Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

Patriarchi, Tommaso; Cho, Jounhong Ryan; Merten, Katharina; Howe, Mark W.; Marley, Aaron; Xiong, Wei; Folk, Robert; Broussard, Gerard Joey; Liang, Ruqiang; Jang, Min Jee; Zhong, Haining; Dombeck, Daniel A.; Zastrow, Mark von; Nimmerjahn, Axel; Gradinaru, Viviana; Williams, John T.; Tian, Lin

doi:10.1126/science.aat4422

Cited by 820 publications

(925 citation statements)

References 69 publications

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“…Another limitation is the inability to directly measure the amount of monoamine release as genetically encoded calcium indicators measure axonal activity, which does not necessary correlate with the amount of monoamine release due to release regulation at the presynapse and reuptake by transporters. More recently, engineered monoamine G protein‐coupled receptors (GPCR) have been developed as fluorescent reporters for extracellular monoamine concentration, enabling direct monitoring of released monoamine dynamics in specific brain regions …”

Section: Genetic Tools For the Interrogation Of Dopamine And Serotonimentioning

confidence: 99%

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Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

Yagishita

2019

Psychiatry Clin Neurosci

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Pharmacological studies of antidepressants and atypical antipsychotics have suggested a role of dopamine and serotonin signaling in depression. However, depressive symptoms and treatment effects are difficult to explain based simply on brain‐wide decrease or increase in the concentrations of these molecules. Recent animal studies using advanced neuronal manipulation and observation techniques have revealed detailed dopamine and serotonin dynamics that regulate diverse aspects of motivation‐related behavior. Dopamine and serotonin transiently modulate moment‐to‐moment behavior at timescales ranging from sub‐second to minutes and also produce persistent effects, such as reward‐related learning and stress responses that last longer than several days. Transient and sustained effects often exhibit specific roles depending on the projection sites, where distinct synaptic and cellular mechanisms are required to process the neurotransmitters for each transient and sustained timescale. Therefore, it appears that specific aspects of motivation‐related behavior are regulated by distinct synaptic and cellular mechanisms in specific brain regions that underlie the transient and sustained effects of dopamine and serotonin signaling. Recent clinical studies have implied that subjects with depressive symptoms show impaired transient and sustained signaling functions; moreover, they exhibit heterogeneity in depressive symptoms and neuronal dysfunction. Depressive symptoms may be explained by the dysfunction of each transient and sustained signaling mechanism, and distinct patterns of impairment in the relevant mechanisms may explain the heterogeneity of symptoms. Thus, detailed understanding of dopamine and serotonin signaling may provide new insight into depressive symptoms.

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Section: Genetic Tools For the Interrogation Of Dopamine And Serotonimentioning

confidence: 99%

“…More recently, engineered monoamine G protein-coupled receptors (GPCR) have been developed as fluorescent reporters for extracellular monoamine concentration, enabling direct monitoring of released monoamine dynamics in specific brain regions. 36,37…”

Section: Genetic Tools For the Interrogation Of Dopamine And Serotonimentioning

confidence: 99%

Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

Yagishita

2019

Psychiatry Clin Neurosci

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“…[42] The concentration distribution of dopamine is summarized in Ta ble S2 in the Supporting Information. Moreover,conventional electrochemical methods have been intensively explored for in vivo DA detectioni nt he complex brain environment, [43][44][45][46][47] and they have typically limits of detection no better than nanomo- lar.W ec ompared the sensitivity with these reports (Ta ble S3 in the SupportingI nformation), and found the sensitivity of CN-Ts CuPc PEC system (LOD:2n m)w as uncompromisingly competitive( only al imited number of previousr eports have a better LOD) with additional specific merits, such as high selectivity over other,l ess explored, biologically relevant amines (e.g.,5 -HT). In this regard, the CN-TsCuPc PEC sensing system with an LOD of 2nm would be potentially applicable for in vivo DA detection.…”

Section: Resultsmentioning

confidence: 99%

Exfoliation and Sensitization of 2D Carbon Nitride for Photoelectrochemical Biosensing under Red Light

