| The nucleus incertus (NI) is a distinct area within the brainstem near the posterior part of the tegmentum. This part of the brain consists of some heterogeneous neurons that play roles in different functions, including response to stress, arousal, learning, and modulating hippocampal theta rhythm. Orexin neuropeptides also have widespread distributions and overlapping actions within the NI. However, the actions of the orexin receptors in the NI are not well characterized. In the present study, the effect of post-training and pre-probe of trial intra-NI administration of SB-33486-A (OX1R antagonist) (12 μg/0.5μl) and TCS-OX2-29 (OX2R antagonist) (10 μg/0.5 μl) on consolidation and retrieval in Morris Water Maze (MWM) task was examined. In the experiment 1, rats were trained in MWM and immediately after every training received injections of Dimethyl sulfoxide (DMSO) (control group), SB-334867-A, and TCS-OX2-29 into NI. Experiment 2 was similar to experiment 1 except rats received DMSO, SB-33486-A, and TCS-OX2-29, 15 minutes before the probe test. In subsequent experiments, probe and visible tests were performed after the last training and distance moved, escape latency, and velocity were recorded. In experiment 3, rats trained in experiments 1 and 2 immediately after the probe test were given trials for visuomotor coordination assessment on the visible platform. The results showed that the spatial reference memory consolidation phase was significantly impaired by SB-334867-A or TCS-OX2-29 (P < 0.05), while the retrieval phase was not affected (P > 0.05). Therefore, it can be concluded that the orexinergic system in the NI has a key role in consolidation in rats through both OX1 and OX2 receptors. |
- Olucha‐Bordonau FE, Teruel V, Barcia‐González J, Ruiz‐Torner A, Valverde‐Navarro AA, Martínez‐Soriano F. Cytoarchitecture and efferent projections of the nucleus incertus of the rat. Journal of Comparative Neurology. 2003;464(1):62-97.
- Ma S, Bonaventure P, Ferraro T, Shen P-J, Burazin TC, Bathgate RA, et al. Relaxin-3 in GABA projection neurons of nucleus incertus suggests widespread influence on forebrain circuits via G-protein-coupled receptor-135 in the rat. Neuroscience. 2007;144(1):165-90.
- Cervera-Ferri A, Rahmani Y, Martínez-Bellver S, Teruel-Martí V, Martínez-Ricós J. Glutamatergic projection from the nucleus incertus to the septohippocampal system. Neuroscience letters. 2012;517(2):71-6.
- Bittencourt JC, Sawchenko PE. Do centrally administered neuropeptides access cognate receptors?: an analysis in the central corticotropin-releasing factor system. Journal of Neuroscience. 2000;20(3):1142-56.
- Potter E, Sutton S, Donaldson C, Chen R, Perrin M, Lewis K, et al. Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary. Proceedings of the National Academy of Sciences. 1994;91(19):8777-81.
- Goto M, Swanson LW, Canteras NS. Connections of the nucleus incertus. Journal of Comparative Neurology. 2001;438(1):86-122.
- Banerjee A, Ma S, Ortinau S, Smith CM, Layfield S, Burazin TC, et al., editors. Relaxin-3 neurons in the nucleus incertus–projection patterns, response to swim stress and relaxin-3 neuronal signalling. Soc Neurosci Abstr; 2005.
- Callander GE, Ma S, Ganella DE, Wimmer VC, Gundlach AL, Thomas WG, et al. Silencing relaxin-3 in nucleus incertus of adult rodents: a viral vector-based approach to investigate neuropeptide function. PloS one. 2012;7(8):e42300.
- Smith CM, Ryan PJ, Hosken IT, Ma S, Gundlach AL. Relaxin-3 systems in the brain—the first 10 years. Journal of Chemical Neuroanatomy. 2011;42(4):262-75.
- Swanson LW. Cerebral hemisphere regulation of motivated behavior. Brain Research. 2000;886(1-2):113-64.
- Tanaka M. Relaxin‐3/insulin‐like peptide 7, a neuropeptide involved in the stress response and food intake. The FEBS Journal. 2010;277(24):4990-7.
- Blasiak A, Siwiec M, Grabowiecka A, Blasiak T, Czerw A, Blasiak E, et al. Excitatory orexinergic innervation of rat nucleus incertus–Implications for ascending arousal, motivation and feeding control. Neuropharmacology. 2015;99:432-47.
- De Lecea L, Kilduff T, Peyron C, Gao X-B, Foye P, Danielson P, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proceedings of the National Academy of Sciences. 1998;95(1):322-7.
- Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92(4):573-85.
- Akbari E, Motamedi F, Naghdi N, Noorbakhshnia M. The effect of antagonization of orexin 1 receptors in CA1 and dentate gyrus regions on memory processing in passive avoidance task. Behavioural brain research. 2008;187(1):172-7.
- Mahler SV, Moorman DE, Smith RJ, James MH, Aston-Jones G. Motivational activation: a unifying hypothesis of orexin/hypocretin function. Nature neuroscience. 2014;17(10):1298-303.
- Rahmani B, Ghashghayi E, Zendehdel M, Khodadadi M, Hamidi B. The crosstalk between brain mediators regulating food intake behavior in birds: a review. International Journal of Peptide Research and Therapeutics. 2021;27(4):2349-70.
- Dang R, Chen Q, Song J, He C, Zhang J, Xia J, et al. Orexin knockout mice exhibit impaired spatial working memory. Neuroscience letters. 2018;668:92-7.
- Paxinos G, Watson C. The rat brain in stereotaxic coordinates: hard cover edition: Elsevier; 2006.
- Ardeshiri MR, Hosseinmardi N, Akbari E. The effect of orexin 1 and orexin 2 receptors antagonisms in the basolateral amygdala on memory processing in a passive avoidance task. Physiology & Behavior. 2017;174:42-8.
- Nategh M, Nikseresht S, Khodagholi F, Motamedi F. Inactivation of nucleus incertus impairs passive avoidance learning and long term potentiation of the population spike in the perforant path-dentate gyrus evoked field potentials in rats. Neurobiology of Learning and Memory. 2016;130:185-93.
- Ma S, Blasiak A, Olucha‐Bordonau FE, Verberne AJ, Gundlach AL. Heterogeneous responses of nucleus incertus neurons to corticotrophin‐releasing factor and coherent activity with hippocampal theta rhythm in the rat. The Journal of Physiology. 2013;591(16):3981-4001.
- Nategh M, Nikseresht S, Khodagholi F, Motamedi F. Nucleus incertus inactivation impairs spatial learning and memory in rats. Physiology & Behavior. 2015;139:112-20.
- Resae A, Yousefi M, Naeimi S, Mahdavi A. Effects of Occupational Formaldehyde Exposure on Passive Avoidance Conditioning and Anxiety Levels in Wistar rats. Iranian Journal of Veterinary Medicine. 2022. In press. doi: 10.22059/ijvm.2022.338561.1005241
- Ma S, Smith CM, Blasiak A, Gundlach AL. Distribution, physiology and pharmacology of relaxin‐3/RXFP3 systems in brain. British Journal of Pharmacology. 2017;174(10):1034-48.
- Ardeshiri MR, Hosseinmardi N, Akbari E. The basolateral amygdala orexin 1 and 2 receptors' involvement in modulating spatial reference memory. Brain Research. 2019;1704:16-25.
|
