The medial habenula and interpeduncular nucleus circuitry is critical in addiction, anxiety, and mood regulation

McLaughlin, Ian; Dani, John A.; Biasi, Mariella De

doi:10.1111/jnc.14008

Cited by 149 publications

(125 citation statements)

References 144 publications

Supporting

Mentioning

119

Contrasting

Order By: Relevance

“…The cFb activation of the IPN by nicotine confirms the findings of several research groups (Lanca et al, ; McLaughlin et al, ; Pang et al, ; Ren et al, ; Salas et al, ; Salminen et al, ; Seppa et al, ). Nicotine stimulates presynaptic glutamate release and somatic calcium responses in the IPN (Girod, Barazangi, McGehee, & Role, ; McGehee, Heath, Gelber, Devay, & Role, ) similar to its effects in the VTA (Girod & Role, ; Mansvelder et al, ).…”

Section: Discussionsupporting

confidence: 82%

“…The cFb activation of the IPN by nicotine confirms the findings of several research groups (Lanca et al, 2000b;McLaughlin et al, 2017;Pang et al, 1993;Ren et al, 1992;Salas et al, 2009;Salminen et al, 2000;Seppa et al, 2001 1995) similar to its effects in the VTA (Girod & Role, 2001;Mansvelder et al, 2000). IPN activity has been shown to inhibit dopaminergic VTA neurons (Nishikawa, Fage, & Scatton, 1986).…”

Section: The Role Of Ipn Mt Ptg and Ldtg Cfb Ensembles In Nicotinsupporting

confidence: 85%

“…The interpeduncular nucleus (IPN) is a primarily GABAergic nucleus located medial to the VTA (Hemmendinger & Moore, 1984) and interconnected with multiple hind-mid-and forebrain regions (Aizawa, Kobayashi, Tanaka, Fukai, & Okamoto, 2012;Antolin-Fontes, Ables, Gorlich, & Ibanez-Tallon, 2015;Hemmendinger & Moore, 1984;Morley, 1986;Vertes & Fass, 1988;Woolf & Butcher, 1985). The IPN also shows cFb activation in response to a single dose of nicotine (Lanca et al, 2000b;Pang et al, 1993;Ren et al, 1992;Seppa, Salminen, Moed, & Ahtee, 2001) or chronic nicotine administration (Salminen, Seppa, Gaddnas, & Ahtee, 2000) and is thought to play an important role in nicotine withdrawal (McLaughlin, Dani, & De Biasi, 2017;Molas, DeGroot, Zhao-Shea, & Tapper, 2017;Salas, Sturm, Boulter, & De Biasi, 2009).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

c‐Fos marking of identified midbrain neurons coactive after nicotine administration in‐vivo

Baur

Hach

Bernardi

et al. 2018

J of Comparative Neurology

View full text Add to dashboard Cite

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. We performed double immunohistochemistry for the immediate early gene and surrogate activity sensor, c-Fos, and markers for either cholinergic, dopaminergic or GABAergic cell types in mice treated with nicotine. Both acute (0.5 mg/kg) and chronic (0.5 mg/kg/day for 7 days) nicotine strongly activated GABAergic neurons of the interpeduncular nucleus and medial terminal nucleus of the accessory optic tract (MT). Acute but not chronic nicotine also activated small percentages of dopaminergic and other neurons in the ventral tegmental area (VTA) as well as noncholinergic neurons in the pedunculotegmental and laterodorsal tegmental nuclei (PTg/LDTg). Twenty four hours of nicotine withdrawal after chronic nicotine treatment suppressed c-Fos activation in the MT. In comparison to nicotine, a single dose of cocaine caused a similar activation in the PTg/LDTg but not the VTA where GABAergic cells were strongly activated but dopaminergic neurons were not affected. These results indicate the existence of drug of abuse specific ensembles. The loss of ensemble activation in the VTA and PTg/LDTg after chronic nicotine represents a molecular and cellular tolerance which may have implications for the mechanisms underlying nicotine dependence.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: The Role Of Ipn Mt Ptg and Ldtg Cfb Ensembles In Nicotinsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

c‐Fos marking of identified midbrain neurons coactive after nicotine administration in‐vivo

Baur

Hach

Bernardi

et al. 2018

J of Comparative Neurology

View full text Add to dashboard Cite

show abstract

“…the IPN, a major downstream target of the mHb [42]. Therefore, we examined the neuronal activity of the IPN in TMEM16A cKO and control mice by staining for c-Fos, an immediate early gene product ( Fig 4A and B).…”

