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Article ; Online: Understanding the habenula: A major node in circuits regulating emotion and motivation.

Ables, Jessica L / Park, Kwanghoon / Ibañez-Tallon, Inés

2023 Volume 190, Page(s) 106734

Abstract: Over the last decade, the understanding of the habenula has rapidly advanced from being an understudied brain area with the Latin name 'habena" meaning "little rein", to being considered a "major rein" in the control of key monoaminergic brain centers. ... ...

Abstract	Over the last decade, the understanding of the habenula has rapidly advanced from being an understudied brain area with the Latin name 'habena" meaning "little rein", to being considered a "major rein" in the control of key monoaminergic brain centers. This ancient brain structure is a strategic node in the information flow from fronto-limbic brain areas to brainstem nuclei. As such, it plays a crucial role in regulating emotional, motivational, and cognitive behaviors and has been implicated in several neuropsychiatric disorders, including depression and addiction. This review will summarize recent findings on the medial (MHb) and lateral (LHb) habenula, their topographical projections, cell types, and functions. Additionally, we will discuss contemporary efforts that have uncovered novel molecular pathways and synaptic mechanisms with a focus on MHb-Interpeduncular nucleus (IPN) synapses. Finally, we will explore the potential interplay between the habenula's cholinergic and non-cholinergic components in coordinating related emotional and motivational behaviors, raising the possibility that these two pathways work together to provide balanced roles in reward prediction and aversion, rather than functioning independently.
MeSH term(s)	Motivation ; Habenula/metabolism ; Interpeduncular Nucleus/metabolism ; Emotions
Language	English
Publishing date	2023-03-16
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2023.106734
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Article: Precise 3D Localization of Intracerebral Implants with a simple Brain Clearing Method.

Catanese, Julien / Murakami, Tatsuya / Kenny, Paul J / Ibanez-Tallon, Ines

bioRxiv : the preprint server for biology

2024

Abstract: Determining the localization of intracerebral implants in rodent brain stands as a critical final step in most physiological and behaviroral studies, especially when targeting deep brain nuclei. Conventional histological approaches, reliant on manual ... ...

Abstract	Determining the localization of intracerebral implants in rodent brain stands as a critical final step in most physiological and behaviroral studies, especially when targeting deep brain nuclei. Conventional histological approaches, reliant on manual estimation through sectioning and slice examination, are error-prone, potentially complicating data interpretation. Leveraging recent advances in tissue-clearing techniques and light-sheet fluorescence microscopy, we introduce a method enabling virtual brain slicing in any orientation, offering precise implant localization without the limitations of traditional tissue sectioning. To illustrate the method's utility, we present findings from the implantation of linear silicon probes into the midbrain interpeduncular nucleus (IPN) of anesthetized transgenic mice expressing chanelrhodopsin-2 and enhanced yellow fluorescent protein under the choline acetyltransferase (ChAT) promoter/enhancer regions (ChAT-Chr2-EYFP mice). Utilizing a fluorescent dye applied to the electrode surface, we visualized both the targeted area and the precise localization, enabling enhanced inter-subject comparisons. Three dimensional (3D) brain renderings, presented effortlessly in video format across various orientations, showcase the versatility of this approach.
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.22.573088
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Article ; Online: Local production of corticotropin-releasing hormone in prefrontal cortex modulates male-specific novelty exploration.

Riad, Michael H / Park, Kwanghoon / Ibañez-Tallon, Ines / Heintz, Nathaniel

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 49, Page(s) e2211454119

Abstract: Neuromodulatory substances can be released from distal afferents for communication between brain structures or produced locally to modulate neighboring circuit elements. Corticotropin-releasing hormone (CRH) from long-range neurons in the hypothalamus ... ...

