Afferent projections to the rat locus coeruleus demonstrated by retrograde and anterograde tracing with cholera-toxin B subunit and Phaseolus vulgaris leucoagglutinin

Luppi, Pierre‐Hervé; Aston‐Jones, Gary; Akaoka, H.; Chouvet, Guy; Jouvet, Michel

doi:10.1016/0306-4522(94)00481-j

Cited by 311 publications

(275 citation statements)

References 59 publications

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“…15,16 Afferent projections from Ucn2-expressing nuclei to the DRN were shown in studies using both anterograde and retrograde tracers. [31][32][33][34] Thus, the expression of Ucn2 in known anatomical projections to the DRN suggests a possible role for Ucn2 in the functioning of 5-HT neurons during stress. Interestingly, detailed anatomical studies showed that Ucn3-expressing neurons do not innervate CRFR2-DRN neurons, 35 suggesting Ucn1 and Ucn2 as the endogenous ligands for CRFR2 activation in DRN neurons.…”

Section: Introductionmentioning

confidence: 99%

Urocortin-1 and -2 double-deficient mice show robust anxiolytic phenotype and modified serotonergic activity in anxiety circuits

et al. 2009

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The urocortin (Ucn) family of neuropeptides is suggested to be involved in homeostatic coping mechanisms of the central stress response through the activation of corticotropin-releasing factor receptor type 2 (CRFR2). The neuropeptides, Ucn1 and Ucn2, serve as endogenous ligands for the CRFR2, which is highly expressed by the dorsal raphe serotonergic neurons and is suggested to be involved in regulating major component of the central stress response. Here, we describe genetically modified mice in which both Ucn1 and Ucn2 are developmentally deleted. The double knockout mice showed a robust anxiolytic phenotype and altered hypothalamic-pituitary-adrenal axis activity compared with wild-type mice. The significant reduction in anxiety-like behavior observed in these mice was further enhanced after exposure to acute stress, and was correlated with the levels of serotonin and 5-hydroxyindoleacetic acid measured in brain regions associated with anxiety circuits. Thus, we propose that the Ucn/ CRFR2 serotonergic system has an important role in regulating homeostatic equilibrium under challenge conditions.

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Section: Introductionmentioning

confidence: 99%

Urocortin-1 and -2 double-deficient mice show robust anxiolytic phenotype and modified serotonergic activity in anxiety circuits

et al. 2009

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“…The burst-firing neurons were not observed in this group. addition, the lesion of 5-HT neurons with 5,7-dihydroxytryptamine increased the spontaneous firing activity of LC noradrenergic neurons [17] . Neurochemical and neuropathological studies have shown that 5-HT concentration is significantly reduced in the some areas of the brain and cerebrospinal fluid, and loss of 5-HT neurons in the raphe nuclei of Parkinsonian patients [18] .…”

Section: Resultsmentioning

confidence: 91%

Firing activity of locus coeruleus noradrenergic neurons increases in a rodent model of Parkinsonism

et al. 2009

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Objective To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD). Methods 2 and 4 weeks after unilateral lesion of the nigrostriatal pathway in the rat by local injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc), the firing activity of noradrenergic neurons in LC was recorded by extracellular single unit recording. Results The firing rate of LC noradrenergic neurons increased significantly 2 and 4 weeks after 6-OHDA lesions compared to normal rats, respectively (P < 0.05). The percentage of irregularly firing neurons was obviously higher than that of normal rats during the fourth week after SNc lesion (P < 0.05). Conclusion LC noradrenergic neurons are overactive and more irregular in 6-OHDA-lesioned rats. These changes suggest an implication of the LC in the pathophysiological mechanism of PD.

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“…The ribosome-inactivating protein, saporin (derived from seeds of the plant Saponaria officinalis), cannot be internalized by itself and therefore needs a targeting agent such as CTb. CTb binds to the GM1 ganglioside receptor that is present on most neuronal types and has proven to be a reliable neuronal tracer (Luppi et al, 1995;Ruigrok and Apps, 2007). After internalization and transport to the soma, saporin dissociates from the CTb and inactivates ribosomes, thereby eventually resulting in cell death.…”

Section: Neurotoxic Agentmentioning

confidence: 99%

Selective Impairment of the Cerebellar C1 Module Involved in Rat Hind Limb Control Reduces Step-Dependent Modulation of Cutaneous Reflexes

Pijpers¹,

Winkelman²,

Bronsing³

et al. 2008

J. Neurosci.

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The cerebellum is divided into multiple parasagittally organized modules, which are thought to represent functional entities. How individual modules participate in cerebellar control of complex movements such as locomotion remains largely unknown. To a large extent, this is caused by the inability to study the contribution of individual modules during locomotion. Because of the architecture of modules, based on narrow, elongated cortical strips that may be discontinuous in the rostrocaudal direction, lesion of a complete module, without affecting neighboring modules, has not been possible. Here, we report on a new method for inducing a selective dysfunction of spatially separated parts of a single module using a small cortical injection of a retrogradely transported neurotoxin, cholera toxin b-subunit-saporin. We show that such a local injection into the C1 module results in climbing fiber and partial mossy fiber deafferentation of functionally related areas of this module, thereby resulting in a severe impairment of the whole module without affecting neighboring modules. A subsequent functional analysis indicates that such an impairment of the hindlimb part of the C1 module did not have a significant impact on skilled walking or overall stepping pattern. However, the modulation of cutaneously induced reflexes during stepping was severely diminished. We propose that the C1 module is specifically involved in the adaptive control of reflexes.

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Afferent projections to the rat locus coeruleus demonstrated by retrograde and anterograde tracing with cholera-toxin B subunit and Phaseolus vulgaris leucoagglutinin

Cited by 311 publications

References 59 publications

Urocortin-1 and -2 double-deficient mice show robust anxiolytic phenotype and modified serotonergic activity in anxiety circuits

Urocortin-1 and -2 double-deficient mice show robust anxiolytic phenotype and modified serotonergic activity in anxiety circuits

Firing activity of locus coeruleus noradrenergic neurons increases in a rodent model of Parkinsonism

Selective Impairment of the Cerebellar C1 Module Involved in Rat Hind Limb Control Reduces Step-Dependent Modulation of Cutaneous Reflexes

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