Dissecting the brain with spatially resolved multi-omics

Journal of Pharmaceutical Analysis, Journal Year: 2023, Volume and Issue: 13(7), P. 694 - 710

Published: April 10, 2023

Recent studies have highlighted spatially resolved multi-omics technologies, including spatial genomics, transcriptomics, proteomics, and metabolomics, as powerful tools to decipher the heterogeneity of brain. Here, we focus on two major approaches in transcriptomics (next-generation sequencing-based technologies image-based technologies), mass spectrometry imaging used proteomics metabolomics. Furthermore, discuss their applications neuroscience, building brain atlas, uncovering gene expression patterns neurons for special behaviors, deciphering molecular basis neuronal communication, providing a more comprehensive explanation mechanisms underlying central nervous system disorders. However, further efforts are still needed toward integrative application real-time analysis living cells, detailed profile whole-brain view, combination functional verification.

Language: Английский

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Deep self-learning enables fast, high-fidelity isotropic resolution restoration for volumetric fluorescence microscopy

Light Science & Applications, Journal Year: 2023, Volume and Issue: 12(1)

Published: Aug. 28, 2023

One intrinsic yet critical issue that troubles the field of fluorescence microscopy ever since its introduction is unmatched resolution in lateral and axial directions (i.e., anisotropy), which severely deteriorates quality, reconstruction, analysis 3D volume images. By leveraging natural anisotropy, we present a deep self-learning method termed Self-Net significantly improves images by using from same raw dataset as rational targets. incorporating unsupervised learning for realistic anisotropic degradation supervised high-fidelity isotropic recovery, our can effectively suppress hallucination with substantially enhanced image quality compared to previously reported methods. In experiments, show reconstruct organelle tissue levels via various platforms, e.g., wide-field, laser-scanning, or super-resolution microscopy. For first time, enables whole-brain imaging at voxel 0.2 × μm3, addresses last-mile problem data single-neuron morphology visualization reconstruction minimal effort cost. Overall, promising approach overcoming inherent anisotropy all classes

Language: Английский

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Ventral pallidal regulation of motivated behaviors and reinforcement

Frontiers in Neural Circuits, Journal Year: 2023, Volume and Issue: 17

Published: Feb. 2, 2023

The interconnected nuclei of the ventral basal ganglia have long been identified as key regulators motivated behavior, and dysfunction this circuit is strongly implicated in mood substance use disorders. pallidum (VP) a central node ganglia, recent studies revealed complex VP cellular heterogeneity cell- circuit-specific regulation reward, aversion, motivation, drug-seeking behaviors. Although canonically considered relay output structure for circuit, emerging data indicate that hub an extensive network reward processing motivation extends beyond classically defined borders. neurons respond temporally faster show more advanced coding prediction error than upstream nucleus accumbens, regulate activity mesencephalon dopamine system. This review will summarize findings literature provide update on behaviors reinforcement by with specific focus In addition, we discuss mechanisms which stress drug exposure alter functioning produce susceptibility to neuropsychiatric Lastly, outline unanswered questions identify future directions necessary further clarify role Significance: Research last decade has Novel insights obtained using interrogation strategies led major shift our understanding region. Here, comprehensive integrate novel existing highlight linchpin neural systems aversion. animal models

Language: Английский

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Error-related signaling in nucleus accumbens D2 receptor-expressing neurons guides inhibition-based choice behavior in mice

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 21, 2023

Abstract Learned associations between environmental cues and the outcomes they predict (cue-outcome associations) play a major role in behavioral control, guiding not only which responses we should perform, but also inhibit, order to achieve specific goal. The encoding of such cue-outcome associations, as well performance cue-guided choice behavior, is thought involve dopamine D1 D2 receptor-expressing medium spiny neurons (D1-/D2-MSNs) nucleus accumbens (NAc). Here, using visual discrimination task male mice, assessed NAc D1-/D2-MSNs inhibition inappropriate responding. Cell-type neuronal silencing in-vivo imaging revealed D2-MSNs contribute inhibiting responses, with activation following response errors playing an important optimizing future behavior. Our findings indicate that error-signaling by contributes ability use inhibit

Language: Английский

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Ongoing movement controls sensory integration in the dorsolateral striatum

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 22, 2023

Abstract The dorsolateral striatum (DLS) receives excitatory inputs from both sensory and motor cortical regions. In the neocortex, responses are affected by activity, however, it is not known whether such sensorimotor interactions occur in how they shaped dopamine. To determine impact of activity on striatal processing, we performed vivo whole-cell recordings DLS awake mice during presentation tactile stimuli. Striatal medium spiny neurons (MSNs) were activated whisker stimulation spontaneous whisking, their to deflection ongoing whisking attenuated. Dopamine depletion reduced representation direct-pathway MSNs, but those indirect-pathway. Furthermore, dopamine impaired discrimination between ipsilateral contralateral direct indirect pathway MSNs. Our results show that affects processes dopamine- cell type-dependent.

Language: Английский

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