations of the body surface adjoin the caudoventral border of S-I. Both resemble the second somatosensory area, S-II, enough to be identified as S-II in the absence of evidence for the other. We term the more dorsal of the two fields S-II because it was previously defined as S-II in squirrels (Nelson et al., '79), and because it more closely resembles the S-II identified in most other mammals. We refer to the other field as the parietal ventral area, PV (Krubitzer et al, '86). Injections in S-II revealed reciprocal connections with VP, Pom, and a thalamic region lateral and caudal to Pom and dorsal to VP, the posterior lateral nucleus, Pol. Whereas major interconnections between S-II and VPI have been reported for cats, raccoons, and monkeys, no such interconnections were found for S-II in squirrels. The parietal ventral area, PV, was found to have prominent reciprocal interconnections with VP, VPI, and the internal (magnocellular) division of the medial geniculate complex (MGi). The pattern of connections conforms to the established somatotopic organization of VP and suggests a crude parallel somatotopic organization in VPI. Less prominent interconnections were with Pol.(ABSTRACT TRUNCATED AT 400 WORDS)     

Thalamic projections to retrosplenial cortex in the rat

The topographic relationships between anterior thalamic neurons and their terminal projection fields in the retrosplenial cortex of the rat were characterized by experiments with the fluorescent dye retrograde labeling technique. The results demonstrate that the anterodorsal (DAD) and anteroventral (AV) nuclei project heavily to retrosplenial granular cortex (Rg) and to a lesser extent to retrosplenial agranular cortex (Rag). In contrast, the anteromedial (AM) and lateral dorsal (LD) nuclei project heavily to Rag and more lightly to Rg. Irrespective of terminal field in Rg or Rag, the neuronal cell bodies in AD and AV are organized topographically so that the neurons in the caudal part of each nucleus project to rostral retrosplenial cortex and the neurons in the rostral portion of each nucleus project to the caudal retrosplenial cortex. Further, the ventromedial AD and AV neurons project to rostral retrosplenial cortex, whereas dorsolateral neurons in both nuclei project to caudal retrosplenial cortex. LD neurons display a different topographic organization. The neurons in the medioventral part of LD project primarily to the rostral retrosplenial cortex, and the neurons in lateral LD project to the caudal retrosplenial cortex. This latter projection to the caudal retrosplenial cortex is also contributed to by neurons residing in the mediodorsal part of caudal LD. The neurons in AM that project to the retrosplenial cortex display less segregation than the AV, AD, or LD neurons. In all experiments, a number of neurons in the dorsal ventro-anterolateral nucleus were labeled by retrosplenial injections. The largest number of cells in this nucleus were labeled after Rag injections, and these were topographically organized such that the neurons projecting to the rostral Rag were located immediately deep to the internal medullary lamina, and the neurons projecting to the caudal Rag were more ventrally located. Very few thalamic neurons have axon collaterals to different areas of the retrosplenial cortex as shown by double labeling experiments. Together, these results demonstrate a highly organized thalamic projection to the retrosplenial cortex.     

Calcitonin gene-related peptide in afferents to the cat's cerebellar cortex: distribution and origin.

In the present study, the distribution and origin of calcitonin gene-related peptide (CGRP) were analyzed in the cat's cerebellum. Following incubation in an antibody generated against rat CGRP and processing with the peroxidase anti-peroxidase (PAP) technique, CGRP immunoreactivity (IR) is found in profiles that have morphological characteristics of both simple and complex mossy fibers. However, all mossy fibers are not CGRP-positive. Further, CGRP-IR mossy fibers have a heterogeneous distribution in the cerebellum. In the vermis, the majority of immunoreactive profiles are in lobules VII, VIII, and the dorsal folia of IX. In anterior vermal lobules, only scattered terminals, located primarily at the apex and along the shoulder of the folia, are present. Laterally, CGRP-IR mossy fibers are located in the paramedian lobule, paraflocculus, and crus II. No CGRP fibers or varicosities are observed in any of the cerebellar nuclei. However, CGRP-positive cell bodies are scattered throughout the nuclear neuropil. A double label technique revealed that CGRP-IR mossy fibers arise from neurons located in the lateral reticular nucleus, external cuneate nucleus, inferior vestibular nucleus, and basilar pons. The present findings, taken together with previous data, indicate that cerebellar afferents are chemically heterogeneous. The findings of the present study suggest that precerebellar nuclei that give rise to the mossy fibers that contain CGRP have the potential for playing a complex role in modulating circuitry in the cerebellar cortex of the cat.     

