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Projection Neurons (projection + neuron)
Kinds of Projection Neurons Selected AbstractsBrain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5 Prevent the Death of Striatal Projection Neurons in a Rodent Model of Huntington's DiseaseJOURNAL OF NEUROCHEMISTRY, Issue 5 2000Esther Pérez-Navarro Abstract: Intrastriatal injection of quinolinate has been proven to be a very useful animal model to study the pathogenesis and treatment of Huntington's disease. To determine whether growth factors of the neurotrophin family are able to prevent the degeneration of striatal projection neurons, cell lines expressing brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) were grafted in the adult rat striatum before quinolinate injection. Three days after lesioning, ongoing cell death was assessed by in situ detection of DNA fragmentation. In animals grafted with the control cell line, quinolinate injection induced a gradual cell loss that was differentially prevented by intrastriatal grafting of BDNF-, NT-3-, or NT-4/5-secreting cells. Seven days after lesioning, we characterized striatal projection neurons that were protected by neurotrophins. Quinolinate injection, alone or in combination with the control cell line, induced a selective loss of striatal projection neurons. Grafting of a BDNF-secreting cell line prevented the loss of all types of striatal projection neurons analyzed. Glutamic acid decarboxylase 67-, preproenkephalin-, and preprotachykinin A- but not prodynorphin-expressing neurons were protected by grafting of NT-3- or NT-4/5-secreting cells but with less efficiency than the BDNF-secreting cells. Our findings show that neurotrophins are able to promote the survival of striatal projection neurons in vivo and suggest that BDNF might be beneficial for the treatment of striatonigral degenerative disorders, including Huntington's disease. [source] Alcohol Inhibits Spontaneous Activity of Basolateral Amygdala Projection Neurons in the Rat: Involvement of the Endocannabinoid SystemALCOHOLISM, Issue 3 2008Simona Perra Background:, A large body of evidence indicates that the limbic system is involved in the neural processing underlying drug addiction. Among limbic regions, the basolateral nucleus of amygdala (BLA) is implicated in some aspects of the neurobiological mechanisms of drugs of abuse, including alcohol and cannabinoids. It is recently emerging that the endocannabinoid system is involved in many pharmacological and behavioral effects of alcohol. The BLA possesses a very high density of CB1 cannabinoid receptors, and endocannabinoids modulate forms of synaptic plasticity in this region. The aims of our study were first to investigate in vivo the sensitivity of BLA pyramidal neurons to alcohol and second to determine the role of the endocannabinoid system in the acute effects of alcohol. Methods:, We utilized extracellular single cell recordings in urethane anesthetized rats from BLA principal neurons, antidromically identified from their projection site in the nucleus accumbens. Results:, Alcohol (0.25 to 2.0 g/kg i.v.) induced a marked decrease in the spontaneous firing rate of BLA projecting neurons (51.1 ± 16% of baseline at 0.5 g/kg alcohol, p < 0.0001). The involvement of the endogenous cannabinoid system was investigated by administering the CB1 receptor antagonist SR141716A (rimonabant, SR) (1.0 mg/kg i.v.) before alcohol. SR per se did not significantly affect firing rate of BLA neurons, but it prevented the inhibition produced by alcohol (98 ± 18% of baseline firing at 0.5 g/kg alcohol, p < 0.01). Then, we studied the actions of alcohol following a chronic treatment with the CB1 agonist WIN55212-2 (WIN). Animals were administered WIN for 6.5 days (2.0 mg/kg, i.p. twice daily) and alcohol dose,response curves were carried out on firing rate of BLA neurons 24 hours following the last injection of the cannabinoid agonist. In WIN-treated animals the inhibitory effect of alcohol was significantly reduced as compared with controls (95 ± 16% of baseline firing at 0.5 g/kg, p < 0.05). Conclusions:, Our results provide evidence of the involvement of the endocannabinoid system in the effects of alcohol on BLA projection neurons. They also further point to the endocannabinoid system as a possible molecular target in the treatment of alcoholism. [source] R6/2 neurons with intranuclear inclusions survive for prolonged periods in the brains of chimeric miceTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 6 2007Anton Reiner Abstract The R6/2 mouse possesses mutant exon 1 of human Hdh, and R6/2 mice with 150 CAG repeats show neurological abnormalities by 10 weeks and die by 15 weeks. Few brain abnormalities, however, are evident at death, other than widespread ubiquitinated neuronal intranuclear inclusions (NIIs). We constructed R6/2t+/t, , wildtype (WT) chimeric mice to prolong survival of R6/2 cells and determine if neuronal death and/or neuronal injury become evident with longer survival. ROSA26 mice (which bear a lacZ transgene) were used as WT to distinguish between R6/2 and WT neurons. Chimeric mice consisting partly of R6/2 cells lived longer than pure R6/2 mice (up to 10 months), with the survival proportional to the R6/2 contribution. Genotypically R6/2 cells formed NIIs in the chimeras, and these NIIs grew only slightly larger than in 12-week pure R6/2 mice, even after 10 months. Additionally, neuropil aggregates formed near R6/2 neurons in chimeric mice older than 15 weeks. Thus, R6/2 neurons could survive well beyond 15 weeks in chimeras. Moreover, little neuronal degeneration was evident in either cortex or striatum by routine histological stains. Nonetheless, striatal shrinkage and ventricular enlargement occurred, and striatal projection neuron markers characteristically reduced in Huntington's disease were diminished. Consistent with such abnormalities, cortex and striatum in chimeras showed increased astrocytic glial fibrillary acidic protein. These results suggest that while cortical and striatal neurons can survive nearly a year with nuclear and extranuclear aggregates of mutant huntingtin, such lengthy survival does reveal cortical and striatal abnormality brought on by the truncated mutant protein. J. Comp. Neurol. 