Section: Reduced Activity Of Ipn Neurons In Tmem16a Cko Micementioning

confidence: 99%

TMEM16A expression in cholinergic neurons of the medial habenula mediates anxiety‐related behaviors

et al. 2019

View full text Add to dashboard Cite

TMEM16A, a Ca 2+ -activated Cl À channel, is known to modulate the excitability of various types of cells; however, its function in central neurons is largely unknown. Here, we show the specific expression of TMEM16A in the medial habenula (mHb) via RNAscope in situ hybridization, immunohistochemistry, and electrophysiology. When TMEM16A is ablated in the mHb cholinergic neurons (TMEM16A cKO mice), the slope of after-hyperpolarization of spontaneous action potentials decreases and the firing frequency is reduced. Reduced mHb activity also decreases the activity of the interpeduncular nucleus (IPN). Moreover, TMEM16A cKO mice display anxiogenic behaviors and deficits in social interaction without despair-like phenotypes or cognitive dysfunctions. Finally, chemogenetic inhibition of mHb cholinergic neurons using the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) approach reveals similar behavioral phenotypes to those of TMEM16A cKO mice. We conclude that TMEM16A plays a key role in anxiety-related behaviors regulated by mHb cholinergic neurons and could be a potential therapeutic target against anxiety-related disorders.Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature 537: 97 -101 ª 2019 The Authors EMBO reports 21: e48097 | 2020

show abstract

“…Circos plot analysis of curated functional and anatomical research ( Figure 2) and 3D tracing experiments ((Oh et al, 2014), Video S1) demonstrate a wide-spread influence of cholinergic systems on both rudimentary and higher cognitive processes throughout the entire mammalian brain (Woolf, 1991;Bina et al, 1993;Sarter et al, 2009;Mesulam, 2013;Luchicchi et al, 2014;Eskow Jaunarajs et al, 2015;Gonzales and Smith, 2015;Lin et al, 2015;Ballinger et al, 2016;Herman et al, 2016;Prado et al, 2017;Haam and Yakel, 2017;McLaughlin et al, 2017). However, trophic factor dependency has only been proven for basal forebrain projection neurons Ch1-Ch4, leaving many open questions about the nature of cholinergic interneurons in the striatum and cortex (Mufson et al, 2009) and their transcriptomic features.…”

Section: Cholinergic Systems In the Cnsmentioning

confidence: 99%

Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder

Lobentanzer

Hanin

Klein

et al. 2019

Preprint

View full text Add to dashboard Cite

135 words): RNA-sequencing analyses are often limited to identifying lowest p-value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA-sequencing of human male-and female-originated cell lines, and connectomics of transcription factor-and microRNA-interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. While these pathologies show massive transcriptional parallels, their clinically well-known sexual dimorphisms remain unexplained. Our method explicates the differences between afflicted men and women, and identifies diseaseaffected pathways of cholinergic transmission and gp130-family neurokine controllers of immune function, interlinked by microRNAs. This approach may open new perspectives for seeking biomarkers and therapeutic targets, also in other transmitter systems and diseases.Manuscript (Erta et al., 2012): the gp130 co-receptor (also known as IL6ST, IL-6 signal transducer), and the LIF-receptor. Gp130-family neurokines unite properties of neurotrophic (e.g. on dopaminergic neurons) and immunogenic nature, both prominent facets in the molecular etiology of SCZ and BD (Harrison, 2015) and in cholinergic signaling (Stanke et al., 2006). Neurokines can activate JAK1/2, TYK2 and STAT1/3/5A/5B (Rawlings, 2004), affecting neurotransmission as well as immunity. However, to the best of our knowledge, their roles in SCZ/BD were not yet studied.SCZ/BD hallmarks also involve circadian perturbations. The cholinergic-catecholaminergic imbalance in BD (Van Enkhuizen et al., 2015) follows variable transcriptionally-regulated rhythms (e.g. CLOCK, ARNTL, RORA), and affected individuals exhibit decreased REM latency (the duration from onset of sleep to the first rapid eye movement phase) and increased vulnerability for disease that can be modulated by muscarinic agonists/antagonists (Ising et al., 2005). Correspondingly, the muscarinic M1/M3 receptor genes are essential for REM sleep (Niwa et al., 2018), and sleep deprivation exerts short-term antidepressant effects (Wu and Bunney, 1990), reduced cortical ACh levels (Boonstra et al., 2007), and vast transcriptional changes in basal forebrain cholinergic neurons (Nikonova et al., 2017).The quantitative measurement of disease-relevance of individual perturbed genes is a common methodological problem in transcriptomic analyses. To reduce complexity, transcripts are often filtered by their p-values, leading to bias towards few highly expressed and differentially regulated genes. This does not agree with a polygenic model where each component contributes a small effect. To alleviate this bias while still attempting the necessary complexity reduction, we developed an integrative approach of multiple perspectives. Jerusalem and Andreas Meisel, Berlin and to Dr. Ester Bennett, Jerusalem ...

show abstract

The medial habenula and interpeduncular nucleus circuitry is critical in addiction, anxiety, and mood regulation

Cited by 149 publications

References 144 publications

c‐Fos marking of identified midbrain neurons coactive after nicotine administration in‐vivo

c‐Fos marking of identified midbrain neurons coactive after nicotine administration in‐vivo

TMEM16A expression in cholinergic neurons of the medial habenula mediates anxiety‐related behaviors

Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder

Contact Info

Product

Resources

About