Immunohistochemical Localization of α-Mannosidase During Postnatal Development of the Rat Cerebellum

The localization of alpha-D-mannosidase in the rat cerebellum was studied by using indirect immunohistochemistry at both optical and electron microscopic levels. In the adult the enzyme is particularly concentrated in the dendrites and cell bodies of Purkinje cells, basket cells, and Golgi neurons in the cerebellar cortex and in the cytoplasm and dendrites of deep nuclei neurons. The cytoplasm of granule cells is poorly stained, whereas parallel fibers, white matter, Bergman fibers, and Golgi epitheloid cell perikarya show virtually no staining. Electron microscopy suggests that most of the staining is found in the cytosol, although some staining is found in the postsynaptic densities of the synapses between parallel fibers and Purkinje dendrites. The pattern of staining was followed throughout the postnatal development of the rat cerebellum. At bith an intense and diffuse staining is found in all cells except those of the external germinative layer. At the 6th postnatal day, Purkinje cell bodies and apical cones are strongly labeled. From the 13th day on the pattern is very similar to that found in the adult. However, at the 18th postnatal day (when compared with the other structures), the staining of Purkinje cell dendrites seems to be higher than at all other ages. These data are correlated with biochemical studies and discussed in relation to the possible role of this enzyme during the postnatal development of the rat cerebellum.     

Osteocalcin- and Osteopontin-Containing Neurons in the Rat Hind Brain

Immunohistochemistry for osteocalcin (OC) and osteopontin (OPN) was performed to know their distributions in the hind brain of adult rats. OC- and OPN-immunoreactivity (-ir) were detected in neuronal cell bodies, including perikarya and proximal dendrites and the neuropil. In the cranial nerve motor nuclei, numerous OC- and OPN-immunoreactive (-ir) neurons were detected. The neuropil in the cranial motor nuclei mostly showed strong OC- and OPN-staining intensity. The cranial nerve sensory nuclei and other relay and modulating structures in the lower brain stem also contained various numbers of OC- and OPN-ir neurons. The staining intensities in the neuropil were varied among these regions. In the cerebellar cortex, Purkinje cells and granule cells showed OPN-ir but not OC-ir. However, OC- and OPN-ir neurons were abundantly distributed throughout the cerebellar nuclei. The neuropil in the cerebellar nuclei showed moderate OC-ir and strong OPN-ir staining intensities. These findings indicate that the distribution patterns of OC- and OPN-ir neurons were similar in many structures within the hind brain. OC may play a role in modulating neuroprotective function of OPN.     

Visual corticopontine and tectopontine projections in the macaque.

We studied projections from extrastriate visual areas and the superior colliculus to the pontine nuclei of monkeys using degeneration staining and transport of wheatgerm agglutinin horseradish peroxidase, and 3H amino acids. The superior colliculus and the extrastriate cortical visual areas both project to the ipsilateral dorsolateral region of the pontine nuclei. The projections from extrastriate visual cortex occupy a much larger territory within the pontine nuclei than those from the superior colliculus. The superficial laminae of the superior colliculus project only to the ipsilateral pontine nuclei. The projection to the contralateral nucleus reticularis tegmenti pontis arises from cells in deeper laminae within the superior colliculus.     

Influence of adult Schwann cells and olfactory ensheathing glia on axon--target cell interactions in the CNS: a comparative analysis using a retinotectal co-graft model

We used an in vivo transplant approach to examine how adult Schwann cells and olfactory ensheathing glia OEG influence the specificity of axon-target cell interactions when they are introduced into the CNS. Populations of either Schwann cells or OEG were mixed with dissociated fetal tectal cells presumptive superior colliculus and, after reaggregation, pieces were grafted onto newborn rat superior colliculus. Both glial types were prelabeled with lentiviral vectors encoding green fluorescent protein. Grafts rapidly established fiber connections with the host and retinal projections into co-grafts were assessed 656 days posttransplantation by injecting cholera toxin B into host eyes. In control rats that received pure dissociated-reaggregated tectal grafts, retinal ganglion cell RGC axons selectively innervated defined target areas, corresponding to the retinorecipient layer in normal superior colliculus. The pattern of RGC axon ingrowth into OEG containing co-grafts was similar to that in control grafts. However, in Schwann cell co-grafts there was reduced host retinal input into presumptive target areas and many RGC axons were scattered throughout the neuropil. Given that OEG in co-grafts had minimal impact on axon-target cell recognition, OEG might be an appropriate cell type for direct transplantation into injured neuropil when attempting to stimulate specific pathway reconstruction.     