505:603,629, 2007. © 2007 Wiley-Liss, Inc. [source] Early frontotemporal dementia targets neurons unique to apes and humansANNALS OF NEUROLOGY, Issue 6 2006William W. Seeley MD Objective Frontotemporal dementia (FTD) is a neurodegenerative disease that erodes uniquely human aspects of social behavior and emotion. The illness features a characteristic pattern of early injury to anterior cingulate and frontoinsular cortex. These regions, though often considered ancient in phylogeny, are the exclusive homes to the von Economo neuron (VEN), a large bipolar projection neuron found only in great apes and humans. Despite progress toward understanding the genetic and molecular bases of FTD, no class of selectively vulnerable neurons has been identified. Methods Using unbiased stereology, we quantified anterior cingulate VENs and neighboring Layer 5 neurons in FTD (n = 7), Alzheimer's disease (n = 5), and age-matched nonneurological control subjects (n = 7). Neuronal morphology and immunohistochemical staining patterns provided further information about VEN susceptibility. Results FTD was associated with early, severe, and selective VEN losses, including a 74% reduction in VENs per section compared with control subjects. VEN dropout was not attributable to general neuronal loss and was seen across FTD pathological subtypes. Surviving VENs were often dysmorphic, with pathological tau protein accumulation in Pick's disease. In contrast, patients with Alzheimer's disease showed normal VEN counts and morphology despite extensive local neurofibrillary pathology. Interpretation VEN loss links FTD to its signature regional pattern. The findings suggest a new framework for understanding how evolution may have rendered the human brain vulnerable to specific forms of degenerative illness. Ann Neurol 2006;60:660,667 [source] Olfactory epithelium influences the orientation of mitral cell dendrites during developmentDEVELOPMENTAL DYNAMICS, Issue 2 2005Laura López-Mascaraque Abstract We have established previously that, although the olfactory epithelium is absent in the homozygous Pax-6 mutant mouse, an olfactory bulb-like structure (OBLS) does develop. Moreover, this OBLS contains cells that correspond to mitral cells, the primary projection neurons in the olfactory bulb. The current study aimed to address whether the dendrites of mitral cells in the olfactory bulb or in the OBLS mitral-like cells, exhibit a change in orientation in the presence of the olfactory epithelium. The underlying hypothesis is that the olfactory epithelium imparts a trophic signal on mitral and mitral-like cell that influences the growth of their primary dendrites, orientating them toward the surface of the olfactory bulb. Hence, we cultured hemibrains from wild-type and Pax 6 mutant mice from two different embryonic stages (embryonic days 14 and 15) either alone or in coculture with normal olfactory epithelial explants or control tissue (cerebellum). Our results indicate that the final dendritic orientation of mitral and mitral-like cells is directly influenced both by age and indeed by the presence of the olfactory epithelium. Developmental Dynamics 232:325,335, 2005. © 2004 Wiley-Liss, Inc. [source] Visual experience and age affect synaptic organization in the mushroom bodies of the desert ant Cataglyphis fortisDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2010Sara Mae Stieb Abstract Desert ants of the genus Cataglyphis undergo an age-related polyethism from interior workers involved in brood care and food processing to short-lived outdoor foragers with remarkable visual navigation capabilities. The quick transition from dark to light suggests that visual centers in the ant's brain express a high degree of plasticity. To investigate structural synaptic plasticity in the mushroom bodies (MBs),sensory integration centers supposed to be involved in learning and memory,we immunolabeled and quantified pre- and postsynaptic profiles of synaptic complexes (microglomeruli, MG) in the visual (collar) and olfactory (lip) input regions of the MB calyx. The results show that a volume increase of the MB calyx during behavioral transition is associated with a decrease in MG numbers in the collar and, less pronounced, in the lip. Analysis of tubulin-positive profiles indicates that presynaptic pruning of projection neurons and dendritic expansion in intrinsic Kenyon cells are involved. Light-exposure of dark-reared ants of different age classes revealed similar effects. The results indicate that this structural synaptic plasticity in the MB calyx is primarily driven by visual experience rather than by an internal program. This is supported by the fact that dark-reared ants age-matched to foragers had MG numbers comparable to those of interior workers. Ants aged artificially for up to 1 year expressed a similar plasticity. These results suggest that the high degree of neuronal plasticity in visual input regions of the MB calyx may be an important factor related to behavior transitions associated with division of labor. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 408,423, 2010 [source] The L1-CAM, Neuroglian, functions in glial cells for Drosophila antennal lobe developmentDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2008Weitao Chen Abstract Although considerable progress has been made in understanding the roles of olfactory receptor neurons (ORNs) and projection neurons (PNs) in Drosophila antennal lobe (AL) development, the roles of glia have remained largely mysterious. Here, we show that during Drosophila metamorphosis, a population of midline glial cells in the brain undergoes extensive cellular remodeling and is closely associated with the collateral branches of ORN axons. These glial cells are required for ORN axons to project across the midline and establish the contralateral wiring in the ALs. We find that Neuroglian (Nrg), the Drosophila homolog of the vertebrate cell adhesion molecule, L1, is expressed and functions in the midline glial cells to regulate their proper development. Loss of Nrg causes the disruption in glial morphology and the agenesis of the antennal commissural tract. Our genetic analysis further demonstrates that the functions of Nrg in the midline glia require its ankyrin-binding motif. We propose that Nrg is an important regulator of glial morphogenesis and axon guidance in AL development. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Development and topography of the lateral olfactory tract in the mouse: Imaging by genetically encoded and injected fluorescent markersDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2006Andreas Walz Abstract In mammals, conventional odorants are detected by OSNs located in the main olfactory epithelium of the nose. These neurons project their axons to glomeruli, which are specialized structures of neuropil in the olfactory bulb. Within glomeruli, axons synapse onto dendrites of projection neurons, the mitral and tufted (M/T) cells. Genetic approaches to visualize axons of OSNs expressing a given odorant receptor have proven very useful in elucidating the organization of these projections to the olfactory bulb. Much less is known about the development and connectivity of the lateral olfactory tract (LOT), which is formed by axons of M/T cells connecting the olfactory bulb to central neural regions. Here, we have extended our genetic approach to mark M/T cells of the main olfactory bulb and their axons in the mouse, by targeted insertion of IRES-tauGFP in the neurotensin locus. In NT-GFP mice, we find that M/T cells of the main olfactory bulb mature and project axons as early as embryonic day 11.5. Final innervation of central areas is accomplished before the end of the second postnatal week. M/T cell axons that originate from small defined areas within the main olfactory bulb, as visualized by localized injections of fluorescent tracers in wild-type mice at postnatal days 1 to 3, follow a dual trajectory: a branch of tightly packed axons along the dorsal aspect of the LOT, and a more diffuse branch along the ventral aspect. The dorsal, but not the ventral, subdivision of the LOT exhibits a topographical segregation of axons coming from the dorsal versus ventral main olfactory bulb. The NT-GFP mouse strain should prove useful in further studies of development and topography of the LOT, from E11.5 until 2 weeks after birth. