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Interpeduncular nucleus

Hajime Shiotani, Muneaki Miyata, Kiyohito Mizutani, Shujie Wang, Akira Mizoguchi, Hideki Mochizuki, Kenji Mandai, Yoshimi Takai
The medial habenula (MHb) receives septal inputs and sends efferents to the interpeduncular nucleus and is implicated in stress, depression, memory, and nicotine withdrawal syndrome. We previously showed by immunofluorescence microscopy that the cell adhesion molecule nectin-2α is expressed in the cholinergic neurons in the developing and adult mouse MHbs and localized at the boundary between the adjacent somata of clustered cholinergic neurons where the voltage-gated A-type K+ channel Kv4.2 is localized. We further showed by immunoelectron microscopy that Kv4...
November 5, 2018: Molecular and Cellular Neurosciences
Chunpeng Xu, Yanfei Sun, Xuewei Cai, Tingting You, Hongzhe Zhao, Yang Li, Hua Zhao
The habenula is a nuclear complex composed of the lateral habenula (LHb) and medial habenula (MHb), two distinct structures. Much progress has been made to emphasize the role of the LHb in the pathogenesis of depression. In contrast, relatively less research has focused on the MHb. However, in recent years, the role of the MHb has begun to gain increasing attention. The MHb connects to the interpeduncular nucleus (IPN) both morphologically and functionally. The MHb-IPN pathway plays an important role in regulating higher brain functions, including cognition, reward, and decision making...
2018: Frontiers in Behavioral Neuroscience
Benoit Forget, Petra Scholze, Francina Langa, Carole Morel, Stephanie Pons, Sarah Mondoloni, Morgane Besson, Romain Durand-de Cuttoli, Audrey Hay, Ludovic Tricoire, Bertrand Lambolez, Alexandre Mourot, Philippe Faure, Uwe Maskos
Tobacco addiction is a chronic and relapsing disorder with an important genetic component that represents a major public health issue. Meta-analysis of large-scale human genome-wide association studies (GWASs) identified a frequent non-synonymous SNP in the gene coding for the α5 subunit of nicotinic acetylcholine receptors (α5SNP), which significantly increases the risk for tobacco dependence and delays smoking cessation. To dissect the neuronal mechanisms underlying the vulnerability to nicotine addiction in carriers of the α5SNP, we created rats expressing this polymorphism using zinc finger nuclease technology and evaluated their behavior under the intravenous nicotine-self-administration paradigm...
October 22, 2018: Current Biology: CB
Erica Seigneur, Jai S Polepalli, Thomas C Südhof
Cerebellins are important neurexin ligands that remain incompletely understood. Two critical questions in particular remain unanswered: do different cerebellins perform distinct functions, and do these functions act in the initial establishment of synapses or in rendering nascent synapses capable of normal synaptic transmission? Here we show that in mice, Cbln2 and Cbln4 are expressed in the medial habenula (MHb) nucleus in different types of neurons that project to distinct target neurons in the interpeduncular nucleus...
October 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
Torsten Weiss, René Bernard, Hans-Gert Bernstein, Rüdiger W Veh, Gregor Laube
The dorsal diencephalic conduction system connects limbic forebrain structures to monaminergic mesencephalic nuclei via a distinct relay station, the habenular complexes. Both habenular nuclei, the lateral as well as the medial nucleus, are considered to play a prominent role in mental disorders like major depression. Herein, we investigate the effect of the polyamine agmatine on the electrical activity of neurons within the medial habenula in rat. We present evidence that agmatine strongly decreases spontaneous action potential firing of medial habenular neurons by activating I1-type imidazoline receptors...
September 24, 2018: Translational Psychiatry
Shannon L Wolfman, Daniel F Gill, Fili Bogdanic, Katie Long, Ream Al-Hasani, Jordan G McCall, Michael R Bruchas, Daniel S McGehee
Nicotine use can lead to dependence through complex processes that are regulated by both its rewarding and aversive effects. Recent studies show that aversive nicotine doses activate excitatory inputs to the interpeduncular nucleus (IPN) from the medial habenula (MHb), but the downstream targets of the IPN that mediate aversion are unknown. Here we show that IPN projections to the laterodorsal tegmentum (LDTg) are GABAergic using optogenetics in tissue slices from mouse brain. Selective stimulation of these IPN axon terminals in LDTg in vivo elicits avoidance behavior, suggesting that these projections contribute to aversion...
