@article{15404, abstract = {We used diverse methods to characterize the role of avian lateral spiriform nucleus (SpL) in basal ganglia motor function. Connectivity analysis showed that SpL receives input from globus pallidus (GP), and the intrapeduncular nucleus (INP) located ventromedial to GP, whose neurons express numerous striatal markers. SpL-projecting GP neurons were large and aspiny, while SpL-projecting INP neurons were medium sized and spiny. Connectivity analysis further showed that SpL receives inputs from subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr), and that the SNr also receives inputs from GP, INP, and STN. Neurochemical analysis showed that SpL neurons express ENK, GAD, and a variety of pallidal neuron markers, and receive GABAergic terminals, some of which also contain DARPP32, consistent with GP pallidal and INP striatal inputs. Connectivity and neurochemical analysis showed that the SpL input to tectum prominently ends on GABAA receptor-enriched tectobulbar neurons. Behavioral studies showed that lesions of SpL impair visuomotor behaviors involving tracking and pecking moving targets. Our results suggest that SpL modulates brainstem-projecting tectobulbar neurons in a manner comparable to the demonstrated influence of GP internus on motor thalamus and of SNr on tectobulbar neurons in mammals. Given published data in amphibians and reptiles, it seems likely the SpL circuit represents a major direct pathway-type circuit by which the basal ganglia exerts its motor influence in nonmammalian tetrapods. The present studies also show that avian striatum is divided into three spatially segregated territories with differing connectivity, a medial striato-nigral territory, a dorsolateral striato-GP territory, and the ventrolateral INP motor territory.}, author = {Reiner, Anton and Medina, Loreta and Abellan, Antonio and Deng, Yunping and Toledo, Claudio A.B. and Luksch, Harald and Vega Zuniga, Tomas A and Riley, Nell B. and Hodos, William and Karten, Harvey J.}, issn = {1096-9861}, journal = {Journal of Comparative Neurology}, number = {5}, publisher = {Wiley}, title = {{Neurochemistry and circuit organization of the lateral spiriform nucleus of birds: A uniquely nonmammalian direct pathway component of the basal ganglia}}, doi = {10.1002/cne.25620}, volume = {532}, year = {2024}, } @article{9955, abstract = {Neurons can change their classical neurotransmitters during ontogeny, sometimes going through stages of dual release. Here, we explored the development of the neurotransmitter identity of neurons of the avian nucleus isthmi parvocellularis (Ipc), whose axon terminals are retinotopically arranged in the optic tectum (TeO) and exert a focal gating effect upon the ascending transmission of retinal inputs. Although cholinergic and glutamatergic markers are both found in Ipc neurons and terminals of adult pigeons and chicks, the mRNA expression of the vesicular acetylcholine transporter, VAChT, is weak or absent. To explore how the Ipc neurotransmitter identity is established during ontogeny, we analyzed the expression of mRNAs coding for cholinergic (ChAT, VAChT, and CHT) and glutamatergic (VGluT2 and VGluT3) markers in chick embryos at different developmental stages. We found that between E12 and E18, Ipc neurons expressed all cholinergic mRNAs and also VGluT2 mRNA; however, from E16 through posthatch stages, VAChT mRNA expression was specifically diminished. Our ex vivo deposits of tracer crystals and intracellular filling experiments revealed that Ipc axons exhibit a mature paintbrush morphology late in development, experiencing marked morphological transformations during the period of presumptive dual vesicular transmitter release. Additionally, although ChAT protein immunoassays increasingly label the growing Ipc axon, this labeling was consistently restricted to sparse portions of the terminal branches. Combined, these results suggest that the synthesis of glutamate and acetylcholine, and their vesicular release, is complexly linked to the developmental processes of branching, growing and remodeling of these unique axons.}, author = {Reyes‐Pinto, Rosana and Ferrán, José L. and Vega Zuniga, Tomas A and González‐Cabrera, Cristian and Luksch, Harald and Mpodozis, Jorge and Puelles, Luis and Marín, Gonzalo J.}, issn = {1096-9861}, journal = {Journal of Comparative Neurology}, number = {2}, pages = {553--573}, publisher = {Wiley}, title = {{Change in the neurochemical signature and morphological development of the parvocellular isthmic projection to the avian tectum}}, doi = {10.1002/cne.25229}, volume = {530}, year = {2022}, } @article{7148, abstract = {In the cerebellum, GluD2 is exclusively expressed in Purkinje cells, where it regulates synapse formation and regeneration, synaptic plasticity, and motor learning. Delayed cognitive development in humans with GluD2 gene mutations suggests extracerebellar functions of GluD2. However, extracerebellar expression of GluD2 and its relationship with that of GluD1 are poorly understood. GluD2 mRNA and protein were widely detected, with relatively high levels observed in the olfactory glomerular layer, medial prefrontal cortex, cingulate cortex, retrosplenial granular cortex, olfactory tubercle, subiculum, striatum, lateral septum, anterodorsal thalamic nucleus, and arcuate hypothalamic nucleus. These regions were also enriched for GluD1, and many individual neurons coexpressed the two GluDs. In the retrosplenial granular cortex, GluD1 and GluD2 were selectively expressed at PSD‐95‐expressing glutamatergic synapses, and their coexpression on the same synapses was shown by SDS‐digested freeze‐fracture replica labeling. Biochemically, GluD1 and GluD2 formed coimmunoprecipitable complex formation in HEK293T cells and in the cerebral cortex and hippocampus. We further estimated the relative protein amount by quantitative immunoblotting using GluA2/GluD2 and GluA2/GluD1 chimeric proteins as standards for titration of GluD1 and GluD2 antibodies. Intriguingly, the relative amount of GluD2 was almost comparable to that of GluD1 in the postsynaptic density fraction prepared from the cerebral cortex and hippocampus. In contrast, GluD2 was overwhelmingly predominant in the cerebellum. Thus, we have determined the relative extracerebellar expression of GluD1 and GluD2 at regional, neuronal, and synaptic levels. These data provide a molecular–anatomical basis for possible competitive and cooperative interactions of GluD family members at synapses in various brain regions.