Abstract
This study aimed at providing the first detailed morphological description, at the single-cell level, of the rat dorsal raphe nucleus neurons, including the distribution of the VGLUT3 protein within their axons. Electrophysiological guidance procedures were used to label dorsal raphe nucleus neurons with biotinylated dextran amine. The somatodendritic and axonal arborization domains of labeled neurons were reconstructed entirely from serial sagittal sections using a computerized image analysis system. Under anaesthesia, dorsal raphe nucleus neurons display highly regular (1.72±0.50 Hz) spontaneous firing patterns. They have a medium size cell body (9.8±1.7 µm) with 2–4 primary dendrites mainly oriented anteroposteriorly. The ascending axons of dorsal raphe nucleus are all highly collateralized and widely distributed (total axonal length up to 18.7 cm), so that they can contact, in various combinations, forebrain structures as diverse as the striatum, the prefrontal cortex and the amygdala. Their morphological features and VGLUT3 content vary significantly according to their target sites. For example, high-resolution confocal analysis of the distribution of VGLUT3 within individually labeled-axons reveals that serotonin axon varicosities displaying VGLUT3 are larger (0.74±0.03 µm) than those devoid of this protein (0.55±0.03 µm). Furthermore, the percentage of axon varicosities that contain VGLUT3 is higher in the striatum (93%) than in the motor cortex (75%), suggesting that a complex trafficking mechanism of the VGLUT3 protein is at play within highly collateralized axons of the dorsal raphe nucleus neurons. Our results provide the first direct evidence that the dorsal raphe nucleus ascending projections are composed of widely distributed neuronal systems, whose capacity to co-release serotonin and glutamate varies from one forebrain locus to the other.
Highlights
Neurons of the raphe nuclei are involved in multitudinous functions, such as the regulation of sleep-waking cycle, the modulation of pain signals and the pathogenesis of mood disorders
Most injection loci display a dense core of biotin dextran amine (BDA) precipitate surrounded by several neurons labeled in a Golgi-like manner (Fig. 1A)
Our confocal immunofluorescence analysis has provided the first demonstration of the precise distribution of vesicular glutamate transporter 3 (VGLUT3), vesicular monoamine transporter type 2 (VMAT2), 5-HT and SERT in singlylabeled DRN neurons
Summary
Neurons of the raphe nuclei are involved in multitudinous functions, such as the regulation of sleep-waking cycle, the modulation of pain signals and the pathogenesis of mood disorders. This multifaceted role of raphe neurons is possible because they form a widely distributed neuronal system that reaches virtually all major brain structures, as indicated by previous immunolabeling studies [1]. Bulk injections of anterograde tracers have revealed that the dorsal raphe efferent projections are widely distributed [13,14,15,16] This notion was further extended by antidromic invasion experiments [17]. Similar approach was used to gather morphological data on 5-HT neurons of the rat medulla [20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
