scholarly journals A Cholinergic Medial Septum Input to Medial Habenula Mediates Generalization Formation and Extinction of Visual Aversion

2021 ◽  
Author(s):  
Ronghao Mu ◽  
Susu Tang ◽  
Xiaomeng Han ◽  
Hao Wang ◽  
Danhua Yuan ◽  
...  
2021 ◽  
Author(s):  
Rong-Hao Mu ◽  
Xiao-Meng Han ◽  
Hao Wang ◽  
Su-Su Tang ◽  
Yan Long ◽  
...  

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.


2020 ◽  
Author(s):  
Hajime Shiotani ◽  
Muneaki Miyata ◽  
Takeshi Kameyama ◽  
Kenji Mandai ◽  
Miwako Yamasaki ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
pp. 400
Author(s):  
Kazuya Matsuo ◽  
Yasushi Yabuki ◽  
Ronald Melki ◽  
Luc Bousset ◽  
Yuji Owada ◽  
...  

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Yi ◽  
Tavita Garrett ◽  
Karl Deisseroth ◽  
Heikki Haario ◽  
Emily Stone ◽  
...  

AbstractParvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca ($$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB ) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. We combined electrophysiological, optogenetic, and modeling approaches to investigate $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB neuronal properties. $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB neurons had intrinsic membrane properties distinct from acetylcholine- and somatostatin-containing MS-DBB subtypes. Viral expression of the fast-kinetic channelrhodopsin ChETA-YFP elicited action potentials to brief (1–2 ms) 470 nm light pulses. To investigate $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB transmission, light pulses at 5–50 Hz frequencies generated trains of inhibitory postsynaptic currents (IPSCs) in CA1 stratum oriens interneurons. Using a similar approach, optogenetic activation of local hippocampal PV ($$\hbox {PV}_{\text{HC}}$$ PV HC ) neurons generated trains of $$\hbox {PV}_{\text{HC}}$$ PV HC -mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, relative to $$\hbox {PV}_{\text{HC}}$$ PV HC synapses, $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB synapses possessed lower initial release probability, transiently resisted STD at gamma (20–50 Hz) frequencies, and recovered more rapidly from synaptic depression. Experimentally-constrained mathematical synapse models explored mechanistic differences. Relative to the $$\hbox {PV}_{\text{HC}}$$ PV HC model, the $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of $$\hbox {PV}_{\text{MS-DBB}}$$ PV MS-DBB synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus.


1992 ◽  
Vol 17 ◽  
pp. 61 ◽  
Author(s):  
Masashi Tsurusaki ◽  
Takashi Akasu ◽  
Joel P. Gallacher

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

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