}, author = {Nakamoto, Chihiro and Konno, Kohtarou and Miyazaki, Taisuke and Nakatsukasa, Ena and Natsume, Rie and Abe, Manabu and Kawamura, Meiko and Fukazawa, Yugo and Shigemoto, Ryuichi and Yamasaki, Miwako and Sakimura, Kenji and Watanabe, Masahiko}, issn = {1096-9861}, journal = {Journal of Comparative Neurology}, number = {6}, pages = {1003--1027}, publisher = {Wiley}, title = {{Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain}}, doi = {10.1002/cne.24792}, volume = {528}, year = {2020}, } @article{2618, abstract = {The unipolar brush cell (UBC) is a type of glutamatergic interneuron in the granular layer of the cerebellum. The UBC brush and a single mossy fiber (MF) terminal contact each other within a cerebellar glomerulus, forming a giant synapse. Many UBCs receive input from extrinsic MFs, whereas others are innervated by intrinsic mossy terminals formed by the axons of other UBCs. In all mammalian species so far examined, the vestibulocerebellum is enriched of UBCs that are strongly immunoreactive for the calcium binding protein calretinin (CR) in both the somatodendritic and axonal compartment. UBCs have postsynaptic ionotropic glutamate receptors and extrasynaptic metabotropic glutamate receptors that immunocytochemically highlight their somatodendritic compartment and brush, respectively. In this study on the mouse cerebellum, we present evidence that immunoreactivities to CR and mGluR1α define two distinct UBC subsets with partly overlapping distributions in lobule X (the nodulus). In sections double-labeled for CR and mGluR1α, the patterns of distributions of CR+/mGluR1α- UBCs and CR-/mGluR1α+ UBCs differed along the mediolateral and dorsoventral axes of the folium. Moreover, mGluR1α+ UBCs outnumbered CR+ UBCs. Both UBC subsets were mGluR2/3, GluR2/3, and NMDAR1 immunoreactive. The different distribution patterns of the two UBC subsets within lobule X suggest that expression of CR or mGluR1α by UBCs may be afferent-specific and related to the terminal fields of different vestibular MF afferents.}, author = {Nunzi, Maria and Shigemoto, Ryuichi and Mugnaini, Enrico}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {2}, pages = {189 -- 199}, publisher = {Wiley-Blackwell}, title = {{Differential expression of calretinin and metabotropic glutamate receptor mGluR1α defines subsets of unipolar brush cells in mouse cerebellum}}, doi = {10.1002/cne.10344}, volume = {451}, year = {2002}, } @article{2604, abstract = {Cutaneous antidromic vasodilatation and plasma extravasation, two phenomena that occur in neurogenic inflammation, are partially blocked by substance P (SP) receptor antagonists and are known to be mediated in part by mast cell-released substances, such as histamine, serotonin, and nitric oxide. In an attempt to provide a morphological substrate for the above phenomena, we applied light and electron microscopic immunocytochemistry to investigate the pattern of SP innervation of blood vessels and its relationship to mast cells in the skin of the rat lower lip. Furthermore, we examined the distribution of SP (neurokinin-1) receptors and their relationship to SP-immunoreactive (IR) fibers. Our results confirmed that SP-IR fibers are found in cutaneous nerves and that terminal branches are observed around blood vessels and penetrating the epidermis. SP-IR fibers also innervated hair follicles and sebaceous glands. At the ultrastructural level, SP-IR varicosities were observed adjacent to arterioles, capillaries, venules, and mast cells. The varicosities possessed both dense core vesicles and agranular synaptic vesicles. We quantified the distance between SP-IR varicosities and blood vessel endothelial cells. SP-IR terminals were located within 0.23-5.99 μm from the endothelial cell layer in 82.7% of arterioles, in 90.2% of capillaries, and in 86.9% of venules. Although there was a trend for SP-IR fibers to be located closer to the endothelium of venules, this difference was not significant. Neurokinin-1 receptor (NK-1r) immunoreactivity was most abundant in the upper dermis and was associated with the wall of blood vessels. NK-1r were located in equal amounts on the walls of arterioles, capillaries, and venules that were innervated by SP-IR fibers. The present results favor the concept of a participation of SP in cutaneous neurogenic vasodilatation and plasma extravasation both by an action on blood vessels after binding to the NK-1r and by causing the release of substances from mast cells after diffusion through the connective tissue.