Zhao

Shen

et al. 2019

Chemistry A European J

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Two-dimensional carbon nitride (CN) has drawn increasinga ttention as ac onjugated metal-free polymer for photoelectrochemical (PEC) biosensing. However,C No nly absorbsu ltraviolet andv ery limited visible light (l < 460 nm), whichp oses potentialr isks for biomolecules and also cannot pass through tissue for in vivo detection. Herein, simultaneousexfoliation and functionalization of CN nanosheets (CNNS) with copper phthalocyanine (TsCuPc) simply by mechanical milling, thanks to the delicate p-p interaction between them,i sr eported. Moreover,d ue to energy-level matching, an effective donor-acceptor (D-A) interaction with much-improved photocurrent underi rradiation with red light (l > 630 nm) was observed for the as-prepared CNNS-Ts CuPc. As an example, dopamine in blood was detected by using red light by aC NNS-TsCuPc photoelectrode with uncompromised linear range and detection limit, as well high selectivity.A so ne of the few successful demonstrations of red-light-responsive PEC sensing systems, this work takes a first step toward future in vivo applicationsb ye nriching the optoelectronic properties of CN with task-specific antenna molecules via D-A interaction.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

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“…Also, it is possible that increased latency to respond observed in the PVD-R may reflect a decrease in motivation. Further studies using more sensitive methods to investigate dopamine release, such as microdialysis in freely moving mice (39), in vivo voltammetry (17), or in vivo dopaminergic fluorescence sensors (103,104), as well as behavioral tasks interrogating motivation would be necessary to determine the influence of dopamine in these VAChTmutant mice.…”

Section: Discussionmentioning

confidence: 99%

Selective decrease of cholinergic signaling from pedunculopontine and laterodorsal tegmental nuclei has little impact on cognition but markedly increases susceptibility to stress

et al. 2019

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The pedunculopontine tegmental nucleus (PPT) and laterodorsal tegmental nucleus (LDT) are heterogeneous brainstem structures that contain cholinergic, glutamatergic, and GABAergic neurons. PPT/LDT neurons are suggested to modulate both cognitive and noncognitive functions, yet the extent to which acetylcholine (ACh) signaling from the PPT/LDT is necessary for normal behavior remains uncertain. We addressed this issue by using a mouse model in which PPT/LDT cholinergic signaling is highly decreased by selective deletion of the vesicular ACh transporter (VAChT) gene. This approach interferes exclusively with ACh signaling, leaving signaling by other neurotransmitters from PPT/LDT cholinergic neurons intact and sparing other cells. VAChT mutants were examined on different PPT/LDT‐associated cognitive domains. Interestingly, VAChT mutants showed no attentional deficits and only minor cognitive flexibility impairments while presenting large deficiencies in both spatial and cued Morris water maze (MWM) tasks. Conversely, working spatial memory determined with the Y‐maze and spatial memory measured with the Barnes maze were not affected, suggesting that deficits in MWM were unrelated to spatial memory abnormalities. Supporting this interpretation, VAChT mutants exhibited alterations in anxiety‐like behavior and increased corticosterone levels after exposure to the MWM, suggesting altered stress response. Thus, PPT/LDT VAChT‐mutant mice present little cognitive impairment per se, yet they exhibit increased susceptibility to stress, which may lead to performance deficits in more stressful conditions.—Janickova, H., Kljakic, O., Rosborough, K., Raulic, S., Matovic, S., Gros, R., Saksida, L. M., Bussey, T. J., Inoue, W., Prado, V. F., Prado, M. A. M. Selective decrease of cholinergic signaling from pedunculopontine and laterodorsal tegmental nuclei has little impact on cognition but markedly increases susceptibility to stress. FASEB J. 33, 7018–7036 (2019). http://www.fasebj.org

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Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

Cited by 820 publications

References 69 publications

Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

Exfoliation and Sensitization of 2D Carbon Nitride for Photoelectrochemical Biosensing under Red Light

Selective decrease of cholinergic signaling from pedunculopontine and laterodorsal tegmental nuclei has little impact on cognition but markedly increases susceptibility to stress

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