scholarly journals Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice

Science ◽  
2021 ◽  
Vol 372 (6540) ◽  
pp. eabe1931 ◽  
Author(s):  
Ashley R. Helseth ◽  
Ricardo Hernandez-Martinez ◽  
Victoria L. Hall ◽  
Matthew L. Oliver ◽  
Brandon D. Turner ◽  
...  

The integrated stress response (ISR) maintains proteostasis by modulating protein synthesis and is important in synaptic plasticity, learning, and memory. We developed a reporter, SPOTlight, for brainwide imaging of ISR state with cellular resolution. Unexpectedly, we found a class of neurons in mouse brain, striatal cholinergic interneurons (CINs), in which the ISR was activated at steady state. Genetic and pharmacological manipulations revealed that ISR signaling was necessary in CINs for normal type 2 dopamine receptor (D2R) modulation. Inhibiting the ISR inverted the sign of D2R modulation of CIN firing and evoked dopamine release and altered skill learning. Thus, a noncanonical, steady-state mode of ISR activation is found in CINs, revealing a neuromodulatory role for the ISR in learning.

2021 ◽  
Vol 2096 (1) ◽  
pp. 012196
Author(s):  
V S Klimash ◽  
B D Tabarov

Abstract The article is devoted to issues related to increasing the energy efficiency of industrial electrothermal installations, both in starting and stationary operating modes due to the use of capacitors and thyristor starters with special control. The results of a significant reduction in the duration of the transient process, elimination of surges and asymmetry of starting currents and voltage drawdowns are presented. The results of full compensation of the reactive power of the network in the steady-state mode are also presented. It is shown that the starting currents do not exceed their steady-state values and that the shutdown of the electrothermal installation is performed without the occurrence of an arc and switching losses at the contacts of the switches. Researches of an electrothermal installation with a capacity of 750 kV⋅A and a voltage of 380 / 80 V are made on the model in the Matlab environment.


Author(s):  
Mor R. Alkaslasi ◽  
Zoe E. Piccus ◽  
Hanna Silberberg ◽  
Li Chen ◽  
Yajun Zhang ◽  
...  

AbstractIn vertebrates, motor control relies on cholinergic neurons in the spinal cord that have been extensively studied over the past hundred years, yet the full heterogeneity of these neurons and their different functional roles in the adult remain to be defined. Here, we developed a targeted single nuclear RNA sequencing approach and used it to identify an array of cholinergic interneurons, visceral and skeletal motor neurons. Our data expose markers for distinguishing these classes of cholinergic neurons and their extremely rich diversity. Specifically, visceral motor neurons, which provide autonomic control, could be divided into more than a dozen transcriptomic classes with anatomically restricted localization along the spinal cord. The complexity of the skeletal motor neurons was also reflected in our analysis with alpha, beta, and gamma subtypes clearly distinguished. In combination, our data provide a comprehensive transcriptomic description of this important population of neurons that control many aspects of physiology and movement and encompass the cellular substrates for debilitating degenerative disorders.


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