The paraventricular nucleus of the hypothalamus (PVN) plays an essential role in the control of food intake and energy expenditure by integrating multiple neural and humoral inputs. Recent studies have demonstrated that intracerebroventricular and intra-PVN injections of the neuropeptide relaxin-3 or selective relaxin-3 receptor (RXFP3) agonists produce robust feeding in satiated rats, but the cellular and molecular mechanisms of action associated with these orexigenic effects have not been identified. In the present studies, using rat brain slices, we demonstrated that relaxin-3, acting through its cognate G-protein-coupled receptor, RXFP3, hyperpolarized a majority of putative magnocellular PVN neurons (88%, 22/25), including cells producing the anorexigenic neuropeptides, oxytocin and vasopressin. Importantly, the action of relaxin-3 persisted in the presence of tetrodotoxin and glutamate/GABA receptor antagonists, indicating its direct action on PVN neurons. Similar inhibitory effects on PVN oxytocin and vasopressin neurons were produced by the RXFP3 agonist, RXFP3-A2 (82%, 80/98 cells). In situ hybridization histochemistry revealed a strong colocalization of RXFP3 mRNA with oxytocin and vasopressin immunoreactivity in rat PVN neurons. A smaller percentage of putative parvocellular PVN neurons was sensitive to RXFP3-A2 (40%, 16/40 cells). These data, along with a demonstration of abundant peri-PVN and sparse intra-PVN relaxin-3-immunoreactive nerve fibres, originating from the nucleus incertus, the major source of relaxin-3 neurons, identify a strong inhibitory influence of relaxin-3-RXFP3 signalling on the electrical activity of PVN oxytocin and vasopressin neurons, consistent with the orexigenic effect of RXFP3 activation observed in vivo.
Our paper is the first to describe ultradian rhythmic neuronal oscillation in the intergeniculate leaflet (IGL) of the rat. We recorded a multiple-unit neuronal activity (MUA) from dorsal to ventral parts of the lateral geniculate nucleus (LGN) in anaesthetized rats. In all the subdivisions of the lateral geniculate complex we observed spontaneous irregular firing rates of cells. However only at the anatomical localisation of the IGL, after the light was on, those responses exhibited burst firing with a constant interburst interval, which lasted several hours until the light was off. The duration of that rhythmic oscillation obtained by means of Fourier's analysis was approximately 124 s. To date we have not had sufficient data to discuss possible mechanisms of this neuronal rhythmicity. We can only conclude that light is the most important stimulus not only for suprachiasmatic nuclei (SCN), but also for the IGL. On the other hand, we can neither exclude nor confirm that in order to evoke ultradian rhythmical oscillation in the IGL, in addition to light also non-photic information is necessary.
Behavioural state is controlled by a range of neural systems that are sensitive to internal and external stimuli. The relaxin-3 and relaxin family peptide receptor 3 (RXFP3) system has emerged as a putative ascending arousal network with putative involvement in regulation of stress responses, neuroendocrine control, feeding and metabolism, circadian activity and cognition. Relaxin-3/γ-aminobutyric acid neuron populations have been identified in the nucleus incertus, pontine raphe nucleus, periaqueductal grey (PAG) and an area dorsal to the substantia nigra. Relaxin-3-positive fibres/terminals densely innervate arousal-related structures in the brainstem, hypothalamus and limbic forebrain, but the functional significance of the heterogeneous relaxin-3 neuron distribution and its inputs to specific brain areas are unclear. Therefore, in this study, we used neuronal tract-tracing and immunofluorescence staining to explore the source of the dense relaxin-3 innervation of the intergeniculate leaflet (IGL) of the thalamus, a component of the neural circadian timing system. Confocal microscopy analysis revealed that relaxin-3-positive neurons retrogradely labelled from the IGL were predominantly present in the PAG and these neurons expressed corticotropin-releasing factor receptor-like immunoreactivity. Subsequently, whole-cell patch-clamp recordings revealed heterogeneous effects of RXFP3 activation in the IGL by the RXFP3 agonist, relaxin-3 B-chain/insulin-like peptide-5 A-chain (R3/I5). Identified, neuropeptide Y-positive IGL neurons, known to influence suprachiasmatic nucleus activity, were excited by R3/I5, whereas neurons of unidentified neurotransmitter content were either depolarized or displayed a decrease in action potential firing and/or membrane potential hyperpolarization. Our data identify a PAG to IGL relaxin-3/RXFP3 pathway that might convey stress-related information to key elements of the circadian system and influence behavioural state rhythmicity.
The physiological function of rhythmic firing in the neuronal networks of sensory systems has been linked with information coding. Also, neuronal oscillations in different frequency bands often change as a signature of brain state or sensory processing. Infra-slow oscillation (ISO) in the neuronal firing dependent on the retinal network has been described previously in the structures of the subcortical visual system. In the present study, we show for the first time that firing of ISO neurons in the lateral geniculate nucleus is also characterized by a harmonic discharge pattern (i.e. action potentials are separated by the intervals governed by fundamental frequency in the gamma range: ∼35 Hz). A similar phenomenon was recently described in the suprachiasmatic nuclei of the hypothalamus: the master biological clock. We found that both gamma and ISO rhythms were synchronized within and between ipsilateral nuclei of the subcortical visual system and were dependent on the retinal activity of the contralateral eye. These oscillatory patterns were differentially influenced by transient and prolonged light stimulation with respect to both frequency change direction and sustainability. The results of the present study show that the firing pattern of neurons in the subcortical visual system is shaped by oscillations from infra-slow and gamma frequency bands that are plausibly generated by the retinal network. Additionally, the results demonstrate that both rhythms are not a distinctive feature of image or non-image forming visual systems but, instead, they comprise two channels carrying distinctive properties of photic information.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.