}, author = {Ruocco, Isabella and Cuello, Augusto and Shigemoto, Ryuichi and Ribeiro Da Silva, Alfredo}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {4}, pages = {466 -- 480}, publisher = {Wiley-Blackwell}, title = {{Light and electron microscopic study of the distribution of substance P-immunoreactive fibers and neurokinin-1 receptors in the skin of the rat lower lip}}, doi = {10.1002/cne.1114}, volume = {432}, year = {2001}, } @article{2599, abstract = {The synaptic relationship between substance P (SP) and its receptor, i.e., neurokinin-1 receptor (NK1R), was examined in the striatum of the rat by confocal laser-scanning microscopy and electron microscopy. For confocal laser-scanning microscopy, triple-immunofluorescence histochemistry was performed to label NK1R, SP, and vesicular acetylcholine transporter (a specific marker for cholinergic neurons). In electron microscopic double- immunolabeling study, immunoreactivity for NK1R was detected with the silver- intensified gold method, while immunoreactivity for SP was detected with peroxidase immunohistochemistry. Simultaneous immunolabeling of NK1R and SP revealed significant mismatch at the synaptic level: although some SP- immunopositive axon terminals were in synaptic contact with NK1R- immunopositive sites of plasma membrane, NK1R-immunoreactivity was observed at both synaptic and non-synaptic sites of plasma membrane. Thus, SP released from the sites remote from NK1Rs might diffuse in the extracellular fluid to act, as a paracrine neurotransmitter, on NK1Rs distant from its releasing site. SP neurotransmission in the striatum might occur not only synaptically but also extrasynaptically. The SP-NK1R system might constitute an association system within the striatum.}, author = {Li, Jin and Wang, Dan and Kaneko, Takeshi and Shigemoto, Ryuichi and Nomura, Sakashi and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {2}, pages = {156 -- 163}, publisher = {Wiley-Blackwell}, title = {{Relationship between neurokinin-1 receptor and substance P in the striatum: Light and electron microscopic immunohistochemical study in the rat}}, doi = {10.1002/(SICI)1096-9861(20000306)418:2<156::AID-CNE3>3.0.CO;2-Z}, volume = {418}, year = {2000}, } @article{2596, abstract = {A γ-aminobutyric acid (GABA)(B) receptor (named GABA(B)R1) has been recently cloned in the rat and human brain and two variants generated by alternative RNA splicing were identified. In the present study, we addressed the question as to whether these variants contribute to the diversity of GABA(B) receptor-mediated physiological responses and constitute real receptor subtypes with distinct functions. To this aim, we have mapped the GABA(B)R1 (R1a) and GABA(B)R1b (R1b) transcript distribution in the rat brain using in situ hybridization. We have compared the mRNA distribution with the distribution of [ 3H]CGP54626-labeled binding GABA(B)R1 receptor sites as assessed in adjacent cryosections by quantitative autoradiography. We found that GABA(B) receptor transcripts and binding sites are expressed in the brain in almost all neuronal cell populations. Expression in glial cells, if any, is marginal. We observed a good parallelism between GABA(B)R1 mRNA transcripts and binding sites in broad neuroanatomical entities with highest densities in hippocampus, thalamic nuclei, and cerebellum. By contrast, R1a and R1b transcripts exhibit marked differences in their regional and cellular distribution pattern. A typical example is the cerebellum with an almost exclusive expression of R1b in the Purkinje cells and of R1a in the granule, stellate, and basket cells. Data pointing at a pre- versus postsynaptic localization for R1a and R1b, respectively, at some neuronal sites are presented. }, author = {Bischoff, Serge and Leonhard, Sabine and Reymann, Nicole and Schuler, Valérie and Shigemoto, Ryuichi and Kaupmann, Klemens and Bettler, Bernhard}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {1}, pages = {1 -- 16}, publisher = {Wiley-Blackwell}, title = {{Spatial distribution of GABA(B)R1 receptor mRNA and binding sites in the rat brain^}}, doi = {10.1002/(SICI)1096-9861(19990913)412:1<1::AID-CNE1>3.0.CO;2-D}, volume = {412}, year = {1999}, } @article{2584, abstract = {The distributions of two alternative splicing variants of metabotropic glutamate receptor mGluR7, mGluR7a and mGluR7b, were examined immunohistochemically in the rat and mouse by using variant-specific antibodies raised against C-terminal portions of rat mGluR7a and human mGluR7b. Many regions throughout the central nervous system (CNS) showed mGluR7-like immunoreactivities (LI). The distribution patterns of mGluR7-LI in the rat were substantially the same as those in the mouse, although some species differences were observed in a few regions. Intense mGluR7a-LI was seen in the main and accessory olfactory bulbs, anterior olfactory nucleus, islands of Calleja, superficial layers of the olfactory tubercle, piriform cortex and entorhinal cortex, periamygdaloid cortex, amygdalohippocampal area, hippocampus, layer I of the neocortical regions, globus pallidus, superficial layers of the superior colliculus, locus coeruleus, and superficial layers of the medullary and spinal dorsal horns. The distribution of mGluR7b was more restricted. It was intense in the islands of Calleja, substantia innominata, hippocampus, ventral pallidum, and globus pallidus. The medial habenular nucleus also showed intense mGluR7a-LI in the rat but not in the mouse. For both mGluR7a- and mGluR7b-LI, localization in the active zones of presynaptic axon terminals was confirmed electron microscopically at synapses of both the asymmetrical and symmetrical types. It is noteworthy that mGluR7a-LI is seen preferentially in relay nuclei of the sensory pathways and that both mGluR7a- and mGluR7b-LI are observed not only in presumed glutamatergic axon terminals, but also in non-glutamatergic axon terminals including presumed inhibitory ones. Thus, mGluR7 may play roles not only as an autoreceptor in glutamatergic axon terminals, but also as a presynaptic heteroreceptor in non-glutamatergic axon terminals in various CNS regions.