Evidence for a possible glycinergic inhibitory neurotransmission in the midbrain and rostral pons of the rat studied by gephyrin

The data on the glycinergic transmission in the rostral brainstem are both few and controversial. The present report provides evidence for a possible glycinergic transmission in Sprague-Dawley rats, based on observations of immunocytochemical labeling for gephyrin, a 93 kDa protein and a component of the functional glycine receptor. A monoclonal antibody against gephyrin was used, and the reaction product was visualized by means of avidin-biotin-peroxidase procedure. The reaction product in midbrain and rostral pons was found in neuronal perikarya and in proximal dendrites but in some cases the most distal dendritic branches were also labeled. The neuropil usually displayed a moderate staining with finely granulated reaction product. The most significant immunocytochemical signal was mainly encountered in large and medium-sized neuronal populations of the motor cranial nerve nuclei (III, IV, V), in the reticular formation (laterodorsal tegmental nucleus, pedunculopontine tegmental nucleus, deep mesencephalic nucleus), in the red nucleus, in the intermediate and deep gray strata of the superior colliculus. Only in the substantia nigra and the inferior colliculus the parvocellular cell populations were mainly labeled. The present data suggest a significant inhibitory glycinergic neurotransmission in the rostral brainstem, probably mediated by interneurons.     

Ascending and descending projections to the inferior colliculus in the rat

The ascending and descending projections to the central nucleus of the inferior colliculus (IC) were studied with the aid of retrograde transport of horseradish peroxidase (HRP). HRP-labelled cells were found in contralateral cochlear nuclei, where the majority of different cell types was stained. Few labelled cells were observed in the ipsilateral cochlear nuclei. HRP-positive neurones were found in all nuclei of the superior olivary complex on the ipsilateral side with the exception of the medial nucleus of the trapezoid body, which was never labelled either ipsilaterally or contralaterally. The largest concentration of HRP-labelled cells was usually observed in the ipsilateral superior olivary nucleus. Smaller numbers of labelled cells were present in contralateral nuclei of the superior olivary complex. Massive projections to the inferior colliculus were found from the contralateral and ipsilateral dorsal nucleus of the lateral lemniscus and ipsilateral ventral nucleus of the lateral lemniscus. Many neurones of the central and external nuclei of the contralateral inferior colliculus were labelled with HRP. Topographic organisation of the pathways ascending to the colliculus was expressed in the cochlear nuclei, lateral superior olivary nucleus and in the dorsal nucleus of the lateral lemniscus. HRP--positive cells were found in layer V of the ipsilateral auditory cortex, however, the evidence for topographic organisation was lacking.     

Electron microscopic localization and experimental modification of NADPH-diaphorase activity in crustacean sensory axons

The origin and ultrastructural localization of NADPH-diaphorase (NADPH-d) in the olfactory afferent pathway of the crayfishPacifastacus leniusculus was investigated by means of histochemical techniques. Sensory axons in the antennular nerve and the olfactory lobe glomeruli of normal animals expressed NADPH-d staining properties. The NADPH-d staining of each glomerulus was regionalized showing pronounced staining in the apical cap-region. Following ablation of the chemosensory input for 30 days, the staining properties of the antennular nerve and the glomeruli were reduced. At the electron microscopic level, the NADPH-d precipitate was found to be distributed on various membranes in neuronal profiles and glial cells. Stained neuronal profiles were frequently observed in the glomeruli, whereas the number of positive glial cells was low. Almost all NADPH-d positive profiles in the neuropil had an intraglomerular localization. The present findings suggest that NADPH-d in the crayfish olfactory lobe neuropil is localized to terminals of olfactory sensory axons.     