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Lesion-induced neurogenesis in the hypothalamus is involved in behavioral recovery in adult ring dovesDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2006Gang Chen Abstract Although neurogenesis in the brain of adult vertebrates is region dependent, lesion induces generation of new neurons in non-neurogenic brain regions. These findings raise the question of the role of new neurons in brain repair and functional recovery. We addressed this question by applying previous observations that electrolytic lesion induced neurogenesis in the ventromedial nucleus (VMN) of the hypothalamus in adult ring doves. Such lesions disrupted the male's courtship behavior, which could be reinstated after rehabilitation with a female. We investigated whether lesion-induced newborn neurons in the VMN facilitate the recovery of courtship behavior in the lesioned birds. We conducted systematic observations of cytological, morphological, and neuroanatomical changes in the lesioned VMN, and concurrently we monitored behavioral changes. Using a multitude of specific cell markers, we found a well-circumscribed cellular zone that proliferated actively. This highly proliferative zone initially appeared along the periphery of the lesion site, where cells had high levels of expression of neuronal, glial, and neurovascular markers. As newborn neurons matured at the lesion site, the necrosis gradually decreased, whereas a downsized proliferative zone relocated to a region ventral to the VMN. Some of the mature neurons were found to project to the midbrain vocal nuclei. Restoration of these projection neurons coincided with the recovery of courtship vocalization. Finally, we found that a social factor, that is, when the male doves were cohoused with a mate, facilitated neurogenesis and behavioral recovery. These results suggest that lesion-induced neurogenesis contributes to behavioral recovery in adult animals. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Neuronal differentiation and long-term survival of newly generated cells in the olfactory midbrain of the adult spiny lobster, Panulirus argusDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Manfred Schmidt Abstract The fate of continuously generated cells in the soma clusters of the olfactory midbrain of adult spiny lobsters, Panulirus argus, was investigated by in vivo pulse-chase experiments with the proliferation marker 5-bromo-2,-deoxyuridine (BrdU) combined with immunostainings for neuropeptides of mature neurons. A BrdU injection after a survival time (ST) of 14 h labeled about 100 nuclei in the lateral soma clusters (LC), comprised of projection neurons, and about 30 nuclei in the medial soma clusters (MC), comprised of local interneurons. The BrdU-positive nuclei were confined to small regions at the inside of these clusters, which also contain nuclei in different phases of mitosis and thus represent proliferative zones. After STs of 2 weeks or 3 months, the number of BrdU-positive nuclei was doubled, indicating a mitosis of all originally labeled cells. Dependent on ST, the BrdU-positive nuclei were translocated from the proliferative zones towards the outside of the clusters, where somata of mature neurons reside. Immunostainings with antibodies to the neuropeptides FMRFamide and substance P, both of which label a large portion of somata in the MC and a pair of giant neurons projecting into the LC, revealed that in both clusters the proliferative zones are surrounded by, but are themselves devoid of, labeling. In the MC, some BrdU-positive somata were double-labeled by the FMRFamide antibody after an ST of 3 months, and by the substance P antibody after STs of 6 and 11/14 months, but not after 3 months. In the LC, BrdU-positive somata after an ST of 3 months partially and after 6 and 11/14 months widely overlapped with the arborizations of the giant neurons, indicating the establishment of synaptic input. The experiments show that cells generated in proliferative zones in the LC and MC of adult spiny lobsters after a final mitosis differentiate into neurons within months, survive for at least 1 year, and are integrated into the circuitry of the olfactory midbrain. A new hypothesis about the mechanism of adult neurogenesis in the central olfactory pathway of decapod crustaceans is developed, linking it to neurogenesis during embryonic and larval development. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 181,203, 2001 [source] A direct main olfactory bulb projection to the ,vomeronasal' amygdala in female mice selectively responds to volatile pheromones from malesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2009Ningdong Kang Abstract The main olfactory system, like the accessory olfactory system, responds to pheromones involved in social communication. Whereas pheromones detected by the accessory system are transmitted to the hypothalamus via the medial (,vomeronasal') amygdala, the pathway by which pheromones are detected and transmitted by the main system is not well understood. We examined in female mice whether a direct projection from mitral/tufted (M/T) cells in the main olfactory bulb (MOB) to the medial amygdala exists, and whether medial amygdala-projecting M/T cells are activated by volatile urinary odors from conspecifics or a predator (cat). Simultaneous anterograde tracing using Phaseolus vulgaris leucoagglutinin and Fluoro-Ruby placed in the MOB and accessory olfactory bulb (AOB), respectively, revealed that axons of MOB M/T cells projected to superficial laminae of layer Ia in anterior and posterodorsal subdivisions of the medial amygdala, whereas projection neurons from the AOB sent axons to non-overlapping, deeper layer Ia laminae of the same subdivisions. Placement of the retrograde tracer cholera toxin B into the medial amygdala labeled M/T cells that were concentrated in the ventral MOB. Urinary volatiles from male mice, but not from female conspecifics or cat, induced Fos in medial amygdala-projecting MOB M/T cells of female subjects, suggesting that information about male odors is transmitted directly from the MOB to the ,vomeronasal' amygdala. The presence of a direct MOB-to-medial amygdala pathway in mice and other mammals could enable volatile, opposite-sex pheromones to gain privileged access to diencephalic structures that control mate recognition and reproduction. [source] The type 1 cannabinoid