}, author = {Kinoshita, Ayae and Shigemoto, Ryuichi and Ohishi, Hitoshi and Van Der Putten, Herman and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {3}, pages = {332 -- 352}, publisher = {Wiley-Blackwell}, title = {{Immunohistochemical localization of metabotropic glutamate receptors, mGluR7a and mGluR7b, in the central nervous system of the adult rat and mouse: A light and electron microscopic study}}, doi = {10.1002/(SICI)1096-9861(19980413)393:3<332::AID-CNE6>3.0.CO;2-2}, volume = {393}, year = {1998}, } @article{2585, abstract = {Localization of metabetropic glutamate receptor subtypes, mGluR1, mGluRlu, mGluR2/3, mGluR4a, mGluR5, mGluR7a, mGluR7b, and mGluR8, was examined in some of the target areas of projection fibers from the main and accessory olfactory bulbs (MOB and AOB) by using subtype-specific antibodies. The superficial layer of the olfactory tubercle and layer Ia of the pitiform cortex, the target areas of MOB, showed marked mGluR1-, mGluR5-, mGluR7a-, and mGluR8-like immunoreactivities (-LI), and rather weak mGluR2/3-LI. The periamygdaloid cortical region including the target areas of both MOB and AOB showed intense mGluR2/3-LI as well as marked mGluRl-, mGluR5-, mGluR7a-, and mGluRS-LI. No significant mGluR1a-, mGluR4a-, or mGluR7b-LI was seen in these regions. After transection of the lateral olfactory tract, mGluR2/3-, mGluR7a-, and mGluR8-LI were reduced markedly in the target regions on the side ipsilateral to the transection; no significant changes were detected in mGluR1- or mGIuR5-LI. Double labeling experiments indicated light and electron microscopically colocalization of mGluR7a- and mGluRS-LI in axon terminals on dendritic shafts of presumed interneurons in the superficial layer of the olfactory tubercle and layer Ia of the piriform cortex. Electron microscopically mGluR2/3-LI was seen in preterminal and terminal portions of axons, whereas mGluR7a- and mGluRS-LI were associated with presynaptic membrane specialization. Immunolabeled axon terminals were filled with round synaptic vesicles and constituted asymmetric synapses with dendritic profiles. The results suggest that glutamate release from axon terminals of projection fibers from MOB and AOB is regulated presynaptically and differentially through mGluR2/3, mGluR7a, and/or mGluRS.}, author = {Wada, Eiki and Shigemoto, Ryuichi and Kinoshita, Ayae and Ohishi, Hitoshi and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {4}, pages = {493 -- 504}, publisher = {Wiley-Blackwell}, title = {{Metabotropic glutamate receptor subtypes in axon terminals of projection fibers from the main and accessory olfactory bulbs: A light and electron microscopic immunohistochemical study in the rat}}, doi = {10.1002/(SICI)1096-9861(19980420)393:4<493::AID-CNE8>3.0.CO;2-W}, volume = {393}, year = {1998}, } @article{2589, abstract = {Immunoreactivity for the substance P receptor (NK1 receptor) has been investigated by light and electron microscopy in the dorsal vagal complexes of adult rats and cats. The general pattern of NK1 immunoreactivity was similar for both rat and cat. Numerous NK1-immunoreactive neurons were present in the area postrema, the nucleus of the solitary tract, and the dorsal motor nucleus of the vagus nerve. The density of labelled neurons differed between the subnuclei of the nucleus of the solitary tract. Overall, the efferent neurons of the dorsal motor nucleus of the vagus nerve highly expressed NK1 when compared to neurons in the nucleus of the solitary tract. The results are discussed with reference to the viscerotopic organisation of the dorsal vagal complex. Ultrastructural analysis demonstrated that NK1 immunoreactivity was present only at the membrane surface of somatic and dendritic profiles of neurons. No labelling was found in axon terminals, axons, or glial processes. NK1 immunoreactivity, as revealed by a preembedding immunogold technique in serial ultrathin sections; was preferentially located at nonsynaptic sites. A semiquantitative study suggested that the density of NK1 receptors is statistically higher at membrane sites free of any contact (synaptic or not) with axon terminals. The subcellular localisation of NK1 immunoreactivity was similar for neurons of both rat and cat. These results suggest that in the dorsal vagal complex, substance P might act on NK1 receptors through a process of volume transmission.}, author = {Baude, Agnès and Shigemoto, Ryuichi}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {2}, pages = {181 -- 196}, publisher = {Wiley-Blackwell}, title = {{Cellular and subcellular distribution of substance P receptor immunoreactivity in the dorsal vagal complex of the rat and cat: A light and electron microscope study}}, doi = {10.1002/(SICI)1096-9861(19981214)402:2<181::AID-CNE4>3.0.CO;2-B}, volume = {402}, year = {1998}, } @article{2493, abstract = {A specific antiserum against substance P receptor (SPR) labels nonprincipal neurons in the cerebral cortex of the rat (T. Kaneko et al. [1994], Neuroscience 60:199-211; Y. Nakaya et al. [1994], J. Comp. Neurol. 