HISTOCHEMICAL MAPPING OF LACTATE DEHYDROGENASE AND MONOAMINE OXIDASE IN THEMEDULLA OBLONGATA AND CEREBELLUM OF SQUIRREL MONKEY (SAIMIRI SCIUREUS)

Abstract— —The gross distribution of LDH and MAO was studied in a caudo-cranial series of 50 μ thick sections through the medulla oblongata and cerebellum. In general, LDH exhibited a stronger reaction in the neuropil and in the perikarya, whereas MAO showed moderate activity in the neurons and mild to moderate activity in the neuropil. The axonal processes and nerve fibres showed comparatively stronger MAO activity. The nuclei gracilis, cuneatus medialis and lateralis, cranial nerve nuclei, olivaris inferior, vestibularis and cochlearis nuclei showed particularly strong LDH and equally weak MAO activities. The lateral part of the formato reticularis myelencephali showed much more MAO than did the medial part, whereas the LDH reaction was uniformly strong. The reticularis lateralis showed uniformly strong LDH and very mild MAO activities.
In the cerebellar cortex, the MAO activity was concentrated in the molecular layer and nerve fibre layer, whereas LDH activity was particularly strong in the Purkinje cells and their processes in the molecular layer. The cerebellar nuclei showed strong LDH and weak MAO in the neutrons and stronger MAO and moderate LDH in the neuropil.     

Intrinsic organization of snake lateral cortex

Lateral cortex is the most laterally placed of the four cortical areas in snakes. Earlier studies suggest that it is composed of several subdivisions but provide no information on their organization. This paper first investigates the structure of lateral cortex in boa constrictors (Constrictor constrictor), garter snakes (Thamnophis sirtalis), and banded water snakes (Natrix sipedon) using Nissl and Golgi preparations; and secondly examines the relation of main olfactory bulb projections to the subdivisions of lateral cortex using Fink-Heimer and electron microscopic preparations. Lateral cortex is divided on cytoarchitectonic grounds into two major parts called rostral and caudal lateral cortex. Each part is further divided into dorsal and ventral subdivisions so that lateral cortex has a total of four subdivisions: dorsal rostral lateral cortex (drL), ventral rostral lateral cortex (vrL), dorsal caudal lateral cortex (dcL) and ventral caudal lateral cortex (vcL). Systematic analyses of Golgi preparations indicate that the rostral and caudal parts each contain distinct populations of neurons. Rostral lateral cortex contains bowl cells whose dendrites arborize widely in the outer cortical layer (layer 1). The axons of some bowl cells can be traced medially into dorsal cortex, dorsomedial cortex and medial cortex. Caudal lateral cortex contains pyramidal cells whose somata occur in layers 2 and 3 and whose dendrites extend radially up to the pial surface. In addition, three populations of neurons occur in both rostral and caudal lateral cortex. Stellate cells occur in all three layers and have dendrites which arborize in all directions. Double pyramidal cells occur primarily in layer 2 and have dendrites which form two conical fields whose long axes are oriented radially. Horizontal cells occur in layer 3 and have dendrites oriented concentric with the ependyma. Fink-Heimer preparations of snakes which underwent lesions of the main olfactory bulb show that the primary olfactory projections to cortex are bilateral and restricted precisely to rostral lateral cortex. Electron microscopic degeneration experiments indicate that the olfactory bulb fibers end as terminals which have clear, spherical vesicles and asymmetric active zones. The majority are presynaptic to dendritic spines in outer layer 1. These studies establish that lateral cortex in snakes is heterogeneous and contains two major parts, each containing two subdivisions. The rostral and caudal parts have characteristic neuronal populations. Primary olfactory input is restricted to rostral lateral cortex and seems to terminate heavily on the distal dendrites of bowl cells. Axons of some of these cells leave lateral cortex, so that the rostral lateral cortex forms a direct route by which olfactory information reaches other cortical areas. The functional role of caudal lateral cortex is not clear.     

Cytochrome oxidase staining reveals functionally important activity bands in the olfactory epithelium of newborn rat

We used cytochrome oxidase (CytOx) staining intensity, which is correlated with neuronal functional activity, to evaluate maturity and functionality of newborn rat olfactory epithelium (OE) and olfactory receptor neurons (ORNs). Nasal olfactory tissue of neonatal rats was stained with CytOx and analyzed qualitatively and quantitatively. Results revealed that newborn OE shows six differentially stained horizontal bands. Bands run parallel to the OE surface and were categorized as very light, medium or darkly stained. A narrow and pale Band 1 overlapped with horizontal basal cells. Next, a wide and lightly stained Band 2 was observed that coincides with the globose basal cell layer and immature ORNs, deep in OE. Next apically, a medium-staining Band 3 overlapped with ORN perikarya. Closer to the surface, a medium to light Band 4 was discerned where dendrites of mature ORNs normally occur. This band was interrupted with lighter areas due to the presence of supporting cells nuclei. Next, a superficial but dark Band 5 occurred, populated by the apical portions of ORN dendrites and their ciliated knobs and by supporting cell apices; mitochondria in apices of supporting cells contribute predominantly to dense staining of this Band 5. Apical to Band 5, a thin and fairly light Band 6 was observed which overlaps with the mucus layer that contains part of the ORN knobs, their cilia and supporting cell microvilli. Along the length of ORN dendrites, apical segments just below the ORN knobs, and wide basal segments showed a darker staining than the middle segments implying “microzones” of higher neural activity within the most apical and basal regions of dendrites. Our findings agree with ultrastructural studies showing a presence of mitochondria in knobs, basal portions of ORN dendrites and in OE supporting cell apices, suggesting that apical regions of both olfactory and supporting cells near the surfaces are metabolically most active, in odorant detection, signal processing, and detoxification, the latter for supporting cells.     

