scholarly journals A cholinergic medial septum input to medial habenula mediates generalization formation and extinction of visual aversion

2021 ◽  
Author(s):  
Rong-Hao Mu ◽  
Xiao-Meng Han ◽  
Hao Wang ◽  
Su-Su Tang ◽  
Yan Long ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Affective Disorders ◽  
Cholinergic Neurons ◽  
Medial Septum ◽  
Glutamatergic Neurons ◽  
Medial Habenula ◽  
Underlying Mechanisms ◽  
Α7 Nachrs

Abstract Generalization formation and extinction of aversion are associated with affective disorders, but little is known about underlying mechanisms. Here, we established a novel procedure for induction of visual aversion by dynamic stripe images on digital screens in mice. We found that decreased activity of medial septum (MS) cholinergic neurons led to generalization aversion loss, but didn’t affect its extinction. We identified a new projection from MS cholinergic neurons to medial habenula (MHb), and found that inhibiting MS→MHb cholinergic circuit disrupts generalization formation, while activating this circuit damages extinction. The further studies showed that blockade of M1 mAChRs rather than α4β2 and α7 nAChRs on downstream glutamatergic neurons that corelease glutamate and acetylcholine blunted generalization enhancement and extinction deficit caused by activation of MS→MHb circuits. These findings reveal that MS→MHb cholinergic circuit modulates generalization formation and extinction of aversion, providing new insights on affective disorders such as PTSD and anxiety disorders.

Dispositional negativity, cognition, and anxiety disorders: An integrative translational neuroscience framework

2019 ◽  
Author(s):  
Juyoen Hur ◽  
Melissa D. Stockbridge ◽  
Andrew S. Fox ◽  
Alexander J. Shackman
Keyword(s):  
Risk Factor ◽  
Anxiety Disorders ◽  
Executive Control ◽  
Intervention Strategies ◽  
Attentional Biases ◽  
Translational Neuroscience ◽  
Adult Personality ◽  
Fundamental Dimension ◽  
To Come ◽  
Underlying Mechanisms

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the underlying mechanisms have only recently begun to come into focus. Here, we review new insights into the nature and biological bases of dispositional negativity, a fundamental dimension of childhood temperament and adult personality and a prominent risk factor for the development of pediatric and adult anxiety disorders. Converging lines of epidemiological, neurobiological, and mechanistic evidence suggest that dispositional negativity increases the likelihood of psychopathology via specific neurocognitive mechanisms, including attentional biases to threat and deficits in executive control. Collectively, these observations provide an integrative translational framework for understanding the development and maintenance of anxiety disorders in adults and youth and set the stage for developing improved intervention strategies.

scholarly journals Crucial Role of FABP3 in αSyn-Induced Reduction of Septal GABAergic Neurons and Cognitive Decline in Mice

2021 ◽  
Vol 22 (1) ◽  
pp. 400
Author(s):  
Kazuya Matsuo ◽  
Yasushi Yabuki ◽  
Ronald Melki ◽  
Luc Bousset ◽  
Yuji Owada ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Processing ◽  
Dopaminergic Neurons ◽  
Dorsal Striatum ◽  
Cholinergic Neurons ◽  
Medial Septum ◽  
Gabaergic Neurons ◽  
Gamma Aminobutyric Acid ◽  
Fatty Acid Binding

In synucleinopathies, while motor symptoms are thought to be attributed to the accumulation of misfolded α-synuclein (αSyn) in nigral dopaminergic neurons, it remains to be elucidated how cognitive decline arises. Here, we investigated the effects of distinct αSyn strains on cognition and the related neuropathology in the medial septum/diagonal band (MS/DB), a key region for cognitive processing. Bilateral injection of αSyn fibrils into the dorsal striatum potently impaired cognition in mice. The cognitive decline was accompanied by accumulation of phosphorylated αSyn at Ser129 and reduction of gamma-aminobutyric acid (GABA)-ergic but not cholinergic neurons in the MS/DB. Since we have demonstrated that fatty acid-binding protein 3 (FABP3) is critical for αSyn neurotoxicity in nigral dopaminergic neurons, we investigated whether FABP3 also participates in αSyn pathology in the MS/DB and cognitive decline. FABP3 was highly expressed in GABAergic but rarely in cholinergic neurons in the MS/DB. Notably, Fabp3 deletion antagonized the accumulation of phosphorylated αSyn, decrease in GABAergic neurons, and cognitive impairment caused by αSyn fibrils. Overall, the present study indicates that FABP3 mediates αSyn neurotoxicity in septal GABAergic neurons and the resultant cognitive impairment, and that FABP3 in this subpopulation could be a therapeutic target for dementia in synucleinopathies.