July 13, 2018: Nature Communications
Jenni Kononoff, Marsida Kallupi, Adam Kimbrough, Dana Conlisk, Giordano de Guglielmo, Olivier George
GPR139 is an orphan G protein-coupled receptor (GPCR) that is expressed mainly in the brain, with the highest expression in the medial habenula. The modulation of GPR139 receptor function has been hypothesized to be beneficial in the treatment of some mental disorders, but behavioral studies have not yet provided causal evidence of the role of GPR139 in brain dysfunction. Because of the high expression of GPR139 in the habenula, a critical brain region in addiction, we hypothesized that GPR139 may play role in alcohol dependence...
May 2018: ENeuro
Glenn Morton, Nailyam Nasirova, Daniel W Sparks, Matt Brodsky, Sanghavy Sivakumaran, Evelyn K Lambe, Eric E Turner
Genetic studies have shown an association between smoking and variation at the CHRNA5/A3/B4 gene locus, encoding the α5, α3 and β4 nicotinic receptor subunits. The α5 receptor has been specifically implicated because smoking-associated haplotypes contain a coding variant in the CHRNA5 gene. The Chrna5/a3/b4 locus is conserved in rodents, and the restricted expression of these subunits suggests neural pathways through which the reinforcing and aversive properties of nicotine may be mediated. Here we show that in the interpeduncular nucleus (IP), the site of the highest Chrna5 mRNA expression in rodents, electrophysiological responses to nicotinic acetylcholine receptor stimulation are markedly reduced in α5 null mice...
June 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Katja Baur, Arian Hach, Rick E Bernardi, Rainer Spanagel, Hilmar Bading, C Peter Bengtson
Despite the reduced life expectancy and staggering financial burden of medical treatment associated with tobacco smoking, the molecular, cellular, and ensemble adaptations associated with chronic nicotine consumption remain poorly understood. Complex circuitry interconnecting dopaminergic and cholinergic regions of the midbrain and mesopontine tegmentum are critical for nicotine associated reward. Yet our knowledge of the nicotine activation of these regions is incomplete, in part due to their cell type diversity...
September 1, 2018: Journal of Comparative Neurology
Hajime Shiotani, Muneaki Miyata, Yu Itoh, Shujie Wang, Aika Kaito, Akira Mizoguchi, Miwako Yamasaki, Masahiko Watanabe, Kenji Mandai, Hideki Mochizuki, Yoshimi Takai
The medial habenula (MHb), implicated in stress, depression, memory, and nicotine withdrawal syndromes, receives septal inputs and sends efferents to the interpeduncular nucleus. We previously showed that the immunoglobulin-like cell adhesion molecules (CAMs) nectin-2α and nectin-2δ are expressed in astrocytes in the brain, but their expression in neurons remains unknown. We showed here by immunofluorescence microscopy that nectin-2α, but not nectin-2δ, was prominently expressed in the cholinergic neurons in the developing and adult MHbs and localized at the boundary between the adjacent somata of the clustered cholinergic neurons where the voltage-gated A-type K+ channel Kv4...
June 15, 2018: Journal of Comparative Neurology
Justin N Siemian, Shushan Jia, Jian-Feng Liu, Yanan Zhang, Jun-Xu Li
Chronic pain is a significant public health problem with a lack of safe and effective analgesics. The imidazoline I2 receptor (I2 R) is a promising analgesic target, but the neuroanatomical structures involved in mediating I2 R-associated behaviors are unknown. I2 Rs are enriched in the arcuate nucleus, dorsal raphe (DR), interpeduncular nucleus, lateral mammillary body, medial habenula, nucleus accumbens (NAc) and paraventricular nucleus; thus, this study investigated the antinociceptive and hypothermic effects of microinjections of the I2 R agonist 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI)...
May 2018: European Journal of Neuroscience
Marc Fakhoury
The tail of the ventral tegmental area (tVTA) is a recently identified structure that exerts a major inhibitory drive onto midbrain dopamine (DA) neurons. Also referred to as the rostromedial tegmental nucleus (RMTg), the tVTA is a cluster of gamma-aminobutyric acid (GABA)ergic neurons that starts within the posterior end of the VTA, where it is restricted dorsolateral to the caudal part of the interpeduncular nucleus, and extends into the pons. First identified in the rat, the tVTA has been described in many species, including mice and monkeys, as a region exhibiting similar anatomical and behavioral properties; it receives strong excitatory inputs from the lateral habenula (LHb), conveys negative reward-related information, and inhibits midbrain DA neuron activity...
June 8, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Leila Khatami, Fariba Khodagholi, Fereshteh Motamedi
The Interpedundular nucleus (IPN) is a small midbrain structure located deeply between the two cerebral peduncles. The strategic placement of this nucleus makes it a possible relay between structures involved in the modulation of hippocampal theta rhythm activity. In this study we aimed to investigate how reversible inactivation of IPN could affect the acquisition, consolidation and retrieval phases of memory in passive avoidance (PA) and Morris water maze (MWM) tasks. To support our data, molecular studies were performed in order to detect possible changes in the expression of proteins related to learning and memory in the hippocampus...