347:249-274). In the present study, we aimed to identify the types of SPR- immunoreactive neurons in the hippocampus according to their content of neurochemical markers, which label interneuron populations with distinct termination patterns. Markers for perisomatic inhibitory cells, parvalbumin and cholecystokinin (CCK), colocalized with SPR in pyramidallike basket cells in the dentate gyrus and in large multipolar or bitufted cells within all hippocampal subfields respectively. A dense meshwork of SPR-immunoreactive spiny dendrites in the hilus and stratum lucidum of the CA3 region belonged largely to inhibitory cells terminating in the distal dendritic region of granule cells, as indicated by the somatostatin and neuropeptide Y (NPY) content. In addition, SPR and NPY were colocalized in numerous multipolar interneurons with dendrites branching close to the soma. Twenty-five percent of the SPR-immunoreactive cells overlapped with calretinin-positive neurons in all hippocampal subfields, showing that interneurons specialized to contact other gamma-aminobutyric acid-ergic cells may also contain SPR. On the basis of the known termination pattern of the colocalized markers, we conclude that SPR-positive interneurons are functionally heterogeneous and participate in different inhibitory processes: (1) perisomatic inhibition of principal cells (CCK-containing cells, and parvalbumin-positive cells in the dentate gyrus), (2) feedback dendritic inhibition in the entorhinal termination zone (somatostatin and NPY-containing cells), and (3) innervation of other interneurons (calretinin-containing cells).}, author = {Acsády, László and Katona, István and Gulyás, Attila and Shigemoto, Ryuichi and Freund, Tamás}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {3}, pages = {320 -- 336}, publisher = {Wiley-Blackwell}, title = {{Immunostaining for substance P receptor labels GABAergic cells with distinct termination patterns in the hippocampus}}, doi = {10.1002/(SICI)1096-9861(19970217)378:3<320::AID-CNE2>3.0.CO;2-5}, volume = {378}, year = {1997}, } @article{2576, abstract = {Primary afferent neurons containing substance P (SP) are apparently implicated in the transmission of noxious information from the periphery to the central nervous system, and SP released from primary afferent neurons acts on second-order neurons with the SP receptor (SPR). In the rat, nociceptive information reached the hypothalamus not only through indirect pathways but also directly through trigeminohypothalamic and spinohypothalamic pathways. Thus, in the present study, the distribution pattern of trigeminohypothalamic and spinohypothalamic tract neurons showing SPR-like immunoreactivity (SPR-LI) was examined in the rat by a retrograde tract-tracing method combined with immunofluorescence histochemistry for SPR. A substantial number of trigeminal and spinal neurons with SPR-LI were retrogradely labeled with Fluore-Gold (FG) injected into the hypothalamic regions. These neurons were distributed mainly in lamina I of the medullary and spinal dorsal horns, lateral spinal nucleus, regions around the central canal of the spinal cord, and the lateral aspect of the deep part of the spinal dorsal horn. A number of SPR-LI neurons in the spinal parasympathetic nucleus were labeled with FG injected into the area around the paraventricular hypothalamic nucleus. Some SPR-LI neurons in the lateral spinal nucleus and the lateral aspect of the deep part of the spinal dorsal horn were also labeled with FG injected into the septal region. On the basis of the distribution areas of SPR-LI trigeminal and spinal neurons projecting to the hypothalamic and septal regions, it is likely that these neurons are involved in the transmission of somatic and/or visceral noxious information.}, author = {Li, Jin and Kaneko, Takeshi and Shigemoto, Ryuichi and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {4}, pages = {508 -- 521}, publisher = {Wiley-Blackwell}, title = {{Distribution of trigeminohypothalamic and spinohypothalamic tract neurons displaying substance P receptor-like immunoreactivity in the rat}}, doi = {10.1002/(SICI)1096-9861(19970224)378:4<508::AID-CNE6>3.0.CO;2-6}, volume = {378}, year = {1997}, } @article{2578, abstract = {The distribution of immunoreactivity to the neurokinin3 receptor (NK3R) was examined in segments C7, T11-12, L1-2, and L4-6 of the rat spinal cord. NK3R immunoreactivity was visualized by using two antisera generated against sequences of amino acids contained in the C-terminal region of the NK3R. NK3R-immunoreactive cells were numerous in the substantia gelatinosa of all spinal segments examined as well as the dorsal commissural nucleus of spinal segments L1-2. Isolated, immunoreactive cells were scattered throughout other regions of the spinal cord. The relationship of NK3R-immunoreactivity with neurons was demonstrated by colocalization with microtubule associated protein 2-immunoreactivity in individual cells. Within neurons, NK3R- immunoreactivity was associated predominately with the plasma membrane of cell bodies and dendrites. Within the substantia gelatinosa, 86% of nitric oxide synthase (NOS)-immunoreactive neurons were also NK3R-immunoreactive. Although NOS-immunoreactive neurons were found throughout all other regions of the spinal cord in the segments examined, these were not NK3R- immunoreactive. When preganglionic sympathetic neurons in spinal segments T11-12 and L1-2 were visualized by intraperitoneal injection of Fluorogold, less than 1% of the Fluorogold-labeled neurons were also immunoreactive for NK3R. The large number of NK3R-immunoreactive neurons in the substantia gelatinosa suggests that some effects of tachykinins an somatosensation may be mediated by NK3R.