Immunohistochemical mapping of perineuronal nets containing chondroitin unsulfate proteoglycan in the rat central nervous system

Subsets of neurons ensheathed by perineuronal nets containing chondroitin unsulfate proteoglycan have been immunohistochemically mapped throughout the rat central nervous system from the olfactory bulb to the spinal cord. A variable proportion of neurons were outlined by immunoreactivity for the monoclonal antibody (Mab 1B5), but only after chondroitinase ABC digestion. In forebrain cortical structures the only immunoreactive nets were around interneurons; in contrast, throughout the brainstem and spinal cord a large proportion of projection neurons were surrounded by intense immunoreactivity. Immunoreactivity was ordinarily found in the neuropil between neurons surrounded by an immunopositive net. By contrast, within the pyriform cortex the neuropil of the plexiform layer was intensely immunoreactive even though no perineuronal net could be found. The presence of perineuronal nets could not be correlated with any single class of neurons; however a few functionally related groups (e.g., motor and motor-related structures: motor neurons both in the spinal cord and in the efferent somatic nuclei of the brainstem, deep cerebellar nuclei, vestibular nuclei; red nucleus, reticular formation; central auditory pathway: ventral cochlear nucleus, trapezoid body, superior olive, nucleus of the lateral lemniscus, inferior colliculus, medial geniculate body) were the main components of the neuronal subpopulation displaying chondroitin unsulfate proteoglycans in the surrounding extracellular matrix. The immunodecorated neurons found in the present study and those shown by different monoclonal antibodies or by lectin cytochemisty, revealed consistent overlapping of their distribution patterns.     

Autoradiographic distribution of high affinity muscarinic and nicotinic cholinergic receptors labeled with [3H]acetylcholine in rat brain

The relative distribution of muscarinic and nicotinic cholinergic receptors labeled with [3H]acetylcholine was determined using autoradiography. [3H]Acetylcholine binding to high affinity muscarinic receptors was similar to what has been described for an M-2 distribution: highest levels of binding occurred in the pontine and brainstem nuclei, anterior pretectal area and anteroventral thalamic nucleus, while lower levels occurred in the caudate-putamen, accumbens nucleus and primary olfactory cortex. Nicotinic receptors were labeled with [3H]acetylcholine to the greatest extent in the interpeduncular nucleus, several thalamic nuclei, medial habenula, presubiculum and superior colliculus, and to the least extent in the hippocampus and inferior colliculus. By using autoradiography to localize cholinergic binding sites throughout the brain it was observed that the distributions of high affinity muscarinic and nicotinic sites labeled with the endogenous ligand, [3H]acetylcholine are different from each other and are different from distributions of muscarinic and nicotinic sites labeled with muscarinic and nicotinic antagonists.     

Immunohistochemical Studies of the Cellular Changes in the Peripheral Olfactory System After Zinc Sulfate Nasal Irrigation

The peripheral olfactory system has a remarkable capacity for repair. We have performed an immunohistochemical study of the cellular changes that occur after zinc sulfate irrigation of the nasal cavity. The rapid loss of epithelial cells was followed by the proliferation of basal cells and the restoration of the epithelium with olfactory tissue. Horizontal basal cell markers, anti-cytokeratin 5/6 (CK5/6), and the Bandeiraea simplicifolia (BS-1) lectin initially co-localized on day 1 after treatment but rapidly displayed a disparity in their staining profile, with CK5/6 immunoreactive cells having a profile more akin to cells expressing the sustentacular marker cytokeratin 18 (CK18). This suggests CK5/6 and BS-1 label a different subset of horizontal basal cells. Axonal degeneration and regeneration was studied with a panel of markers to olfactory receptor neurons, their terminals, and olfactory bulb dendrites. The glial cells of the peripheral olfactory system, olfactory ensheathing cells, remained in position, with little change in immunoreactivity to laminin, although an increase in the expression of glial fibrillary acidic protein was observed. The events and the extent of reconstitution of the olfactory system after degeneration serves as a foundation for future studies designed to understand the unique regenerative capacity of the olfactory system.     