A subset of thalamocortical projections to the retrosplenial cortex possesses two vesicular glutamate transporter isoforms,VGluT1 and VGluT2, in axon terminals and somata

Vesicular glutamate transporter isoforms, VGluT1–VGluT3, accumulate glutamate into synaptic vesicles and are considered to be important molecules in glutamatergic transmission. Among them, VGluT2 mRNA is expressed predominantly throughout the dorsal thalamus, whereas VGluT1 mRNA is expressed in a few thalamic nuclei. In the thalamic nuclei that project to the retrosplenial cortex (RSC), VGluT1 mRNA is expressed strongly in the anterodorsal thalamic nucleus (AD), is expressed moderately in the anteroventral and laterodorsal thalamic nuclei, and is not expressed in the anteromedial thalamic nucleus. Thus, it has been strongly suggested that a subset of thalamocortical projections to RSC possesses both VGluT1 and VGluT2. In this study, double‐labeled neuronal somata showing both VGluT1 and VGluT2 immunolabelings were found exclusively in the ventral region of AD (vAD). Many double‐labeled axon terminals were also found in two major targets of vAD, the rostral part of the reticular thalamic nucleus and layers Ia and III–IV of the retrosplenial granular b cortex (RSGb). Some were also found in layer Ia of the retrosplenial granular a cortex (RSGa). These axon terminals contain significant amounts of both VGluTs. Because the subset of thalamocortical projections to RSC has a unique molecular basis in the glutamatergic transmission system, it might play an important role in the higher cognitive functions processed in the RSC. Furthermore, double‐labeled axon terminals of a different type were distributed in RSGb and RSGa. Because they are small and the immunoreactivity of VGluT2 is significantly weaker than that of VGluT1, they seemed to be a subset of corticocortical terminals. J. Comp. Neurol. 522:2089–2106, 2014. © 2013 Wiley Periodicals, Inc.     

Identification of thalamic neurons with vasoactive intestinal polypeptide-like immunoreactivity in the rat

Cell bodies with vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) were found in the thalamus of the rat. They were distributed throughout the ventrolateral nucleus (VL) and in the whole extent of the thalamic reticular nucleus (R) except for its most rostral part. On the basis of soma diameters, VIP-LI cells in the VL and R were assumed to be projection neurons.     

Regulation of dopamine function in the prefrontal cortex of the rat by the thalamic mediodorsal nucleus

Dopamine (DA) utilisation has been assessed in the medial bank of the prefrontal cortex (FCx) and the agranular insular cortex (AgCx) of the rat in response to unilateral manipulations of the thalamic mediodorsal nucleus (MD). The ratios of 3,4-dihydroxyphenylacetic acid (DOPAC):DA and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid, HVA):DA are used as indices of DA utilisation and were shown to increase in the ipsilateral FCx following electrical stimulation of lateral MD. A similar response was observed 1 hr after an infusion of the excitotoxin sodium ibotenate into lateral MD, although in this case the increase in DA utilisation in FCx was bilateral. Longer periods of recovery after ibotenate treatment (2 day and 1 week) produced DA utilisation ratios that had returned to near control values and by 1 week a significant decrease was detected in HVA:DA of the contralateral FCx. All treatments had little effect on DA utilisation in AgCx, although there was a tendency towards enhanced ratios after electrical stimulation and short-term ibotenate injection. These findings suggest that stimulation of MD neurones may tend to activate the DA system in their convergent terminal regions of cortex. It is argued that these influences result from interactions at the level of the DA terminal rather than at the cell bodies of mesocortical DA neurones.     

实验性大鼠大脑皮层梗死后继发丘脑损害与DNA氧化损伤

目的观察大鼠大脑皮层梗死后丘脑腹后外侧核(ventroposterior nucleus of the thalamus,VPN)的继发性损害是否有DNA氧化损伤,并研究抗氧化剂依布硒啉(ebselen,EB)对这种远隔部位损伤是否具有改善作用。方法采用易卒中型肾血管性高血压大鼠(stroke-prone renovascular hypertensive rats,RHRSP),建立大脑中动脉皮层支闭塞(middle cerebral artery occlusion,MCAO)模型后分为:①假手术组,②模型组,③溶剂组,④抗氧化剂EB10mg.kg-1组,⑤抗氧化剂EB30mg.kg-1组,每组5只大鼠。2周后行肢体运动神经功能评估并取VPN后行尼氏染色,免疫组化检测VPN的8-羟基-2-脱氧马苷(8-hydroxy-2-deoxyguanosine,8-ohdG)表达。结果EB10mg.kg-1组和EB30mg.kg-1组神经功能评分优于假手术组(1.80±0.56,1.72±0.48vs2.28±0.33,P<0.05)。尼氏染色可见假手术组同侧VPN细胞形态规整。而梗死同侧VPN神经细胞出现细胞体积变小,胞核固缩,尼氏体退变为萎缩的深色细胞。EB30mg.kg-1组尼氏染色观察到改善作用。溶剂组同侧VPN的8-ohdG阳性细胞数目(0.1mm2)显著增加(146.8±12.1vs108.4±19.2,P<0.05);与溶剂组相比,EB10mg.kg-1组和EB30mg.kg-1组阳性细胞数目显著下降(123.6±14.7,123.4±17.4vs146.8±12.1,P<0.05)。结论实验性大脑皮层梗死后2周,同侧VPN存在DNA氧化性损伤。抗氧化剂EB对VPN的DNA氧化损伤有抑制作用,并可改善神经功能。     