Abstract	Neuromodulatory substances can be released from distal afferents for communication between brain structures or produced locally to modulate neighboring circuit elements. Corticotropin-releasing hormone (CRH) from long-range neurons in the hypothalamus projecting to the medial prefrontal cortex (mPFC) has been shown to induce anxiety-like behaviors. However, the role of CRH produced in the mPFC has not been investigated. Here we demonstrate that a specific class of mPFC interneurons that express CRH (CrhINs) releases CRH upon high-frequency stimulation to enhance excitability of layer 2/3 pyramidal cells (L2/3 PCs) expressing the CRH receptors. When stimulated at low frequency, CrhINs release GABA resulting in the inhibition of oxytocin receptor-expressing interneurons (OxtrINs) and L2/3 PCs. Conditional deletion of CRH in mPFC CrhINs and chemogenetic activation of CrhINs have opposite effects on novelty exploration in male but not in female mice, and do not affect anxiety-related behaviors in either males or females. Our data reveal that CRH produced by local interneurons in the mPFC is required for sex-specific novelty exploration and suggest that our understanding of complex behaviors may require knowledge of local and remote neuromodulatory action.
MeSH term(s)	Female ; Male ; Animals ; Mice ; Corticotropin-Releasing Hormone/genetics ; Prefrontal Cortex ; Receptors, Corticotropin-Releasing Hormone ; Pyramidal Cells ; Interneurons
Chemical Substances	Corticotropin-Releasing Hormone (9015-71-8) ; Receptors, Corticotropin-Releasing Hormone
Language	English
Publishing date	2022-11-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2211454119
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Article ; Online: Cell-Type-Specific Contributions of Medial Prefrontal Neurons to Flexible Behaviors.

Nakayama, Hirofumi / Ibañez-Tallon, Ines / Heintz, Nathaniel

The Journal of neuroscience : the official journal of the Society for Neuroscience

2018 Volume 38, Issue 19, Page(s) 4490–4504

Abstract: Behavioral flexibility and impulse control are necessary for successful execution of adaptive behavior. They are impaired in patients with damage to the prefrontal cortex (PFC) and in some clinically important conditions, such as obsessive-compulsive ... ...

Abstract	Behavioral flexibility and impulse control are necessary for successful execution of adaptive behavior. They are impaired in patients with damage to the prefrontal cortex (PFC) and in some clinically important conditions, such as obsessive-compulsive disorder. Although the medial prefrontal cortex (mPFC) has been investigated as a critical structure for behavioral flexibility and impulse control, the contribution of the underlying pyramidal neuron cell types in the mPFC remained to be understood. Here we show that interneuron-mediated local inactivation of pyramidal neurons in the mPFC of male and female mice induces both premature responses and choice bias, and establish that these impulsive and compulsive responses are modulated independently. Cell-type-specific photoinhibition of pyramidal deep layer corticostriatal or corticothalamic neurons reduces behavioral flexibility without inducing premature responses. Together, our data confirm the role of corticostriatal neurons in behavioral flexibility and demonstrate that flexible behaviors are also modulated by direct projections from deep layer corticothalamic neurons in the mPFC to midline thalamic nuclei.
MeSH term(s)	Algorithms ; Animals ; Behavior, Animal/physiology ; Choice Behavior ; Compulsive Behavior/psychology ; Corpus Striatum/cytology ; Corpus Striatum/physiology ; Female ; Impulsive Behavior ; Male ; Mice ; Mice, Inbred C57BL ; Neural Pathways/cytology ; Neural Pathways/physiology ; Neurons/physiology ; Optogenetics ; Prefrontal Cortex/physiology ; Pyramidal Cells/physiology ; Reaction Time ; Thalamus/cytology ; Thalamus/physiology
Language	English
Publishing date	2018-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.3537-17.2018
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Zs.A 1668: Show issues

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Article ; Online: β4-Nicotinic Receptors Are Critically Involved in Reward-Related Behaviors and Self-Regulation of Nicotine Reinforcement.

Husson, Marianne / Harrington, Lauriane / Tochon, Léa / Cho, Yoon / Ibañez-Tallon, Inés / Maskos, Uwe / David, Vincent

The Journal of neuroscience : the official journal of the Society for Neuroscience

2020 Volume 40, Issue 17, Page(s) 3465–3477

Abstract: Nicotine addiction, through smoking, is the principal cause of preventable mortality worldwide. Human genome-wide association studies have linked polymorphisms in ... ...