Medial septum glutamatergic neurons control wakefulness through a septo-hypothalamic circuit

2021 ◽  
Author(s):  
Shuming An ◽  
Haiyan Sun ◽  
Miao Wu ◽  
Danfeng Xie ◽  
Su-Wan Hu ◽  
...  
Keyword(s):  
Medial Septum ◽  
Glutamatergic Neurons

scholarly journals Disruption of VGLUT1 in cholinergic medial habenula projections increases nicotine self-administration

2021 ◽  
Author(s):  
Elizabeth A Souter ◽  
Yen-Chu Chen ◽  
Vivien Zell ◽  
Valeria Lallai ◽  
Thomas Steinkellner ◽  
...  
Keyword(s):  
Cholinergic Neurons ◽  
Nicotine Addiction ◽  
Conditional Knockout ◽  
Self Administration ◽  
Interpeduncular Nucleus ◽  
Medial Habenula ◽  
Field Assay ◽  
Nicotine Consumption ◽  
Additional Support ◽  
Cholinergic Projections

Cholinergic projections from the medial habenula (MHb) to the interpeduncular nucleus (IPN) have been studied for their complex contributions to nicotine addiction and have been implicated in nicotine reinforcement, aversion, and withdrawal. While it has been established that MHb cholinergic projections co-release glutamate, no direct evidence has demonstrated a role for this specific glutamate projection in nicotine consumption. In the present study, a novel floxed Slc17a7 (VGLUT1) mouse was generated and used to create conditional knockout (cKO) mice that lack VGLUT1 in MHb cholinergic neurons. Histochemical approaches and optogenetics-assisted electrophysiology were used to validate the disruption of VGLUT1 from cholinergic MHb to IPN projections. The mice displayed no gross phenotypic abnormalities and exhibited normal exploratory and locomotor behavior in the open-field assay. However, the loss of VGLUT1-mediated glutamate co-release led to increased nicotine self-administration. These findings indicate that glutamate co-release from ventral MHb cholinergic neurons opposes nicotine consumption and provide additional support for targeting this synapse to develop potential treatments to nicotine addiction.

Everyday creativity and bipolar and unipolar affective disorder: preliminary study of personal and family history

1992 ◽  
Vol 7 (2) ◽  
pp. 49-52 ◽  
Author(s):  
R Richards ◽  
DK Kinney ◽  
H Daniels ◽  
K Linkins
Keyword(s):  
Bipolar Disorder ◽  
Family History ◽  
Affective Disorder ◽  
Affective Disorders ◽  
Bipolar Disorders ◽  
Data Support ◽  
History Of ◽  
Preliminary Study ◽  
Everyday Creativity ◽  
Underlying Mechanisms

SummaryPreliminary new data support the enhancement of ‘everyday’ creativity among those persons with bipolar disorders who manifest milder rather than more severe mood elevations, and among certain individuals who are likely to carry bipolar liability but themselves show no clinical mood elevations – in this case, unipolar depressives with a family history of bipolar disorder, when compared with depressives lacking this history. Creativity was assessed using the lifetime creativity scales (Richards el al, 1988). Underlying mechanisms may be multifactorial and complex. Results suggest that both personal and family history should be considered when making predictions concerning creativity and affective disorders.

scholarly journals Nurr1, Pitx3, and α7 nAChRs mRNA Expression in Nigral Tissue of Rats with Pedunculopontine Neurotoxic Lesion

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 616 ◽  
Author(s):  
Blanco-Lezcano ◽  
Alberti-Amador ◽  
González-Fraguela ◽  
Larrea ◽  
Pérez-Serrano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Cholinergic Neurons ◽  
Pedunculopontine Nucleus ◽  
Adult Brain ◽  
Related Factor ◽  
Nicotinic Cholinergic Receptors ◽  
Neurotoxic Lesion ◽  
Nigral Degeneration ◽  
Α7 Nachrs

Background and Objectives: The knowledge that the cholinergic neurons from pedunculopontine nucleus (PPN) are vulnerable to the degeneration in early stages of the Parkinson disease progression has opened new perspectives to the development of experimental model focused in pontine lesions that could increase the risk of nigral degeneration. In this context it is known that PPN lesioned rats exhibit early changes in the gene expression of proteins responsible for dopaminergic homeostasis. At the same time, it is known that nicotinic cholinergic receptors (nAChRs) mediate the excitatory influence of pontine-nigral projection. However, the effect of PPN injury on the expression of transcription factors that modulate dopaminergic neurotransmission in the adult brain as well as the α7 nAChRs gene expression has not been studied. The main objective of the present work was the study of the effects of the unilateral neurotoxic lesion of PPN in nuclear receptor-related factor 1 (Nurr1), paired-like homeodomain transcription factor 3 (Pitx3), and α7 nAChRs mRNA expression in nigral tissue. Materials and Methods: The molecular biology studies were performed by means of RT-PCR. The following experimental groups were organized: Non-treated rats, N-methyl-D-aspartate (NMDA)-lesioned rats, and Sham operated rats. Experimental subjects were sacrificed 24 h, 48 h and seven days after PPN lesion. Results: Nurr1 mRNA expression, showed a significant increase both 24 h (p < 0.001) and 48 h (p < 0.01) after PPN injury. Pitx3 mRNA expression evidenced a significant increase 24 h (p < 0.001) followed by a significant decrease 48 h and seven days after PPN lesion (p < 0.01). Finally, the α7 nAChRs nigral mRNA expression remained significantly diminished 24 h, 48 h (p < 0.001), and 7 days (p < 0.01) after PPN neurotoxic injury. Conclusion: Taking together these modifications could represent early warning signals and could be the preamble to nigral neurodegeneration events.

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