receptor is highly expressed in embryonic cortical projection neurons and negatively regulates neurite growth in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2008Tania Vitalis Abstract In the rodent and human embryonic brains, the cerebral cortex and hippocampus transiently express high levels of type 1 cannabinoid receptors (CB1Rs), at a developmental stage when these areas are composed mainly of glutamatergic neurons. However, the precise cellular and subcellular localization of CB1R expression as well as effects of CB1R modulation in this cell population remain largely unknown. We report that, starting from embryonic day 12.5, CB1Rs are strongly expressed in both reelin-expressing Cajal-Retzius cells and newly differentiated postmitotic glutamatergic neurons of the mouse telencephalon. CB1R protein is localized first to somato-dendritic endosomes and at later developmental stages it localizes mostly to developing axons. In young axons, CB1Rs are localized both to the axolemma and to large, often multivesicular endosomes. Acute maternal injection of agonist CP-55940 results in the relocation of receptors from axons to somato-dendritic endosomes, indicating the functional competence of embryonic CB1Rs. The adult phenotype of CB1R expression is established around postnatal day 5. By using pharmacological and mutational modulation of CB1R activity in isolated cultured rat hippocampal neurons, we also show that basal activation of CB1R acts as a negative regulatory signal for dendritogenesis, dendritic and axonal outgrowth, and branching. Together, the overall negative regulatory role in neurite development suggests that embryonic CB1R signaling may participate in the correct establishment of neuronal connectivity and suggests a possible mechanism for the development of reported glutamatergic dysfunction in the offspring following maternal cannabis consumption. [source] Striatal modulation of cAMP-response-element-binding protein (CREB) after excitotoxic lesions: implications with neuronal vulnerability in Huntington's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2006Carmela Giampŕ Abstract Recent evidence has shown that the activity of cAMP responsive element-binding protein (CREB) and of CREB-binding protein (CBP) is decreased in Huntington's disease (HD) [Steffan et al. (2000)Proc. Natl Acad. Sci. USA, 97, 6763,6768; Gines et al. (2003)Hum. Mol. Genet., 12, 497,508; Rouaux et al. (2004) Biochem. Pharmacol., 68, 1157,1164; Sugars et al. (2004)J. Biol. Chem., 279, 4988,4999]. Such decrease is thought to reflect the impaired energy metabolism observed in a HD mouse model, where a decline in striatum cAMP levels has been observed [Gines et al. (2003)Hum. Mol. Genet., 12, 497,508]. Increased levels of CREB have also been demonstrated to exert neuroprotective functions [Lonze & Ginty (2002)Neuron, 35, 605,623; Lonze et al. (2002)Neuron, 34, 371,385]. Our study aimed to investigate the distribution of CREB in the neuronal subpopulations of the striatum in normal rats compared to the HD model of quinolinic acid lesion. Twenty-five Wistar rats were administered quinolinic acid 100 mm into the right striatum, and killed after 24 h, 48 h, 1 week, 2 weeks, and six weeks, respectively. The contralateral striata were used as controls. Dual-label immunofluorescence was employed using antibodies against phosphorylated CREB and each of the different neuronal subpopulations markers. Our results show that activated CREB levels decrease progressively in projection neurons and parvalbumin (PARV) and calretinin (CALR) interneurons, whereas such levels remain stable in cholinergic and somatostatin interneurons. Thus, we speculate that the ability of cholinergic interneurons to maintain their levels of CREB after excitotoxic lesions is one of the factors determining their protection in Huntington's disease. [source] Transient maternal hypothyroxinemia at onset of corticogenesis alters tangential migration of medial ganglionic eminence-derived neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2005Estela Cuevas Abstract Correct positioning of cortical neurons during development depends on the radial migration of the projection neurons and on the coordinated tangential and radial migrations of the subcortically generated interneurons. As previously shown, a transient and moderate maternal deficiency in thyroxin during early corticogenesis alters the radial migration of projection neurons. To determine if a similar effect might also affect tangential migration of medial ganglionic eminence (MGE)-derived neurons at the origin of cortical interneurons, explants of MGE from green fluorescent protein (GFP)-transgenic embryos were implanted into flat cortical mounts from wild-type embryos. The distances covered and the preferential migration (medially) of GFP-MGE neurons from embryos of hypothyroxinemic dams are not affected in their tangential migration into wild-type control cortices. In contrast, when GFP-MGE neurons from embryos of control or hypothyroxinemic dams migrate within cortices from embryos of hypothyroxinemic dams, the GFP-MGE-derived neurons lose their preferential direction of migration, although they still migrate for long distances throughout the cortex. Our results show that maternal hypothyroxinemia alters the tangential migration of GFP-MGE-derived neurons in the neocortex of the progeny and suggest that this alteration is not derived from the migratory neurons themselves but through undefined short- and long-range cues responsible for the guidance of their migration. [source] Demonstration of long-range GABAergic connections distributed throughout the mouse neocortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2005Ryohei Tomioka Abstract ,-Aminobutyric acid (GABA)ergic neurons in the neocortex have been mainly regarded as interneurons and thought to provide local interactions. Recently, however, glutamate decarboxylase (GAD) immunocytochemistry combined with retrograde labeling experiments revealed the existence of GABAergic projection neurons in the neocortex. We further studied the network of GABAergic projection neurons in the neocortex by using GAD67-green fluorescent protein (GFP) knock-in mice for retrograde labeling and a novel neocortical GABAergic neuron labeling method for axon tracing. Many GFP-positive neurons were retrogradely labeled after Fast Blue injection into the primary somatosensory, motor and visual cortices. These neurons were labeled not only around the injection site, but also at a long distance from the injection site. Of the retrogradely labeled GABAergic neurons remote from the injection sites, the vast majority (91%) exhibited somatostatin immunoreactivity, and were preferentially distributed in layer II, layer VI and in the white matter. In addition, most of GABAergic projection neurons were positive for neuropeptide Y (82%) and neuronal nitric oxide synthase (71%). We confirmed the long-range projections by tracing GFP-labeled GABAergic neurons with axon branches traveled rostro-caudally