Abstract	Nicotine addiction, through smoking, is the principal cause of preventable mortality worldwide. Human genome-wide association studies have linked polymorphisms in the
MeSH term(s)	Animals ; Behavior, Animal/drug effects ; Conditioning, Operant/drug effects ; Discrimination Learning/drug effects ; Male ; Mice ; Mice, Knockout ; Motivation/drug effects ; Motor Activity/drug effects ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Nicotine/administration & dosage ; Nicotinic Agonists/administration & dosage ; Receptors, Nicotinic/genetics ; Receptors, Nicotinic/metabolism ; Reward ; Self Administration ; Self-Control ; Ventral Tegmental Area/drug effects
Chemical Substances	Chrnb4 protein, mouse ; Nerve Tissue Proteins ; Nicotinic Agonists ; Receptors, Nicotinic ; Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2020-03-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.0356-19.2020
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Article ; Online: "The King is dead": Checkmating ion channels with tethered toxins.

Auer, Sebastian / Ibañez-Tallon, Inés

Toxicon : official journal of the International Society on Toxinology

2010 Volume 56, Issue 8, Page(s) 1293–1298

Abstract: The quickest possible checkmate in the game of chess requires two moves using a pawn and the queen. Metaphorically speaking, the pawn (a membrane tether) and the queen (a toxin) work together to checkmate an ion channel within a neuronal circuit. This ... ...

Abstract	The quickest possible checkmate in the game of chess requires two moves using a pawn and the queen. Metaphorically speaking, the pawn (a membrane tether) and the queen (a toxin) work together to checkmate an ion channel within a neuronal circuit. This strategy termed "tethered toxin" (t-toxin) is based on the use of genetically encoded peptide toxins that are anchored to the cell-membrane via a glycolipid or transmembrane tether. Because of their mode of action at the cell surface, t-toxins act only on ion channels and receptors of the cell that is expressing the t-toxin, and not on identical receptors present in neighboring cells that do not express the t-toxin. In this mini-review we discuss the design of these genetic tools and their application for cell-specific and temporal manipulation of ion channel-mediated activities in vivo.
MeSH term(s)	Animals ; Cell Membrane/metabolism ; Humans ; Ion Channel Gating/genetics ; Ion Channel Gating/physiology ; Ion Channels/antagonists & inhibitors ; Ion Transport/genetics ; Ion Transport/physiology ; Membrane Transport Modulators/chemistry ; Membrane Transport Modulators/metabolism ; Mice ; Models, Biological ; Models, Molecular ; Neurotransmitter Agents/metabolism ; Organisms, Genetically Modified/metabolism ; Rats ; Substrate Specificity ; Toxins, Biological/chemistry ; Toxins, Biological/genetics ; Toxins, Biological/physiology ; Venoms/chemistry ; Venoms/genetics ; Zebrafish/metabolism
Chemical Substances	Ion Channels ; Membrane Transport Modulators ; Neurotransmitter Agents ; Toxins, Biological ; Venoms
Language	English
Publishing date	2010-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	204479-1
ISSN	1879-3150 ; 0041-0101
ISSN (online)	1879-3150
ISSN	0041-0101
DOI	10.1016/j.toxicon.2010.09.016
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Zs.A 501: Show issues

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Article ; Online: A Cortical Circuit for Sexually Dimorphic Oxytocin-Dependent Anxiety Behaviors.

Li, Kun / Nakajima, Miho / Ibañez-Tallon, Ines / Heintz, Nathaniel

Cell

2016 Volume 167, Issue 1, Page(s) 60–72.e11

Abstract: The frequency of human social and emotional disorders varies significantly between males and females. We have recently reported that oxytocin receptor interneurons (OxtrINs) modulate female sociosexual behavior. Here, we show that, in male mice, OxtrINs ... ...