April 16, 2018: Behavioural Brain Research
Jasenka Zubcevic, Jacqueline Watkins, Pablo D Perez, Luis M Colon-Perez, Maureen T Long, Marcelo Febo, Linda Hayward
Individuals with anxiety/depression often have exaggerated cardiovascular responses to stressful stimuli and a comorbidity with hypertension. Alternatively, individuals with hypertension can be more anxious. In the present study cardiovascular changes were evaluated during behavioral testing of anxious behavior on the elevated plus maze (EPM) in the spontaneously hypertensive rat (SHR), a rodent model of neurogenic hypertension, and compared to the response of the more anxious, but normotensive, Wistar-Kyoto rat (WKY)...
November 27, 2017: Brain Imaging and Behavior
Jessica L Ables, Andreas Görlich, Beatriz Antolin-Fontes, Cuidong Wang, Sylvia M Lipford, Michael H Riad, Jing Ren, Fei Hu, Minmin Luo, Paul J Kenny, Nathaniel Heintz, Ines Ibañez-Tallon
Repeated exposure to drugs of abuse can produce adaptive changes that lead to the establishment of dependence. It has been shown that allelic variation in the α5 nicotinic acetylcholine receptor (nAChR) gene CHRNA5 is associated with higher risk of tobacco dependence. In the brain, α5-containing nAChRs are expressed at very high levels in the interpeduncular nucleus (IPN). Here we identified two nonoverlapping α5 + cell populations (α5- Amigo1 and α5- Epyc ) in mouse IPN that respond differentially to nicotine...
December 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
Frédéric Laberge, Allison Smith
The habenular complex and its associated axonal pathways are often thought of as phylogenetically conserved features of the brain among vertebrates despite the fact that detailed studies of this brain region are limited to a few species. Here, the gross morphology and axonal projection pattern of the habenular complex of an anuran amphibian, the fire-bellied toad Bombina orientalis, was studied to allow comparison with the situation in other vertebrates. Axonal pathways were traced using biocytin applications in dissected brain preparations...
2017: Brain, Behavior and Evolution
Sara Roberson, Marnie E Halpern
Accumulating evidence has reinforced that the habenular region of the vertebrate dorsal forebrain is an essential integrating center, and a region strongly implicated in neurological disorders and addiction. Despite the important and diverse neuromodulatory roles the habenular nuclei play, their development has been understudied. The emphasis of this review is on the dorsal habenular nuclei of zebrafish, homologous to the medial nuclei of mammals, as recent work has revealed new information about the signaling pathways that regulate their formation...
June 2018: Seminars in Cell & Developmental Biology
Ian McLaughlin, John A Dani, Mariella De Biasi
Abstinence from chronic use of addictive drugs triggers an aversive withdrawal syndrome that compels relapse and deters abstinence. Many features of this syndrome are common across multiple drugs, involving both affective and physical symptoms. Some of the network signaling underlying withdrawal symptoms overlaps with activity that is associated with aversive mood states, including anxiety and depression. Given these shared features, it is not surprising that a particular circuit, the dorsal diencephalic conduction system, and the medial habenula (MHb) and interpeduncular nucleus (IPN), in particular, have been identified as critical to the emergence of aversive states that arise both as a result and, independently, of drug addiction...
August 2017: Journal of Neurochemistry
Peter Koppensteiner, Riccardo Melani, Ipe Ninan
The medial habenula-interpeduncular nucleus (MHb-IPN) pathway, which connects the limbic forebrain to the midbrain, has recently been implicated in aversive behaviors. The MHb-IPN circuit is characterized by a unique topographical organization, an excitatory role of GABA, and a prominent co-release of neurotransmitters and neuropeptides. However, little is known about synaptic plasticity in this pathway. An application of a high-frequency stimulation resulted in a long-lasting potentiation of glutamate release in IPN neurons...
August 1, 2017: Cell Reports
Susanna Molas, Rubing Zhao-Shea, Liwang Liu, Steven R DeGroot, Paul D Gardner, Andrew R Tapper
Novelty preference (NP) is an evolutionarily conserved, essential survival mechanism often dysregulated in neuropsychiatric disorders. NP is mediated by a motivational dopamine signal that increases in response to novel stimuli, thereby driving exploration. However, the mechanism by which once-novel stimuli transition to familiar stimuli is unknown. Here we describe a neuroanatomical substrate for familiarity signaling, the interpeduncular nucleus (IPN) of the midbrain, which is activated as novel stimuli become familiar with multiple exposures...
September 2017: Nature Neuroscience
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