Adenosine A2A receptor blockade improves neuroprosthetic learning by volitional control of population calcium signal in M1 cortical neurons

Zhang, Liping; Zhou, Yumin; Li, Chengwei; Zheng, Wu; Yao, Zehan; Wang, Qin; Jin, Yile; Zhang, Shaomin; Chen, Weidong; Chen, Jiang‐Fan

doi:10.1016/j.neuropharm.2020.108250

Cited by 6 publications

(12 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mice were transfected with AAV9‐syn‐GCaMP6f‐WPRE‐SV40 to express the genetically encoded Ca 2+ indicator GCaMP6f in M1 neurons and the calcium fluorescence signal was monitored via a fibre photometry system (Zhang et al., 2020 ). Mice were trained to perform the volitionally controlled neural task at least 85% correct to obtain a reward (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We used an operant volitionally controlled neural task with closed‐loop feedback system by volitional conditioning of population neurons in the M1 cortex by real‐time monitoring of calcium fluorescence signal using a fibre photometry system (the low baseline procedure) (Zhang et al., 2020 ). In the low baseline procedure, the baseline was defined as the lowest F 0 value within a 1 min time window and recalculated for every minute using the lowest F 0 value (Zhang et al., 2020 ). Briefly, mice were transfected with AAV9‐syn‐GCaMP6f‐WPRE‐SV40 to express the genetically encoded Ca 2+ indicator GCaMP6f in M1 neurons and implanted with optical fibres into the same area.…”

Section: Methodsmentioning

confidence: 99%

“…As in our previous study, we performed data analysis in the MatLab platform (Math Works, Natick, MA, USA) with custom-written programs (Zhang et al, 2020).…”

Section: Calcium and Dopamine Fluorescence Signal Analysismentioning

confidence: 99%

See 2 more Smart Citations

Neural representation and modulation of volitional motivation in response to escalating efforts

Zhang

Zhou

et al. 2023

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Task‐dependent volitional control of the selected neural activity in the cortex is critical to neuroprosthetic learning to achieve reliable and robust control of the external device. The volitional control of neural activity is driven by a motivational factor (volitional motivation), which directly reinforces the target neurons via real‐time biofeedback. However, in the absence of motor behaviour, how do we evaluate volitional motivation? Here, we defined the criterion (ΔF/F) of the calcium fluorescence signal in a volitionally controlled neural task, then escalated the efforts by progressively increasing the number of reaching the criterion or holding time after reaching the criterion. We devised calcium‐based progressive threshold‐crossing events (termed ‘Calcium PTE’) and calcium‐based progressive threshold‐crossing holding‐time (termed ‘Calcium PTH’) for quantitative assessment of volitional motivation in response to progressively escalating efforts. Furthermore, we used this novel neural representation of volitional motivation to explore the neural circuit and neuromodulator bases for volitional motivation. As with behavioural motivation, chemogenetic activation and pharmacological blockade of the striatopallidal pathway decreased and increased, respectively, the breakpoints of the ‘Calcium PTE’ and ‘Calcium PTH’ in response to escalating efforts. Furthermore, volitional and behavioural motivation shared similar dopamine dynamics in the nucleus accumbens in response to trial‐by‐trial escalating efforts. In general, the development of a neural representation of volitional motivation may open a new avenue for smooth and effective control of brain–machine interface tasks. Key points Volitional motivation is quantitatively evaluated by M1 neural activity in response to progressively escalating volitional efforts. The striatopallidal pathway and adenosine A2A receptor modulate volitional motivation in response to escalating efforts. Dopamine dynamics encode prediction signal for reward in response to repeated escalating efforts during motor and volitional conditioning. Mice learn to modulate neural activity to compensate for repeated escalating efforts in volitional control.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Neural representation and modulation of volitional motivation in response to escalating efforts

Zhang

Zhou

et al. 2023

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…KW6002 was prepared freshly in 15% DMSO, 15% Castrol oil, and 70% H2O at a final concentration of 0.3 mg/mL, as described previously [8] .…”

Section: Methods Detailsmentioning

confidence: 99%

Optimization of murine retinal mitochondrial injury model

2022

Self Cite

View full text Add to dashboard Cite

“…It has been shown that NMDA receptor activity may be influenced by both A1 and A2A receptor function in schizophrenia models of NMDA receptor hypofunction. While the NMDA antagonist effects in animal models of schizophrenia are reversed by the blockage of A2a receptors and the genetic deletion of the receptor, this suggests that correcting the imbalance in adenosine A2a receptors may rectify the hypofunction of NMDA antagonists [ 167 ].…”

Section: Gpcrs In Cnsmentioning

confidence: 99%

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Rahman

Islam

Mim

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

G protein-coupled receptors (GPCRs) are intricately involved in the conversion of extracellular feedback to intracellular responses. These specialized receptors possess a crucial role in neurological and psychiatric disorders. Most nonsensory GPCRs are active in almost 90% of complex brain functions. At the time of receptor phosphorylation, a GPCR pathway is essentially activated through a G protein signaling mechanism via a G protein-coupled receptor kinase (GRK). Dopamine, an important neurotransmitter, is primarily involved in the pathophysiology of several CNS disorders; for instance, bipolar disorder, schizophrenia, Parkinson’s disease, and ADHD. Since dopamine, acetylcholine, and glutamate are potent neuropharmacological targets, dopamine itself has potential therapeutic effects in several CNS disorders. GPCRs essentially regulate brain functions by modulating downstream signaling pathways. GPR6, GPR52, and GPR8 are termed orphan GPCRs because they colocalize with dopamine D1 and D2 receptors in neurons of the basal ganglia, either alone or with both receptors. Among the orphan GPCRs, the GPR52 is recognized for being an effective psychiatric receptor. Various antipsychotics like aripiprazole and quetiapine mainly target GPCRs to exert their actions. One of the most important parts of signal transduction is the regulation of G protein signaling (RGS). These substances inhibit the activation of the G protein that initiates GPCR signaling. Developing a combination of RGS inhibitors with GPCR agonists may prove to have promising therapeutic potential. Indeed, several recent studies have suggested that GPCRs represent potentially valuable therapeutic targets for various psychiatric disorders. Molecular biology and genetically modified animal model studies recommend that these enriched GPCRs may also act as potential therapeutic psychoreceptors. Neurotransmitter and neuropeptide GPCR malfunction in the frontal cortex and limbic-related regions, including the hippocampus, hypothalamus, and brainstem, is likely responsible for the complex clinical picture that includes cognitive, perceptual, emotional, and motor symptoms. G protein and GPCR-mediated signaling play a critical role in developing new treatment options for mental health issues, and this study is aimed at offering a thorough picture of that involvement. For patients who are resistant to current therapies, the development of new drugs that target GPCR signaling cascades remains an interesting possibility. These discoveries might serve as a fresh foundation for the creation of creative methods for pharmacologically useful modulation of GPCR function.

show abstract

Adenosine A2A receptor blockade improves neuroprosthetic learning by volitional control of population calcium signal in M1 cortical neurons

Cited by 6 publications

References 62 publications

Neural representation and modulation of volitional motivation in response to escalating efforts

Neural representation and modulation of volitional motivation in response to escalating efforts

Optimization of murine retinal mitochondrial injury model

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Contact Info

Product

Resources

About