Ascending general visceral sensory pathways from the brainstem to the forebrain in a cichlid fish,Oreochromis (Tilapia) niloticus

Fiber connections of the general visceral sensory centers in the brainstem were studied with tract‐tracing methods in a percomorph teleost, tilapia Oreochromis niloticus. General visceral afferents of the vagal nerve from abdominal viscera terminated bilaterally in the commissural nucleus of Cajal (NCC) and area postrema (AP). The NCC and AP projected bilaterally to the secondary general visceral nucleus (SVN), four diencephalic nuclei (the preglomerular general visceral nucleus [pVN], nucleus of the lateral recess, posterior thalamic nucleus, and lateral tuberal area), preoptic area, and ventral telencephalon (supracommissural, dorsal, and ventral parts) in addition to the glossopharyngeal and vagal lobes and medullary reticular formation. Injections to the SVN resulted in labeled terminals in the forebrain structures that receive fibers from the primary centers and additionally in the diffuse nucleus of the inferior lobe, lateral torus, and inferior subdivision of lateral torus. The present study suggests that the ascending general visceral projections arising from the brainstem centers in teleosts are quite similar to those in mammals and birds. Descending pathways were also notable. In addition to descending projections from the SVN and medullary structures to the primary centers, long descending pathways to the SVN, NCC, and AP were found to originate from the pVN, nucleus of the lateral recess, posterior thalamic nucleus, and preoptic area. The SVN was found to receive fibers from the ventral telencephalon as well. Therefore, the present study indicates that most of the general visceral structures in the forebrain are reciprocally connected with the brainstem centers. J. Comp. Neurol. 518:3570–3603, 2010. © 2010 Wiley‐Liss, Inc.     

Calcitonin gene-related peptide and corneal innervation: a developmental study in the rat.

The development of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nerves was studied in neonatal and adult rat corneas stained immunohistochemically according to an avidin biotin peroxidase procedure. At birth, rat corneas already contained dense plexuses of CGRP-LI nerve fibers. Most of the nerves entered the cornea in 12-15 prominent stromal nerve bundles located at regular intervals around the circumference of the cornea. Fibers in these bundles entered the epithelium approximately midway between the limbus and the center of the cornea and supplied extensive central and pericentral areas of the tissue. In addition, smaller numbers of axons entered the cornea individually and in small fascicles located in between the larger bundles and supplied mainly peripheral territory. In the epithelium, the CGRP-LI nerves formed a complex, highly anastomotic meshwork that ramified uniformly throughout central and peripheral areas of the tissues. Fibers in the plexus gave origin to numerous short, stout terminal axons that extended into the adjacent epithelium in all directions with no preferred orientation. During the first week of neonatal life, several changes in CGRP-LI innervation occurred: 1) the innervation density of the central and pericentral cornea increased relative to the peripheral cornea; 2) intraepithelial axons became progressively longer, increased in branching complexity, and oriented preferentially towards the center of the cornea; and 3) a dense innervation of the corneoscleral limbus and, in particular, the branches of the marginal artery, developed. Midway through the second week of life, immature versions of corneal epithelial "leashes," the dominant feature of the adult corneal innervation, were first observed. Over the next 10 days, the leash formations in the central and pericentral cornea gradually became more complex and gave rise to greater numbers of terminal axons, compared to developing leashes in the peripheral cornea. The mature pattern of corneal CGRP-LI innervation was reached on day 21 and remained constant (except for compensatory growth-related elongation of axons) for at least the first 6 months of life. Transection of the ophthalmomaxillary nerve or neonatal administration of the sensory neurotoxin capsaicin resulted in the total loss of CGRP-LI staining from the cornea. In contrast, removal of the superior cervical ganglion had no effect on corneal CGRP-LI staining. The extraordinary density and complexity of the CGRP-LI innervation of the rat cornea demonstrated at all stages of development in this study suggests that these nerves may play important roles in corneal sensory, reflex, and trophic functions.     