大鼠脑内代谢型谷氨酸受体5亚型(mGluR5)定位分布的免疫细胞化学研究

本研究用免疫细胞化学技术观察了大鼠脑内参与兴奋性突触传递的代谢型谷氨酸受体5亚型(mGluR5)的精确定位分布.mGluR5阳性浓染的神经元胞体和纤维密集地分布于大脑皮质浅层、嗅球、伏核、尾壳核、前脑基底部、隔区、苍白球、腹侧苍白球、海马CA1和CA2区、下丘中央核、被盖背侧核和三叉神经脊束核尾侧亚核浅层;淡染而稀疏的mGluR5阳性神经元胞体和纤维见于屏状核、终纹床核、杏仁中央核、丘脑部分核团、上丘浅灰质层、外侧丘系背侧核和延髓中央灰质.     

Long-lasting effects of audiogenic seizures on neurotransmitter amino acids in Rb mice

The existence of long-lasting (15–18 h) alterations of neurotrasmitter amino acid levels following a single or repeated acoustic stimulations in audiogenic seizure-prone Rb1 and Rb2 mice and suizure-resistant Rb3 mice were investigated. The levels of glutamate, aspartate, glycine, taurine, and of some of their precursors: glutamine and serine were determined. Fourteen brain areas were examined. Alterations were found only in 6 brain areas (pons, olfactory bulbs, superior colliculus, inferior colliculus, olfactory tubercles and raphe). Most frequent occuring changes were observed in pons and olfactory tubercles. These changes concerned mainly the excitatory amino acids, glutamate, and aspartate. Alterations of taurine, glycine and serine were also recorded.Abbreviations GABA 4-aminobutyrate - Tau taurine - Gly glycine - Asp aspertate - Glu glutamate - Gln glutamine - Ser serine - OB olfactory bulbs - OT olfactory tubercles - Sr striatum - Se septum - Hy hypothalamus - Th thalamus - Hi hippocampus - A amygdala - SC superior colliculus - IC inferior colliculus - FC frontal cortex - C cerebellum - P pons medulla - Ra raphe - AA neurotransmitter amino acids - I inhibitory - E excitatory - SSL steady-state level Plesant memories of Lawrence Austin's sojourn in my group at Strasbourg gather upon me when I dedicate this article on this occasion for the contribution that Lawrence Austin has made for the cause of neurochemical researchers.     

Immunocytochemical Localization of TASK-3 Protein (K2P9.1) in the Rat Brain

Among all K2P channels, TASK-3 shows the most widespread expression in rat brain, regulating neuronal excitability and transmitter release. Using a recently purified and characterized polyclonal monospecific antibody against TASK-3, the entire rat brain was immunocytochemically analyzed for expression of TASK-3 protein. Besides its well-known strong expression in motoneurons and monoaminergic and cholinergic neurons, TASK-3 expression was found in most neurons throughout the brain. However, it was not detected in certain neuronal populations, and neuropil staining was restricted to few areas. Also, it was absent in adult glial cells. In hypothalamic areas, TASK-3 was particularly strongly expressed in the supraoptic and suprachiasmatic nuclei, whereas other hypothalamic nuclei showed lower protein levels. Immunostaining of hippocampal CA1 and CA3 pyramidal neurons showed strongest expression, together with clear staining of CA3 mossy fibers and marked staining also in the dentate gyrus granule cells. In neocortical areas, most neurons expressed TASK-3 with a somatodendritic localization, most obvious in layer V pyramidal neurons. In the cerebellum, TASK-3 protein was found mainly in neurons and neuropil of the granular cell layer, whereas Purkinje cells were only faintly positive. Particularly weak expression was demonstrated in the forebrain. This report provides a comprehensive overview of TASK-3 protein expression in the rat brain.     