and medio-laterally. Axon branches could be traced up to 2 mm. Some (n = 2 of 4) were shown to cross the areal boundaries. The GABAergic projection neurons preferentially received neocortical inputs. From these results, we conclude that GABAergic projection neurons are distributed throughout the neocortex and are part of a corticocortical network. [source] Inhibition of superior colliculus neurons by a GABAergic input from the pretectal nuclear complex in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2004Gesche Born Abstract The mammalian pretectal nuclear complex (PNC) is a visual and visuomotor control structure which is strongly connected to other subcortical visual structures. This indicates that the PNC also controls subcortical visual information flow during the execution of various oculomotor programs. A prominent, presumably GABAergic, projection from the PNC targets the superficial grey layer of the superior colliculus (SC), which itself is a central structure for visual information processing necessary for the generation of saccadic eye movements. In order to characterize the pretecto-tectal projection in vitro, we performed whole-cell patch-clamp recordings from SC and PNC neurons in slices obtained from 3,6-week-old pigmented rats. Focal glutamate injections into the PNC and electrical PNC stimulation were used to induce postsynaptic responses in SC neurons. Electrical stimulation of the SC allowed electrophysiological identification of PNC neurons that provide the inhibitory pretecto-tectal input. Only inhibitory postsynaptic currents could be elicited in SC neurons both by pharmacological and by electrical activation of the ipsilateral PNC. Concomitantly, a small number of PNC neurons could be antidromically activated from the ipsilateral SC. Most SC cells postsynaptic to the prectectal input showed the dendritic morphology of wide-field and narrow-field cells and are therefore regarded as projection neurons. All inhibitory currents evoked by PNC activation could be completely blocked by bath application of the selective GABAA receptor antagonist bicuculline. Together these results indicate that SC projection neurons receive a direct inhibitory input from the ipsilateral PNC and that this input is mediated by GABAA receptors. [source] Presynaptic muscarinic acetylcholine receptors suppress GABAergic synaptic transmission in the intermediate grey layer of mouse superior colliculusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2004Fengxia Li Abstract The intermediate grey layer (the stratum griseum intermediale; SGI) of the superior colliculus (SC) receives cholinergic inputs from the parabrachial region of the brainstem. It has been shown that cholinergic inputs activate nicotinic acetylcholine (nACh) receptors on projection neurons in the SGI. Therefore, it has been suggested that they facilitate the initiation of orienting behaviours. In this study, we investigated the effect of muscarinic acetylcholine (mACh) receptor activation on GABAergic synaptic transmission to SGI neurons using the whole-cell patch-clamp recording technique in slice preparations from mice. The GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) evoked in SGI neurons by focal electrical stimulation were suppressed by bath application of 10 µm muscarine chloride. During muscarine application, both the paired-pulse facilitation index and the coefficient of variation of IPSCs increased; however, the current responses induced by a transient pressure application of 1 mm GABA were not affected by muscarine. Muscarine reduced frequencies of miniature IPSCs (mIPSCs) while the amplitudes of mIPSCs remained unchanged. These results suggestd that mAChR-mediated inhibition of IPSCs was of presynaptic origin. The suppressant effect of muscarine was antagonized by an M1 receptor antagonist, pirenzepine dihydrochloride (1 µm), and a relatively specific M3 receptor antagonist, 4-DAMP methiodide (50 nm). By contrast, an M2 receptor antagonist, methoctramine tetrahydrochloride (10 µm), was ineffective. These results suggest that the cholinergic inputs suppress GABAergic synaptic transmission to the SGI neurons at the presynaptic site via activation of M1 and, possibly, M3 receptors. This may be an additional mechanism by which cholinergic inputs can facilitate tectofugal command generation. [source] The subcellular localization of GABAB receptor subunits in the rat substantia nigraEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2003Justin Boyes Abstract The inhibitory effects of GABA within the substantia nigra (SN) are mediated in part by metabotropic GABAB receptors. To better understand the mechanisms underlying these effects, we have examined the subcellular localization of the GABAB receptor subunits, GABAB1 and GABAB2, in SN neurons and afferents using pre-embedding immunocytochemistry combined with anterograde or retrograde labelling. In both the SN pars compacta (SNc) and pars reticulata (SNr), GABAB1 and GABAB2 showed overlapping, but distinct, patterns of immunolabelling. GABAB1 was more strongly expressed by putative dopaminergic neurons in the SNc than by SNr projection neurons, whereas GABAB2 was mainly expressed in the neuropil of both regions. Immunogold labelling for GABAB1 and GABAB2 was localized in presynaptic and postsynaptic elements throughout the SN. The majority of labelling was intracellular or was associated with extrasynaptic sites on the plasma membrane. In addition, labelling for both subunits was found on the presynaptic and postsynaptic membranes at symmetric, putative GABAergic synapses, including those formed by anterogradely labelled striatonigral and pallidonigral terminals. Labelling was also observed on the presynaptic membrane and at the edge of the postsynaptic density at asymmetric, putative excitatory synapses. Double immunolabelling, using the vesicular glutamate transporter 2, revealed the glutamatergic nature of many of the immunogold-labelled asymmetric synapses. The widespread distribution of GABAB subunits in the SNc and SNr suggests that GABAB -mediated effects in these regions are likely to be more complex than previously described, involving presynaptic autoreceptors and heteroreceptors, and postsynaptic receptors on different populations of SN neurons. [source] Synaptic and non-synaptic mechanisms of amygdala recruitment into temporolimbic epileptiform activitiesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2003Julia Klueva Abstract Lateral amygdala (LA) activity during synchronized-epileptiform discharges in temporolimbic circuits was investigated in rat horizontal slices containing the amygdala, hippocampus (Hip), perirhinal (Prh) and lateral entorhinal (LEnt) cortex, through multiple-site extra- and intracellular recording techniques and measurement of the extracellular K+ concentration. Application of 4-aminopyridine (50 µm) induced epileptiform discharges in all regions under study. Slow interictal-like burst discharges persisted in the Prh/LEnt/LA after disconnection of the