title: Relaxin-3 innervation of the intergeniculate leaflet of the rat thalamus - neuronal tract-tracing and in vitro electrophysiological studies.
abstract: 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.
authors: Department of Neurophysiology and Chronobiology, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland. anna.blasiak@uj.edu.pl
authors: Anna
authors: A
authors: Blasiak
authors: Tomasz
authors: T
authors: Blasiak
authors: Marian H
authors: MH
authors: Lewandowski
authors: Mohammed Akhter
authors: MA
authors: Hossain
authors: John D
authors: JD
authors: Wade
authors: Andrew L
authors: AL
authors: Gundlach
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012065:Relaxin / Q000378:metabolism*; D013312:Stress, Physiological; D013788:Thalamus / Q000166:cytology* / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C466742:RLN3 protein, rat; D012065:Relaxin