}, author = {Seybold, Virginia and Grković, Ivica and Portbury, Andrea and Ding, Yu and Shigemoto, Ryuichi and Mizuno, Noboru and Furness, John and Southwell, Bridget}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {4}, pages = {439 -- 448}, publisher = {Wiley-Blackwell}, title = {{Relationship of NK3 receptor-immunoreactivity to subpopulations of neurons in rat spinal cord}}, doi = {10.1002/(SICI)1096-9861(19970519)381:4<439::AID-CNE4>3.0.CO;2-3}, volume = {381}, year = {1997}, } @article{2581, abstract = {It is well known that striatonigral neurons produce substance P (SP); however, no SP receptor (SPR) has so far been found in the substantia nigra. On the other hand, a previous study in the rat striatum indicated that SPR was expressed only in cholinergic or somatostatinergic intrinsic neurons (Kaneko et al. [1993] Brain Res. 631:297-303). Thus, it was assumed that SP produced by striatenigral neurons might be released through their intrastriatal axon collaterals to act upon intrinsic neurons in the striatum. To confirm this assumption, the distribution of axon collaterals of striatonigral neurons was examined in the striatum of the rat. The experiments were performed on brain slices by combining retrograde labeling with tetramethylrhodamine-dextran amine, electrophysiological recording, intracellular staining with biocytin, and immunocytochemistry for SPR. The distribution of axons of cholinergic striatal neurons (a group of SP-negative intrinsic striatal neurons) was also examined. It was observed that 16% of varicosities of intrastriatal axon collaterals of striatonigral neurons, as well as 6% of axonal varicosities of cholinergic neurons, were in close apposition to dendrites and cell bodies of SPB-immunoreactive striatal neurons. Since SPR-immunoreactive striatal neurons constituted only 2.7% of the total population of striatal neurons (Kaneko et al. [1993] Brain Res. 631:297-303), it appeared that axonal varicosities of striatonigral neurons were preferentially apposed to SPR-immunoreactive striatal neurons and that the varicosities in close apposition to SPR-immunoreactive neurons were derived more frequently from striatonigral neurons than from cholinergic interneurons. Confocal laser scanning microscopy indicated that axonal varicosities in close apposition to SPR-immunoreactive cells showed synaptophysin immunoreactivity, a marker of synaptic vesicles. In intrastriatal axons of striatonigral neurons, it was further revealed from electron microscopy that axonal varicosities in close apposition to SPR- immunoreactive dendrites, at least a part of them, made synapses of the symmetric type. Striatonigral neurons might release SP preferentially around cholinergic or somatostatinergic intrinsic neurons to regulate them through SP-SPR interactions.}, author = {Lee, Teffy and Kaneko, Takeshi and Shigemoto, Ryuichi and Nomura, Sakashi and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {2}, pages = {250 -- 264}, publisher = {Wiley-Blackwell}, title = {{Collateral projections from striatonigral neurons to substance P receptor-expressing intrinsic neurons in the striatum of the rat}}, doi = {10.1002/(SICI)1096-9861(19971117)388:2<250::AID-CNE5>3.0.CO;2-0}, volume = {388}, year = {1997}, } @article{2564, abstract = {The distribution of the neuromedin K receptor (NK3; NKR) in the central nervous system was investigated in the adult rat by using in situ hybridization and immunohistochemical techniques. The rabbit anti-NKR antibody was raised against a bacterial fusion protein containing a C- terminal portion of NKR and affinity purified with a Sepharose 4B column conjugated to the fusion protein. Immunoblot analysis was performed to test the reactivity and specificity of the antibody. Crude membrane was prepared from cDNA-transfected Chinese hamster ovary (CHO) cells expressing each of the rat NKR, substance P receptor (NK1; SPR), and substance K receptor (NK2; SKR) and from the hypothalamus, cerebral cortex, and cerebellum. Immunoreactive bands were observed specifically in the NKR-CHO cells, hypothalamus, and cerebral cortex but not in the SPR- or SKR-CHO cells, nor in the cerebellum. Molecular weights of the immunoreactive bands ranged from 73 to 89 kDa and from 59 to 83 kDa in the NKR-CHO cells and tissues, respectively. The distribution of NKR-like immunoreactivity coincided with that of NKR mRNA. The expression of NKR was indicated on neuronal cell bodies and dendrites. NKR was found to be expressed intensely or moderately in neurons in the glomerular and granule cell layers of the main olfactory bulb; glomerular and mitral cell layers of the accessory olfactory bulb; layers IV and V of the cerebral neocortex; medial septal nucleus; nucleus of the diagonal band; bed nucleus of the stria terminalis; globus pallidus; ventral pallidum; paraventricular nucleus; supraoptic nucleus; zona incerta; dorsal, lateral, and posterior hypothalamic areas; amygdaloid nuclei; medial habenular nucleus; ventral tegmental area; midbrain periaqueductal gray; interpeduncular nuclei; substantia nigra pars compacta; linear, median, dorsal, and pontine raphe nuclei; posteromedial tegmental nucleus; sphenoid nucleus; nucleus of the solitary tract; intermediate and rostroventrolateral reticular nuclei; and lamina II of the caudal spinal trigeminal nucleus and spinal dorsal horn. These findings are discussed in relation to the physiological functions associated with neuromedin K.