Immunoelectron microscopic study of glutamate inputs from the retrosplenial granular cortex to identified thalamocortical projection neurons in the anterior thalamus of the rat

We have carried out an ultrastructural study to determine the characteristics and distribution of glutamate-containing constituents of the anterodorsal (AD) and anteroventral (AV) thalamic nuclei in adult rats. We used a polyclonal antibody to glutamate and a postembedding immunogold detection method in animals in which the neurons of AD/AV projecting to the cortex had been retrogradely labelled and the terminals of corticothalamic afferents anterogradely labelled by injection of cholera toxin-horseradish peroxidase (HRP) into the retrosplenial granular cortex. The heaviest immunogold labelling was over axon terminals 0.42 to 2.2 microm in diameter containing round synaptic vesicles and establishing Gray type 1 (asymmetric) synaptic contact (type 1 terminals) on HRP-labelled or non-labelled dendrites. Mean gold particle densities over such terminals were 3-4 times higher than the densities over the dendrites to which they were presynaptic and 5-6 times higher than over terminals establishing Gray type 2 (symmetric) synaptic contacts (type 2 terminals). Gold particle densities over neuronal cell bodies and dendrites and over a subpopulation of myelinated axons were intermediate between the densities over type 1 and type 2 terminals. In adjacent serial sections immunoreacted for gamma aminobutyric acid, type 2 terminals were heavily immunolabelled whereas type 1 terminals and other profiles with moderate gold particle densities after glutamate immunoreaction displayed very low labelling. A subpopulation of small type 1 axon terminals (up to 1 microm diameter) contained HRP reaction product identifying them as cortical in origin; they contacted small dendritic profiles (most <1 microm diameter) many of which also contained HRP reaction product. We conclude that terminals of the corticothalamic projection from retrosplenial granular cortex to AD/AV are glutamatergic and innervate predominantly distal dendrites of thalamocortical projection neurons.     

Ultrastructure of cholinergic synaptic terminals in the thalamic anteroventral,ventroposterior, and dorsal lateral geniculate nuclei of the rat

The principal relay nuclei of the thalamus receive their cholinergic innervation from two midbrain cholinergic groups: the pedunculopontine tegmental nucleus and the laterodorsal tegmental nucleus. The different thalamic nuclei exhibit populations of cholinergic axons which vary in density and morphology when examined at the light microscopic level. However, the ultrastructure of the cholinergic terminals in different thalamic nuclei has not been described. This study was undertaken to confirm that synaptic contacts are formed by cholinergic axons in several principal thalamic relay nuclei, to describe their ultrastructural morphology, and to identify the types of postsynaptic elements contacted by cholinergic synaptic terminals. The thalamic nuclei examined in this study are the dorsal lateral geniculate nucleus, ventroposteromedial nucleus, ventroposterolateral nucleus, and anteroventral nucleus. Our results confirm that cholinergic axons form synaptic terminals in these thalamic nuclei. Cholinergic synaptic terminals contact structures outside the characteristic synaptic glomeruli, are never postsynaptic, and have morphologies and postsynaptic targets which differ among the thalamic nuclei. In the ventroposterior nuclei, cholinergic terminals form asymmetric synaptic contacts onto larger dendrites in the extraglomerular neuropil. In the anteroventral nucleus, cholinergic terminals form both symmetric and asymmetric synaptic contacts onto dendrites and somata. Cholinergic terminals in the anteroventral nucleus are larger than those in other nuclei. In the dorsal lateral geniculate nucleus, cholinergic terminals contact both somata and dendrites in the extraglomerular neuropil, but the synaptic contacts in this nucleus are symmetric in morphology.     

Calcitonin gene-related peptide-like immunoreactivity, in botulinum toxin-paralysed rat muscles

Changes in calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) at the motor endplates of botulinum toxin-paralysed rat muscles were investigated using immunohistochemistry. One day following toxin injection, a dramatic increase in CGRP-LI was detected at the motor endplates and within preterminal axons of the soleus and gastrocnemius muscles. The upregulation of CGRP-LI persisted throughout the period during which muscle fibres were paralysed and new neuromuscular junctions were being formed by the growing sprouts. Decline of CGRP-LI at the motor endplates coincided with clinical recovery. Both up- and down-regulation of CGRP-LI took place earlier in the soleus than in the gastrocnemius muscle. Up-regulation of CGRP-LI was also detected in a subpopulation of motor axons in the sciatic nerves and in the spinal motor neurons innervating the paralysed muscles. These results indicate that levels of CGRP are regulated, at least partly, by changes in the target innervation. They also suggest an important role for CGRP in the regenerative processes following muscle paralysis.