Distribution and Developmental Regulation of Metabotropic Glutamate Receptor 7a in Rat Brain

Abstract: To determine the regional and cellular distribution of the metabotropic glutamate receptor mGluR7a, we used rabbit anti-peptide polyclonal-targeted antibodies against the C-terminal domain of mGluR7a. Here we report that immunocytochemistry at the light-microscopic level revealed that mGluR7a is widely distributed throughout the adult rat brain, with a high level of expression in sensory areas, such as piriform cortex, superior colliculus, and dorsal cochlear nucleus. In most brain structures, mGluR7a immunoreactivity is characterized by staining of puncta and fibers. However, in some regions, including the locus ceruleus, cerebellum, and thalamic nuclei, both cell bodies and fibers are immunopositive. The changes in levels of mGluR7a during development were investigated with immunoblotting and immunocytochemical analysis. Immunoblot analysis revealed that the levels of mGluR7a are differentially regulated across brain regions during postnatal development. In cortical regions (hippocampus, neocortex, and olfactory cortex), mGluR7a levels were highest at postnatal day 7 (P7) and P14, then declined in older rats. In contrast, mGluR7a levels were highest at P7 in pons/medulla and cerebellum and decreased markedly between P7 and P14. In these regions, mGluR7a immunoreactivity was at similar low levels at P14 and P21 and in adults. Immunocytochemical analysis revealed that staining for mGluR7a was exceptionally high in fiber tracts in P7 animals relative to adults. Furthermore, the pattern of mGluR7a immunoreactivity in certain brain structures, including cerebellum, piriform cortex, and hippocampus, was significantly different in P7 and adult animals. In summary, these data suggest that mGluR7a is widely distributed throughout the rat brain and that this receptor undergoes a dynamic, regionally specific regulation during postnatal development.     

Long-term effects of alloxan-induced diabetes on the nucleus ventralis posterolateralis in the thalamus of the rat.

The present paper describes the long-term ultrastructural changes in the nucleus ventralis posterolateralis of the thalamus of male Wistar rats after alloxan-induced diabetes. Degenerating dendrites were characterized by an electron-dense cytoplasm with scattered endoplasmic reticulum and ribosomes. Degenerating axon terminals were characterized by an electron-dense cytoplasm and clustering of small spherical agranular vesicles. Degenerating axon terminals formed axosomatic synapses with seemingly normal cell bodies and axodendritic synapses with normal as well as degenerating dendrites. Degenerating axons (both myelinated and unmyelinated) were readily encountered in the neuropil. Activated microglial and astrocytic cells in the neuropil were in the process of phagocytosis or had residua in their cytoplasm.     

Localisation of Formyl-Peptide Receptor 2 in the Rat Central Nervous System and Its Role in Axonal and Dendritic Outgrowth

Arachidonic acid and docosahexaenoic acid (DHA) released by the action of phospholipases A₂ (PLA₂) on membrane phospholipids may be metabolized by lipoxygenases to the anti-inflammatory mediators lipoxin A4 (LXA4) and resolvin D1 (RvD1), and these can bind to a common receptor, formyl-peptide receptor 2 (FPR2). The contribution of this receptor to axonal or dendritic outgrowth is unknown. The present study was carried out to elucidate the distribution of FPR2 in the rat CNS and its role in outgrowth of neuronal processes. FPR2 mRNA expression was greatest in the brainstem, followed by the spinal cord, thalamus/hypothalamus, cerebral neocortex, hippocampus, cerebellum and striatum. The brainstem and spinal cord also contained high levels of FPR2 protein. The cerebral neocortex was moderately immunolabelled for FPR2, with staining mostly present as puncta in the neuropil. Dentate granule neurons and their axons (mossy fibres) in the hippocampus were very densely labelled. The cerebellar cortex was lightly stained, but the deep cerebellar nuclei, inferior olivary nucleus, vestibular nuclei, spinal trigeminal nucleus and dorsal horn of the spinal cord were densely labelled. Electron microscopy of the prefrontal cortex showed FPR2 immunolabel mostly in immature axon terminals or ‘pre-terminals’, that did not form synapses with dendrites. Treatment of primary hippocampal neurons with the FPR2 inhibitors, PBP10 or WRW4, resulted in reduced lengths of axons and dendrites. The CNS distribution of FPR2 suggests important functions in learning and memory, balance and nociception. This might be due to an effect of FPR2 in mediating arachidonic acid/LXA4 or DHA/RvD1-induced axonal or dendritic outgrowth.