}, author = {Ding, Yu and Shigemoto, Ryuichi and Takada, Masahiko and Ohishi, Hitoshi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {2}, pages = {290 -- 310}, publisher = {Wiley-Blackwell}, title = {{Localization of the neuromedin K receptor (NK3) in the central nervous system of the rat}}, doi = {10.1002/(SICI)1096-9861(19960108)364:2<290::AID-CNE8>3.0.CO;2-0}, volume = {364}, year = {1996}, } @article{2572, abstract = {The distribution of the mRNA for a pituitary adenylate cyclase- activating polypeptide (PACAP) receptor (PACAP-R) was examined in the rat brain, and also in the hypophysis and pineal gland, by in situ hybridization with a specific 35S-labeled riboprobe which was generated from a rat PACAP-R cDNA clone. In the brain, expression of PACAP-R mRNA was most prominent in the periglomerular and granule cells of the olfactory bulb, granule cells of the dentate gyrus, supraoptic nucleus, and area postrema. The expression was also intense in the piriform, cingulate, and retrosplenial cortices, pyramidal cells in CA2, non-pyramidal cells in CA1- CA3, neuronal cells in the hilus of the dentate gyrus, lateral septal nucleus, intercalated amygdaloid nucleus, anterodorsal thalamic nucleus, most of the midline and intralaminar thalamic nuclei, many regions of the hypothalamus, dorsal motor nucleus of the vagus nerve, hypoglossal nucleus, and lateral reticular nucleus. No significant expression was detected in the mitral and tufted cells in the olfactory bulb, pyramidal cells in CA1 and CA3, posterior nuclear group of the thalamus, dorsal lateral geniculate nucleus, and Purkinje, Golgi, and granule cells in the cerebellar cortex. Moderate-to-weak expression was further observed in many other regions of the brain. In the cerebellar cortex, presumed Bergmann gila cells showed moderate expression. In the hypophysis, the expression was moderate in the anterior lobe, and weak to moderate in the posterior lobe; no significant expression was observed in the intermediate lobe. In the pineal gland, the expression was very weak, if any. Thus, the expression of PACAP-R was detected not only on neuronal cells but also on some particular glial cells. The present study has shown, for the first time, the exact site of PACAP-R expression in the brain and hypophysis. Although the functional significance of PACAP and PACAP-R in the brain still remains to be clarified, the present results are considered to provide some direction for future functional studies.}, author = {Hashimoto, Hitoshi and Nogi, Hiroyuki and Mori, Kensaku and Ohishi, Hitoshi and Shigemoto, Ryuichi and Yamamoto, Kyohei and Matsuda, Toshio and Mizuno, Noboru and Nagata, Shigekazu and Baba, Akemichi}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {4}, pages = {567 -- 577}, publisher = {Wiley-Blackwell}, title = {{Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: An in situ hybridization study}}, doi = {10.1002/(SICI)1096-9861(19960805)371:4<567::AID-CNE6>3.3.CO;2-M}, volume = {371}, year = {1996}, } @article{2491, abstract = {The distribution of mRNAs for metabotropic glutamate receptors, mGluR4 and mGluR7, which are highly sensitive for L-2-amino-4-phosphonobutyrate (L- AP4), was examined in the central nervous system of the rat by in situ hybridization. In general, the hybridization signals of mGluR7 mRNA were more widely distributed than those of mGluR4 mRNA, and differential expression of mGluR4 mRNA and mGluR7 mRNA was clearly indicated in some brain regions. Intense or moderate expression of mGluR4 mRNA was detected in the granule cells of the olfactory bulb and cerebellum, whereas no significant expression of mGluR7 mRNA was found in these cells. In other neurons or regions where mGluR7 mRNA was intensely or moderately expressed, no significant expression of mGluR4 mRNA was observed. Such were the mitral and tufted cells of the olfactory bulb; anterior olfactory nucleus; neocortical regions; cingulate cortex; retrosplenial cortex; piriform cortex; perirhinal cortex; CA1; CA3; granule cells of the dentate gyrus; superficial layers of the subicular cortex; deep layers of the entorhinal, parasubicular, and presubicular cortices; ventral part of the lateral septal nucleus; septohippocampal nucleus; triangular septal nucleus; nuclei of the diagonal band; bed nucleus of the stria terminalis; ventral pallidum; claustrum; amygdaloid nuclei other than the intercalated nuclei; preoptic region; hypothalamic nuclei other than the medial mammillary nucleus; ventral lateral geniculate nucleus; locus coeruleus; Purkinje cells; many nuclei of the lower brainstem other than the superior colliculus, periaqueductal gray, interpeduncular nucleus, pontine nuclei, and dorsal cochlear nucleus; and dorsal horn of the spinal cord. Both mGluR4 mRNA and mGluR7 mRNA were moderately or intensely expressed in the olfactory tubercle, superficial layers of the entorhinal cortex, CA4, septofimbrial nucleus, intercalated nuclei of the amygdala, medial mammillary nucleus, many thalamic nuclei, and pontine nuclei. Intense expression of both mGluR4 mRNA and mGluR7 mRNA was further detected in the trigeminal ganglion and dorsal root ganglia, whereas no significant expression of them was found in the pterygopalatine ganglion and superior cervical ganglion. The results indicate differential roles of the L-AP4-sensitive metabotropic glutamate receptors in the glutamatergic nervous system.}, author = {Ohishi, Hitoshi and Akazawa, Chihiro and Shigemoto, Ryuichi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {4}, pages = {555 -- 570}, publisher = {Wiley-Blackwell}, title = {{Distributions of the mRNAs for L-2-amino-4-phosphonobutyrate-sensitive metabotropic glutamate receptors, mGluR4 and mGluR7, in the rat brain}}, doi = {10.1002/cne.903600402}, volume = {360}, year = {1995}, } @article{2489, abstract = {Five N-methyl-D-aspartate (NMDA) receptor subunits have been identified thus far: NR1, NR2A, NR2B, NR2C, and NR2D. Here, we have analyzed the expression patterns of mRNAs for the NMDA receptor subunits in the developing and adult rats by in situ hybridization. The developmental changes of the expression patterns were most salient in the cerebellum. In the external granular layer, hybridization signals of mRNAs for NR1, NR2A, NR2B, and NR2C appeared by postnatal day 3, but no NR2D mRNA was expressed at any developmental stage examined. The NR1 mRNA was expressed in all cerebellar neurons at all developmental stages examined. The signals for the NR2A mRNA appeared in Purkinje cells and granule cells during the second postnatal week. The signals for the NR2B mRNA in granule cells were seen transiently during the first 2 weeks after birth. The signals for NR2C mRNA appeared in granule cells and glial cells during the second postnatal week. The signals for NR2D mRNA appeared transiently in Purkinje cells during the first 8 postnatal days; in adult rats, these were seen in stellate and Golgi cells. In the cerebellar nuclei, mRNAs for NR1, NR2A, NR2B, and NR2D were more or less expressed on postnatal day 0, while expression signals for the NR2C mRNA were first detected in postnatal day 14. Thus, the most conspicuous changes of expression patterns were observed in the cerebellar cortex during the first 2 weeks after birth, when development and maturation of the cerebellum proceed most rapidly.