A combined electron microscopic HRP and immunocytochemical study of the limbic projections to rat hypothalamic nuclei containing vasopressin and oxytocin neurons

Abstract

Light microscopic studies in our laboratory have indicated that the lateral septum, amygdala, and ventral subiculum project in a perinuclear fashion to the paraventricular (PVN), supraoptic (SON), and suprachiasmatic (SCN) nuclei (Oldfield et al., '82; Silverman and Oldfield, '84). In the present paper a combined anterograde HRP and immunocytochemical procedure has been used to determine the connectivity between these limbic efferents and peptide-containing processes emanating from the above mentioned hypothalamic nuclei. Synaptic associations were found to exist between efferents from (1) the septum and both vasopressin (VP)- and oxytocin (OX)-positive dendrites derived from cells in the PVN and SON, (2) the septum and VP dendrites dorsal to the SCN, (3) the ventral subiculum and both VP and OX dendrites arising from the PVN and SON, and (iv) the amygdala and VP dendrites from the PVN. These observations help clarify an apparent discrepancy between electrophysiological data, in which limbic efferents have been shown to influence the activity of VP and OX neurons in the PVN and SON, and anatomical evidence which indicates only a perinuclear innervation from these sites not encroaching on the hypothalamic nuclei themselves. In each case the synaptic connections are made on dendrites external to the nucleus: those lateral and ventrolateral to the PVN, dorsal to the SON, and dorsal or dorsolateral to the SCN.

Central afferent pathways conveying nociceptive input to the hypothalamic paraventricular nucleus as revealed by a combination of retrograde labeling and c-fos activation

“…Concerning the forebrain extrahypothalamic and hypothalamic nuclei, the distribution of retrograde labeling was rather similar to that depicted with FluoroGold by Cullinan et al (1996). Similar to what was reported in that study, labeling of the LS and Me was likely due to perinuclear CTb uptake, because such limbic structures have long been known to project to areas around the PVN (Oldfield et al, 1985). The inclusion of the lamina terminalis cell groups at the anteroventral tip of the third ventricle (i.e., the SFO, OVLT, and MnPO; Sawchenko et al, 1996) has been signaled recently by Larsen and Mikkelsen (1995), who used CTb retrograde labeling from the PVN to investigate the pathways involved in HPA responses to the intraperitoneal injection of hypertonic saline.…”

“…It is likely that the incompletely filled PVN divisions contained enough tracer for consistent CTb uptake. On the other hand, local neurons are known to have dendrites that invade the neighboring divisions or even the perinuclear region, as demonstrated with electron microscopy by Oldfield et al (1985). Concerning the forebrain extrahypothalamic and hypothalamic nuclei, the distribution of retrograde labeling was rather similar to that depicted with FluoroGold by Cullinan et al (1996).…”

Relaxin-3/RXFP3 signalling in mouse hypothalamus: no effect of RXFP3 activation on corticosterone, despite reduced presynaptic excitatory input onto paraventricular CRH neurons in vitro

“…However, as it appears from our studies that very few relaxin-3 immunoreactive fibres are present within the PVN proper, the source of endogenous relaxin-3 for the receptors may not be due to neuronal innervation, but rather alternative routes such as volume transmission through the CSF, facilitated by the close proximity of RXFP3-expressing neurons to the third ventricle (BorrotoEscuela et al 2015). The presence of a higher density of relaxin-3 positive fibres surrounding the PVN is also consistent with peptide diffusion, although it is also possible that synaptic transmission does occur at more distant nonsomatic contacts, as described for limbic inputs onto oxytocin/vasopressin neurons (Oldfield et al 1985). In the future, a better insight into the effects of RXFP3 activation on oxytocin/vasopressin neurons in the PVN could be obtained by conducting studies similar to our electrophysiology studies in equivalent oxytocin or vasopressin reporter mice or rats expressing a fluorophore in these cell types (Young et al 1999;Ueta et al 2005;Yoshikawa et al 2015).…”

Characterization of the Projections to the Hypothalamic Paraventricular and Periventricular Nuclei in the Female Sheep Brain, Using Retrograde Tracing and Immunohistochemistry

“…On the other hand, a high percentage of seretoninergic neurons in the raphe project to the PVN and the Pe in the ovine brain. Likewise, serotonergic cells of the dorsal raphe project to the PVN in the rat [114, 124] and these provide input to oxytocin- and vasopressin-producing neurons in the PVN [16, 75, 125] as well as stimulating corticotropin-releasing hormone gene expression [19, 75, 126] but similar studies are yet to be performed in the sheep. …”