Topic: relaxin-3

The retrosplenial cortex (RSC) is known for its pivotal role in contextual fear conditioning, receiving inputs from both corticocortical and subcortical pathways, including the nucleus incertus in the pontine tegmentum. This region contains a GABAergic projection rich in relaxin-3 (RLN3), which acts via its Gi/o-protein-coupled receptor, RXFP3. To investigate the involvement of this peptidergic system in contextual fear conditioning, we bilaterally injected adult rat RSC with an adeno-associated virus (AAV) expressing the chimeric RXFP3 agonist R3/I5 or a control AAV and subjected them to cont

The hypothalamic, peptide hormone, oxytocin (OXT), is a powerful modulator of social-, stress- and anxiety-related behaviors, as is the brainstem, neuropeptide relaxin-3 (RLN3). Recent studies indicate the involvement of KCNQ potassium channels in neuronal OXT and RLN3 signaling, with these neuropeptides displaying opposing excitatory and inhibitory actions, respectively. OXT receptors (OXTR) and RLN3 receptors (RXFP3) are expressed by neurons in the rat ventral hippocampal CA3 area (vCA3), which is involved in social behavior and anxiety control; but the possible interaction between OXT and R

Early-life stress (ELS) disrupts brain development and predisposes sufferers to stress-related disorders and compulsive behaviour in adulthood. Accumulating evidence connects these disorders with neurons within the stress-sensitive, brainstem nucleus incertus (NI), which synthesize the neuropeptides, relaxin-3 (RLN3) and cholecystokinin (CCK). Although NI RLN3 neurons are implicated in stress responses, arousal and drug-seeking behaviour, their vulnerability to stress during development has not been explored, and little is known about NI CCK neurons. Therefore, this study investigated the infl

The ventral hippocampus (vHPC) is a brain locus centrally involved in the control of stress and anxiety, with dysfunction of its interneuron network strongly implicated in clinical anxiety-related disorders. The vHPC is heavily innervated by neurons in the pontine tegmental, nucleus incertus (NI) – the primary source of the neuropeptide, relaxin-3 (RLN3), in the rat brain. Intriguingly, sustained activation of the RLN3 receptor, RXFP3, in the vHPC of rats increased anxiety and social avoidance [1], yet the precise underlying neuronal mechanisms remain unknown. Therefore, this study investigate

The dentate gyrus of the ventral hippocampus (vDG) is strongly implicated in the pathophysiology of anxiety disorders. vDG is heavily innervated by the nucleus incertus (NI), a dorsal pontine locus highly sensitive to neurogenic stress and the main source of the neuropeptide, relaxin-3 (RLN3) in the rat brain. RLN3 receptor (RXFP3) activation has been shown to modulate behaviours, including stress-related anxiety. However, the effect of RLN3/RXFP3 signaling on vDG neuronal activity has not been examined. Therefore, this study investigated the influence of RLN3 on rat vDG neuronal activity ex v

The interpeduncular nucleus (IPN) is a highly complex and evolutionarily conserved midbrain locus involved in social novelty preference and anxiety control. The IPN is characterised by a high density of the nerve-growth factor (NGF) receptor, TrkA; and notably, social stress strongly promotes brain NGF synthesis. The IPN is densely innervated by the nucleus incertus (NI), a stress-sensitive region that is the primary source of the neuropeptide, relaxin-3 (RLN3). In turn, IPN innervates the ventral hippocampus (vHPC), another key locus for social behaviour and anxiety control. However, the natu

Accurate discrimination between new and familiar stimuli is essential for adaptive responses to an ever-changing environment, and disruptions in this process are strongly related to various neuropsychiatric disorders. Stress is a primary mediator of the development of novelty response-related deficiencies; therefore, we investigated the neuronal mechanisms underlying the possible control of the interpeduncular nucleus (IPN), implicated in signaling novelty preference, by the highly stress-sensitive, brainstem nucleus incertus (NI), the primary central source of the neuropeptide, relaxin-3 (RLN

This study aimed to delve into the role of the brainstem nucleus incertus (NI) as a structure involved in stress-response generation and its interactions with the ventral tegmental area (VTA), a key component of the brain's reward system. By tracing neural pathways using a retrograde viral vector, the NI-originating innervation of the VTA was confirmed within the midbrain of Sprague-Dawley rats. Immunohistochemical staining revealed that only a small percentage of NI neurons containing the relaxin-3 neuropeptide also project to the VTA, suggesting specialization of the connectivity between the

The brainstem nucleus incertus (NI) plays an important role in processing aversive stimuli and modulating stress response. In the midbrain, apart from the ventral tegmental area (VTA), the NI also innervates the rostromedial tegmental nucleus (RMTg) – the main inhibitory input to the dopaminergic (DA) system in mammals. In order to better understand the circuit’s anatomy, retrogradely transported viral vectors, carrying genes for fluorescent proteins, were unilaterally injected into the RMTg of Sprague-Dawley rats. The results show that the RMTg, unlike the VTA, receives bilateral innervation

The oxytocin (OXT) and relaxin-3 (RLN3) signalling systems are involved in shaping social and stress-related behaviours, but the interplay of these neural networks in relevant brain regions including the ventral hippocampus dentate gyrus (vDG), is under explored. The rat vDG is strongly innervated by OXT and RLN3-containing nerve fibres, but possible interactions of these neuropeptide systems in vDG are unknown. Therefore, we investigated the influence of OXT and RLN3 signalling, separately and in combination, on rat and human vDG neurons. Multiplex in situ hybridization (ISH) identified a mod