}, author = {Akazawa, Chihiro and Shigemoto, Ryuichi and Bessho, Yasumasa and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {1}, pages = {150 -- 160}, publisher = {Wiley-Blackwell}, title = {{Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats}}, doi = {10.1002/cne.903470112}, volume = {347}, year = {1994}, } @article{2549, abstract = {In an attempt to reveal the function sites of substance P (SP) in the central nervous system (CNS), the distribution of SP receptor (SPR) was immunocytochemically investigated in adult rat and compared with that of SP- positive fibers. SPR-like immunoreactivity (LI) was mostly localized to neuronal cell bodies and dendrites. Neurons with intense SPR-LI were distributed densely in the cortical amygdaloid nucleus, hilus of the dentate gyrus, locus ceruleus, rostral half of the ambiguus nucleus, and intermediolateral nucleus of the thoracic cord; moderately in the caudatoputamen, nucleus accumbens, olfactory tubercle, median, pontine, and magnus raphe nuclei, laminae I and III of the caudal subnucleus of the spinal trigeminal nucleus, and lamina I of the spinal cord; and sparsely in the cerebral cortex, basal nucleus of Meynert, claustrum, gigantocellular reticular nucleus, and lobules IX and X of the cerebellar vermis. Neurons with weak to moderate SPR-LI were distributed more widely throughout the CNS. The regional patterns of distribution of SPR-LI were not necessarily the same as those of SP-positive fibers. The entopeduncular nucleus, substantia nigra, and lateral part of the interpeduncular nucleus showed intense SP-LI but displayed almost no SPR-LI. Conversely, the hilus of the dentate gyrus, anterodorsal thalamic nucleus, central nucleus of the inferior colliculus, and dorsal tegmental nucleus showed intense to moderate SPR-LI but contained few axons with SP-LI. These findings confirmed the presence of the 'mismatch' problem between SP and SPR localizations. However, the distribution of SPR- LI was quite consistent with that of the SP-binding activity, which has been studied via autoradiography. This indicates that the sites of SPR-LI revealed in the present study represent most, if not all, sites of SP-binding activity.}, author = {Nakaya, Yoshifumi and Kaneko, Takeshi and Shigemoto, Ryuichi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {2}, pages = {249 -- 274}, publisher = {Wiley-Blackwell}, title = {{Immunohistochemical localization of substance P receptor in the central nervous system of the adult rat}}, doi = {10.1002/cne.903470208}, volume = {347}, year = {1994}, } @article{2487, abstract = {Distribution of the mRNA for a metabotropic glutamate receptor, mGluR3, which is coupled to the inhibitory cAMP cascade, was examined in the central nervous system of the adult albino rat by in situ hybridization. The hybridization signals of mGluR3 were detected not only on neuronal cells but also on many glial cells throughout the brain and spinal cord. In the neuronal cells, prominent expression of mGluR3 mRNA was seen in the thalamic reticular nucleus. Moderately labeled neurons were seen in the anterior olfactory nucleus, cerebral neo- and mesocortical regions, lateral amygdaloid nucleus, ventral part of the basolateral amygdaloid nucleus, dorsal endopiriform nucleus, supraoptic nucleus, superficial layers of the superior colliculus, inferior colliculus, interpeduncular nucleus, superior olivary nuclei, and Golgi cells in the cerebellar cortex. Weakly labeled neurons were observed in the striatum, nucleus accumbens, ventral pallidum, globus pallidus, entopeduncular nucleus, lateral hypothalamic area, hypothalamic paraventricular nucleus, medial habenular nucleus, anterior pretectal nucleus, Barrington's nucleus, Nucleus O, paragenual nucleus, trigeminal sensory complex, cochlear nuclei, dorsal motor nucleus of the trigeminal nerve, dorsal cap of the inferior olive, spinal dorsal horn, and lamina X of the spinal cord. The stellate cells in the cerebellar cortex, and neurons in the deep cerebellar nuclei were also labeled weakly. The granule cell layer of the dentate gyrus, as a whole, appeared to be labeled intensely, but each of the granule cells was labeled only weakly. No significant labeling was detected in the mitral and tufted cells in the olfactory bulb, hippocampal pyramidal cells, Purkinje and granule cells in the cerebellar cortex, or somatic motoneurons. The distribution of mGluR3 mRNA in particular neurons and glial cells indicates specific roles of mGluR3 in the glutamatergic system of the central nervous system.}, author = {Ohishi, Hitoshi and Shigemoto, Ryuichi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {2}, pages = {252 -- 266}, publisher = {Wiley-Blackwell}, title = {{ Distribution of the mRNA for a metabotropic glutamate receptor (mGluR3) in the rat brain: An in situ hybridization study}}, doi = {10.1002/cne.903350209}, volume = {335}, year = {1993}, }