Hip, seemed to originate in the Prh as shown from time delay analyses, and often preceded the onset of ictal-like activity. Disconnection of the amygdala resulted in de-synchronization of epileptiform discharges in the LA from those in the Prh/LEnt. Interictal-like activity was intracellularly reflected in LA projection neurons as ,-aminobutyric acid (GABA)A/B receptor-mediated synaptic responses, and depolarizing electrogenic events (spikelets) residing on the initial phase of the GABA response. Spikelets were considered antidromically conducted ectopic action potentials generated at axon terminals, as they were graded in amplitude, were not abolished through hyperpolarizing membrane responses (which effectively blocked evoked orthodromic action potentials), lacked a clear prepotential or synaptic potential, were not affected through blockers of gap junctions, and were blocked through remote application of tetrodotoxin at putative target areas of LA projection neurons. Remote application of a GABAB receptor antagonist facilitated spikelet generation. A transient elevation in the extracellular K+ level averaging 3 mm above baseline occurred in conjunction with interictal-like activity in all areas under study. We conclude that interictal-like discharges in the LA/LEnt/Prh spread in a predictable manner through the synaptic network with the Prh playing a leading role. The rise in extracellular K+ may provide a depolarizing mechanism for recruitment of interneurons and generation of ectopic action potentials at axon terminals of LA projection neurons. Antidromically conducted ectopic action potentials may provide a spreading mechanism of seizure activity mediated by diffuse axonal projections of LA neurons. [source] Postnatal maturation of GABAA and GABAC receptor function in the mammalian superior colliculusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2001Mathias Boller Abstract In the stratum griseum superficiale (SGS) of the mammalian superior colliculus, GABAC receptors seem to control the excitability of projection neurons by selective inactivation of local GABAergic interneurons. As the onset of visual responses to SC begins well after birth in the rat, it is possible to study developmental changes in GABAergic mechanisms that are linked to the onset of visual information processing. In order to analyse postnatal changes in inhibitory mechanisms that involve GABA receptor function, we used extracellular field potential (FP) recordings and single cell patch-clamp techniques in slices from postnatal day 4 (P4) to P32 and examined the effects of GABA and muscimol on electrically evoked SGS cell activity. While GABAA receptor activation affected FP amplitudes throughout postnatal development, GABAC receptor activation did not significantly change FP amplitudes until the third postnatal week. Results from patch-clamping single cells, however, clearly demonstrate that GABAC receptors are already functional at P4 , similar to GABAA receptors. Throughout postnatal development, activation of GABAC receptors leads to a strong inhibition of inhibitory postsynaptic activity, indicating that GABAC receptors are expressed by inhibitory interneurons. Furthermore, the proportion of neurons that show decreased excitatory postsynaptic activity during GABAC receptor activation correlates with the proportion of GABAergic interneurons in SGS. Our patch-clamp results indicate that the functional expression of GABAC receptors by GABAergic interneurons does not change significantly during postnatal development. However, our measurements of FP amplitudes indicate that the maturation of the efferent connections of these GABAergic neurons within SGS during the third postnatal week strongly changes GABAC receptor function. [source] Inhibition of scratching behaviour caused by contact dermatitis in histidine decarboxylase gene knockout miceEXPERIMENTAL DERMATOLOGY, Issue 3 2005M. Seike Abstract:, A neuronal system dedicated to itch consists of primary afferent and spinothalamic projection neurons. Histamine is thought to be one of the main mediators for the transmission of itch sensation. However, there are little available information on the role of histamine in scratching behaviour and sensory transmission of atopic dermatitis and chronic eczema. In the present study, the role of histamine in scratching behaviour and neural conduction of sensation in the chronic eczema model was investigated by using l-histidine decarboxylase (HDC) gene knockout mice lacking histamine. The chronic contact dermatitis was induced with daily application of diphenylcyclopropenone (DCP) on a hind paw of HDC (+/+) and HDC (,/,) mice for 2 months. The observation of scratching behaviour and the hot-plate test were performed in both mice. Histological studies were performed in the skin and spinal cord tissues. Histological examination revealed that both HDC (+/+) and HDC (,/,) mice displayed the similar extent of inflammatory cell infiltration, hyperplastic epidermis and newly spreading of neuronal processes in the skin tissue. Scratching behaviour was exclusively induced in HDC (+/+) mice, whereas it was barely observed in HDC (,/,) mice. The expression of c-Fos was specifically upregulated in HDC (+/+) mice in lamina I of the spinal dorsal horn following repeated DCP application. Scratching behaviour in chronic contact dermatitis in mice was thought mainly mediated with histamine. The afferent pathway of sensation in chronic contact dermatitis model may connect with the central nervous system through lamina I of the spinal dorsal horn. [source] Axonal integrity in the absence of functional peroxisomes from projection neurons and astrocytesGLIA, Issue 13 2010Astrid Bottelbergs Abstract Ablation of functional peroxisomes from all neural cells in Nestin-Pex5 knockout mice caused remarkable neurological abnormalities including motoric and cognitive malfunctioning accompanied by demyelination, axonal degeneration, and gliosis. An oligodendrocyte selective Cnp-Pex5 knockout mouse model shows a similar pathology, but with later onset and slower progression. Until now, the link between these neurological anomalies and the known metabolic alterations, namely the accumulation of very long-chain fatty acids (VLCFA) and reduction of plasmalogens, has not been established. We now focused on the role of peroxisomes in neurons and astrocytes. A neuron-specific peroxisome knockout model, NEX-Pex5, showed neither microscopic nor metabolic abnormalities indicating that the lack of functional peroxisomes within neurons does not cause axonal damage. Axonal integrity and normal behavior was also preserved when peroxisomes were deleted from astrocytes in GFAP-Pex5,/, mice. Nevertheless, peroxisomal metabolites were dysregulated in brain including a marked accumulation of VLCFA and a slight reduction in plasmalogens. Interestingly, despite minor targeting of oligodendrocytes in GFAP-Pex5,/, mice, these metabolic perturbations were also present in isolated myelin indicating that peroxisomal