Abstract	The frequency of human social and emotional disorders varies significantly between males and females. We have recently reported that oxytocin receptor interneurons (OxtrINs) modulate female sociosexual behavior. Here, we show that, in male mice, OxtrINs regulate anxiety-related behaviors. We demonstrate that corticotropin-releasing-hormone-binding protein (CRHBP), an antagonist of the stress hormone CRH, is specifically expressed in OxtrINs. Production of CRHBP blocks the CRH-induced potentiation of postsynaptic layer 2/3 pyramidal cell activity of male, but not female, mice, thus producing an anxiolytic effect. Our data identify OxtrINs as critical for modulation of social and emotional behaviors in both females and males and reveal a molecular mechanism that acts on local medial prefrontal cortex (mPFC) circuits to coordinate responses to OXT and CRH. They suggest that additional studies of the impact of the OXT/OXTR and CRHBP/CRH pathways in males and females will be important in development of gender-specific therapies.
MeSH term(s)	Animals ; Anxiety/metabolism ; Anxiety/psychology ; Behavior, Animal ; Carrier Proteins/metabolism ; Corticotropin-Releasing Hormone/metabolism ; Female ; Interneurons/metabolism ; Long-Term Potentiation ; Male ; Metabolic Networks and Pathways ; Mice ; Oxytocin/metabolism ; Prefrontal Cortex/metabolism ; Receptors, Oxytocin/metabolism ; Sex Characteristics ; Sex Factors
Chemical Substances	Carrier Proteins ; Receptors, Oxytocin ; corticotropin releasing factor-binding protein (134773-81-2) ; Oxytocin (50-56-6) ; Corticotropin-Releasing Hormone (9015-71-8)
Language	English
Publishing date	2016-09-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2016.08.067
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 58: Show issues

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Article ; Online: Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates.

Broms, Jonas / Antolin-Fontes, Beatriz / Tingström, Anders / Ibañez-Tallon, Ines

The Journal of comparative neurology

2014 Volume 523, Issue 3, Page(s) 359–380

Abstract: The habenula is a phylogenetically conserved brain structure in the epithalamus. It is a major node in the information flow between fronto-limbic brain regions and monoaminergic brainstem nuclei, and is thus anatomically and functionally ideally ... ...

Abstract	The habenula is a phylogenetically conserved brain structure in the epithalamus. It is a major node in the information flow between fronto-limbic brain regions and monoaminergic brainstem nuclei, and is thus anatomically and functionally ideally positioned to regulate emotional, motivational, and cognitive behaviors. Consequently, the habenula may be critically important in the pathophysiology of psychiatric disorders such as addiction and depression. Here we investigated the expression pattern of GPR151, a G protein-coupled receptor (GPCR), whose mRNA has been identified as highly and specifically enriched in habenular neurons by in situ hybridization and translating ribosome affinity purification (TRAP). In the present immunohistochemical study we demonstrate a pronounced and highly specific expression of the GPR151 protein in the medial and lateral habenula of rodent brain. Specific expression was also seen in efferent habenular fibers projecting to the interpeduncular nucleus, the rostromedial tegmental area, the rhabdoid nucleus, the mesencephalic raphe nuclei, and the dorsal tegmental nucleus. Using confocal microscopy and quantitative colocalization analysis, we found that GPR151-expressing axons and terminals overlap with cholinergic, substance P-ergic, and glutamatergic markers. Virtually identical expression patterns were observed in rat, mouse, and zebrafish brains. Our data demonstrate that GPR151 is highly conserved, specific for a subdivision of the habenular neurocircuitry, and constitutes a promising novel target for psychiatric drug development.
MeSH term(s)	Animals ; Axons/physiology ; Choline O-Acetyltransferase/metabolism ; Habenula/cytology ; Humans ; Interpeduncular Nucleus/physiology ; Mesencephalon/anatomy & histology ; Mesencephalon/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Net/metabolism ; Neurofilament Proteins/metabolism ; Neurons/metabolism ; Rats ; Rats, Wistar ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Neuropeptide/genetics ; Receptors, Neuropeptide/metabolism ; Species Specificity ; Substance P/metabolism ; Tryptophan Hydroxylase/metabolism ; Tyrosine 3-Monooxygenase/metabolism ; Vertebrates/anatomy & histology ; Vertebrates/metabolism ; Vesicular Glutamate Transport Proteins/metabolism ; Zebrafish ; beta-Galactosidase/genetics ; beta-Galactosidase/metabolism
Chemical Substances	Neurofilament Proteins ; Npbwr1 protein, mouse ; Receptors, G-Protein-Coupled ; Receptors, Neuropeptide ; Vesicular Glutamate Transport Proteins ; neurofilament protein H (108688-71-7) ; Substance P (33507-63-0) ; Tyrosine 3-Monooxygenase (EC 1.14.16.2) ; Tryptophan Hydroxylase (EC 1.14.16.4) ; Choline O-Acetyltransferase (EC 2.3.1.6) ; beta-Galactosidase (EC 3.2.1.23)
Language	English
Publishing date	2014-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3086-7
ISSN	1096-9861 ; 0021-9967 ; 0092-7317
ISSN (online)	1096-9861
ISSN	0021-9967 ; 0092-7317
DOI	10.1002/cne.23664
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Article ; Online: Tethering toxins and peptide ligands for modulation of neuronal function.