metabolites are shuttled between different brain cell types. We conclude that absence of peroxisomal metabolism in neurons and astrocytes does not provoke the neurodegenerative phenotype observed after deleting peroxisomes from oligodendrocytes. Lack of peroxisomal metabolism in astrocytes causes increased VLCFA levels in myelin, but this has no major impact on neurological functioning. © 2010 Wiley-Liss, Inc. [source] Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: Relevance for Huntington's diseaseGLIA, Issue 11 2009Onintza Sagredo Abstract Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington's disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed by using the selective CB2 receptor antagonist, SR144528, and by the observation that mice deficient in CB2 receptor were more sensitive to malonate than wild-type animals. CB2 receptors are scarce in the striatum in healthy conditions, but they are markedly upregulated after the lesion with malonate. Studies of double immunostaining revealed a significant presence of CB2 receptors in cells labeled with the marker of reactive microglia OX-42, and also in cells labeled with GFAP (a marker of astrocytes). We further showed that the activation of CB2 receptors significantly reduced the levels of tumor necrosis factor-, (TNF-,) that had been increased by the lesion with malonate. In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be upregulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-,. Altogether, our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD. © 2008 Wiley-Liss, Inc. [source] Interleukin 15 expression in the CNS: Blockade of its activity prevents glial activation after an inflammatory injuryGLIA, Issue 5 2008Diego Gómez-Nicola Abstract Although reactive glia formation after neuronal degeneration or traumatic damage is one of the hallmarks of central nervous system (CNS) injury, we have little information on the signals that direct activation of resting glia. IL-15, a pro-inflammatory cytokine involved in regulating the response of T and B cells, may be also key for the regulation of early inflammatory events in the nervous system. IL-15 was expressed in the CNS, most abundantly in cerebellum and hippocampus, mainly in astrocytes and in some projection neurons. Using a rodent model of acute inflammatory injury [lipopolysaccharide (LPS) injection], we found enhanced expression of IL-15 in both reactive astroglia and microglia, soon after CNS injury. Blockade of IL-15 activity with an antibody to the cytokine, reversed activation of both glial types, suggesting that IL-15 has a major role in the generation of gliotic tissue and in the regulation of neuroimmune responses. Because IL-15 appears to modulate the inflammatory environment acutely generated after CNS injury, regulating IL-15 expression seems a clear antiinflammatory therapy to improve the outcome of neurodegenerative diseases and CNS trauma. © 2008 Wiley-Liss, Inc. [source] Profiling of neuropeptides released at the stomatogastric ganglion of the crab, Cancer borealis with mass spectrometryJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Cyrus P. Billimoria Abstract Studies of release under physiological conditions provide more direct data about the identity of neuromodulatory signaling molecules than studies of tissue localization that cannot distinguish between processing precursors and biologically active neuropeptides. We have identified neuropeptides released by electrical stimulation of nerves that contain the axons of the modulatory projection neurons to the stomatogastric ganglion of the crab, Cancer borealis. Preparations were bathed in saline containing a cocktail of peptidase inhibitors to minimize peptide degradation. Both electrical stimulation of projection nerves and depolarization with high K+ saline were used to evoke release. Releasates were desalted and then identified by mass using MALDI,TOF (matrix-assisted laser desorption/ionization,time-of-flight) mass spectrometry. Both previously known and novel peptides were detected. Subsequent to electrical stimulation proctolin, Cancer borealis tachykinin-related peptide (CabTRP), FVNSRYa, carcinustatin-8, allatostatin-3 (AST-3), red pigment concentrating hormone, NRNFLRFa, AST-5, SGFYANRYa, TNRNFLRFa, AST-9, orcomyotropin-related peptide, corazonin, Ala13-orcokinin, and Ser9-Val13-orcokinin were detected. Some of these were also detected after high K+ depolarization. Release was calcium dependent. In summary, we have shown release of the neuropeptides thought to play an important neuromodulatory role in the stomatogastric ganglion, as well as numerous other candidate neuromodulators that remain to be identified. [source] Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5 Prevent the Death of Striatal Projection Neurons in a Rodent Model of Huntington's DiseaseJOURNAL OF NEUROCHEMISTRY, Issue 5 2000Esther Pérez-Navarro Abstract: Intrastriatal injection of quinolinate has been proven to be a very useful animal model to study the pathogenesis and treatment of Huntington's disease. To determine whether growth factors of the neurotrophin family are able to prevent the degeneration of striatal projection neurons, cell lines expressing brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) were grafted in the adult rat striatum before quinolinate injection. Three days after lesioning, ongoing cell death was assessed by in situ detection of DNA fragmentation. In animals grafted with the control cell line, quinolinate injection induced a gradual cell loss that was differentially prevented by intrastriatal grafting of BDNF-, NT-3-, or NT-4/5-secreting cells. Seven days after lesioning, we characterized striatal projection neurons that were protected by neurotrophins. Quinolinate injection, alone or in combination with the control cell line, induced a selective loss of striatal projection neurons. Grafting of a BDNF-secreting cell line prevented the loss of all types of striatal projection neurons analyzed. Glutamic acid decarboxylase 67-, preproenkephalin-, and preprotachykinin A- but not prodynorphin-expressing neurons were protected by grafting of NT-3- or NT-4/5-secreting cells but with less efficiency than the BDNF-secreting cells. Our findings show that neurotrophins are able to promote the survival of striatal projection neurons in vivo and suggest that BDNF might be beneficial for the treatment of striatonigral degenerative disorders, including Huntington's disease. [source] Alcohol Inhibits Spontaneous Activity of Basolateral Amygdala Projection Neurons in the Rat: Involvement of the Endocannabinoid SystemALCOHOLISM, Issue 3 2008Simona Perra Background:, A large body of evidence indicates that the limbic system is involved in the neural processing underlying drug addiction. Among limbic regions, the basolateral nucleus of amygdala (BLA) is implicated in some aspects of the neurobiological mechanisms of drugs of abuse, including alcohol and cannabinoids. It is recently emerging that the endocannabinoid system is involved in many pharmacological and behavioral effects of alcohol. The BLA possesses a very high density of CB1 cannabinoid receptors, and endocannabinoids modulate forms of synaptic plasticity in this region. The aims of our study were first to investigate in vivo the sensitivity of BLA pyramidal neurons to alcohol and second to determine the role of the endocannabinoid system in the acute effects of alcohol. Methods:, We utilized extracellular single cell recordings in urethane anesthetized rats from BLA principal neurons, antidromically identified from their projection site in the nucleus accumbens. Results:, Alcohol (0.25 to 2.0 g/kg i.v.) induced a marked decrease in the spontaneous firing rate of BLA projecting neurons (51.1 ± 16% of baseline at 0.5 g/kg alcohol, p < 0.0001). The involvement of the endogenous cannabinoid system was investigated by administering the CB1 receptor antagonist SR141716A (rimonabant, SR) (1.0 mg/kg i.v.) before alcohol. SR per se did not significantly affect firing rate of BLA neurons, but it prevented the inhibition produced by alcohol (98 ± 18% of baseline firing at 0.5 g/kg alcohol, p < 0.01). Then, we studied the actions of alcohol following a chronic treatment with the CB1 agonist WIN55212-2 (WIN). Animals were administered WIN for 6.5 days (2.0 mg/kg, i.p. twice daily) and alcohol dose,response curves were carried out on firing rate of BLA neurons 24 hours following the last injection of the cannabinoid agonist. In WIN-treated animals the inhibitory effect of alcohol was significantly reduced as compared with controls (95 ± 16% of baseline firing at 0.5 g/kg, p < 0.05). Conclusions:, Our results provide evidence of the involvement of the endocannabinoid system in the effects of alcohol on BLA projection neurons. They also further point to the endocannabinoid system as a possible molecular target in the treatment of alcoholism. [source] 14-3-3 protein in the CSF of inflammatory peripheral neuropathiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004A Bersano 14-3-3 proteins are a highly conserved protein family of unknown function, although some authors suggested a role in cellular proliferation and differentiation, neurotransmitters biosynthesis and apoptosis. The expression of these proteins increases during development, in particular, in large projection neurons such as spinal motor neurons. Recently the protein was described in cerebrospinal fluid (CSF) of patients with spongiform encephalopathies, in particular Creutzfeld-Jacob disease, where the protein is considered a highly sensitive and specific marker. 14-3-3 protein has been also detected in CSF of other prion-unrelated dementias and other neurodegenerative (Parkinson disease, stroke and paraneoplastic syndromes) and inflammatory diseases like Multiple Sclerosis. The aim of our study was to evaluate whether the 14-3-3 protein is also present in the CSF of peripheral nervous system diseases. We studied by Western Blot the CSF of 120 patients including 38 with Guillain-Barré syndrome (GBS), 23 with chronic inflammatory demyelinating polyneuropathy (CIDP), 12 with multifocal motor neuropathies (MMN), 20 motor neuron disease (MND), 8 paraneoplastic syndrome, 14 other neuropathies or radiculopathies (OPN), and 5 normal subjects (NC). We found the 14-3-3 protein in the CSF of 21 (55%) patients with GBS, 13 (56%) with CIDP, 1 (5%) with MND, 3 (21%) with OPN and none with paraneoplastic syndrome, MMN or NC. Our results reveal that 14-3-3 protein can be detected not only in central but also in peripheral nervous system diseases where it is significantly associated (p < 0.0001) with GBS and CIDP. [source] Motor thalamic circuits in primates with emphasis on the area targeted in treatment of movement disordersMOVEMENT DISORDERS, Issue S3 2002Igor A. Ilinsky MD Abstract The ventral region of the motor thalamus that receives cerebellar afferents has been and still is the target of stereotactic interventions for movement disorders. According to Hassler, this area includes ventro-oralis posterior (Vop) and ventral intermedius (Vim) nuclei, although some investigators believe that Vop is associated with the pallidothalamic pathway. We sought to correlate our experimental data on distribution of nigral, pallidal, and cerebellar afferents to the monkey thalamus with Hassler's motor thalamic parcelations. We concluded that Hassler's parcelations retained their value, although some adjustments were needed to relate them to the current neuroanatomic data; particularly, the cerebellothalamic zone that represents the monkey ventral lateral nucleus (VL) corresponds topographically to Hassler's Vop, Vim, and most of Voi. Electron microscopic tracing studies have shown very complex circuitry in this region of the monkey thalamus, as the cerebellar and cortical afferents innervating it are engaged in complex synapses with thalamocortical projection neurons, and this interaction is strongly modulated by local circuit neurons and the input from the reticular thalamic nucleus, which are both inhibitory and ,-aminobutyric acid (GABA)ergic. Spinothalamic afferents also reach the VL, but this input is less studied in the monkey. The circuitry subserving the activity of thalamocortical projection neurons in the VL should be considered while interpreting the functional data obtained in stereotactic surgery. © 2002 Movement Disorder Society [source] Axonal branching patterns of nucleus accumbens neurons in the ratTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 22 2010Anushree Tripathi Abstract The patterns of axonal collateralization of nucleus accumbens (Acb) projection neurons were investigated in the rat by means of single-axon tracing techniques using the anterograde tracer biotinylated dextran amine. Seventy-three axons were fully traced, originating from either the core (AcbC) or shell (AcbSh) compartment, as assessed by differential calbindin D28k-immunoreactivity. Axons from AcbC and AcbSh showed a substantial segregation in their targets; target areas were either exclusively or preferentially innervated from AcbC or AcbSh. Axon collaterals in the subthalamic nucleus were found at higher than expected frequencies; moreover, these originated exclusively in the dorsal AcbC. Intercompartmental collaterals were observed from ventral AcbC axons into AcbSh, and likewise, interconnections at pallidal and mesencephalic levels were also observed, although mostly from AcbC axons toward AcbSh targets, possibly supporting crosstalk between the two subcircuits at several levels. Cell somata giving rise to short-range accumbal axons, projecting to the ventral pallidum (VP), were spatially intermingled with others, giving rise to long-range axons that innervated VP and more caudal targets. This anatomical organization parallels that of the dorsal striatum and provides the basis for possible dual direct and indirect actions from a single axon on either individual or small sets of neurons. J. Comp. Neurol. 518:4649,4673, 2010. © 2010 Wiley-Liss, Inc. [source] | |||||||||||||