Ibañez-Tallon, Inés / Nitabach, Michael N

Current opinion in neurobiology

2011 Volume 22, Issue 1, Page(s) 72–78

Abstract: Tethering genetically encoded peptide toxins or ligands close to their point of activity at the cell plasma membrane provides a new approach to the study of cell networks and neuronal circuits, as it allows selective targeting of specific cell ... ...

Abstract	Tethering genetically encoded peptide toxins or ligands close to their point of activity at the cell plasma membrane provides a new approach to the study of cell networks and neuronal circuits, as it allows selective targeting of specific cell populations, enhances the working concentration of the ligand or blocker peptide, and permits the engineering of a large variety of t-peptides (e.g., including use of fluorescent markers, viral vectors and point mutation variants). This review describes the development of tethered toxins (t-toxins) and peptides derived from the identification of the cell surface nicotinic acetylcholine receptor (nAChR) modulator lynx1, the existence of related endogenous cell surface modulators of nAChR and AMPA receptors, and the application of the t-toxin and t-neuropeptide technology to the dissection of neuronal circuits in metazoans.
MeSH term(s)	Animals ; Ligands ; Neuropeptides ; Neurosciences/methods ; Neurotoxins/genetics ; Neurotoxins/metabolism ; Protein Engineering/methods ; Receptors, Nicotinic/genetics ; Receptors, Nicotinic/metabolism
Chemical Substances	Ligands ; Neuropeptides ; Neurotoxins ; Receptors, Nicotinic
Language	English
Publishing date	2011-11-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1078046-4
ISSN	1873-6882 ; 0959-4388
ISSN (online)	1873-6882
ISSN	0959-4388
DOI	10.1016/j.conb.2011.11.003
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Article ; Online: The habenular G-protein-coupled receptor 151 regulates synaptic plasticity and nicotine intake.

Antolin-Fontes, Beatriz / Li, Kun / Ables, Jessica L / Riad, Michael H / Görlich, Andreas / Williams, Maya / Wang, Cuidong / Lipford, Sylvia M / Dao, Maria / Liu, Jianxi / Molina, Henrik / Heintz, Nathaniel / Kenny, Paul J / Ibañez-Tallon, Ines

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 10, Page(s) 5502–5509

Abstract: The habenula, an ancient small brain area in the epithalamus, densely expresses nicotinic acetylcholine receptors and is critical for nicotine intake and aversion. As such, identification of strategies to manipulate habenular activity may yield ... ...

Abstract	The habenula, an ancient small brain area in the epithalamus, densely expresses nicotinic acetylcholine receptors and is critical for nicotine intake and aversion. As such, identification of strategies to manipulate habenular activity may yield approaches to treat nicotine addiction. Here we show that GPR151, an orphan G-protein-coupled receptor (GPCR) highly enriched in the habenula of humans and rodents, is expressed at presynaptic membranes and synaptic vesicles and associates with synaptic components controlling vesicle release and ion transport. Deletion of
MeSH term(s)	Animals ; CHO Cells ; Cricetulus ; GTP-Binding Protein alpha Subunits, Gi-Go/metabolism ; Habenula/metabolism ; Habenula/physiology ; Humans ; Mice, Knockout ; Neuronal Plasticity/drug effects ; Neuronal Plasticity/genetics ; Neuronal Plasticity/physiology ; Nicotine/administration & dosage ; Nicotine/metabolism ; Nicotinic Agonists/administration & dosage ; Nicotinic Agonists/metabolism ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/physiology ; Substance-Related Disorders/metabolism ; Synaptic Transmission/genetics ; Synaptic Transmission/physiology
Chemical Substances	GPR151 protein, human ; Gpr151 protein, mouse ; Nicotinic Agonists ; Receptors, G-Protein-Coupled ; Nicotine (6M3C89ZY6R) ; GTP-Binding Protein alpha Subunits, Gi-Go (EC 3.6.5.1)
Language	English
Publishing date	2020-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1916132117
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