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ACS Sensors Jun 2024Raman spectroscopy has become an important single-cell analysis tool for monitoring biochemical changes at the cellular level. However, Raman spectral data, typically...
Raman spectroscopy has become an important single-cell analysis tool for monitoring biochemical changes at the cellular level. However, Raman spectral data, typically presented as continuous data with high-dimensional characteristics, is distinct from discrete sequences, which limits the application of deep learning-based algorithms in data analysis due to the lack of discretization. Herein, a model called fragment-fusion transformer is proposed, which integrates the discrete fragmentation of continuous spectra based on their intrinsic characteristics with the extraction of intrafragment features and the fusion of interfragment features. The model integrates the intrinsic feature-based fragmentation of spectra with transformer, constructing the fragment transformer block for feature extraction within fragments. Interfragment information is combined through the pyramid design structure to improve the model's receptive field and fully exploit the spectral properties. During the pyramidal fusion process, the information gain of the final extracted features in the spectrum has been enhanced by a factor of 9.24 compared to the feature extraction stage within the fragment, and the information entropy has been enhanced by a factor of 13. The fragment-fusion transformer achieved a spectral recognition accuracy of 94.5%, which is 4% higher compared to the method without fragmentation and fusion processes on the test set of cell Raman spectroscopy identification experiments. In comparison to common spectral classification models such as KNN, SVM, logistic regression, and CNN, fragment-fusion transformer has achieved 4.4% higher accuracy than the best-performing CNN model. Fragment-fusion transformer method has the potential to serve as a general framework for discretization in the field of continuous spectral data analysis and as a research tool for analyzing the intrinsic information within spectra.
PubMed: 38934798
DOI: 10.1021/acssensors.4c00149 -
Inorganic Chemistry Jun 2024Metal halide perovskites with a two-dimensional structure are utilized in photovoltaics and optoelectronics. High-crystallinity CsSnBr specimens have been synthesized...
Metal halide perovskites with a two-dimensional structure are utilized in photovoltaics and optoelectronics. High-crystallinity CsSnBr specimens have been synthesized via ball milling. Differential scanning calorimetry curves show melting at 553 K (endothermic) and recrystallization at 516 K (exothermic). Structural analysis using synchrotron X-ray diffraction data, collected from 100 to 373 K, allows for the determination of Debye model parameters. This analysis provides insights into the relative Cs-Br and Sn-Br chemical bonds within the tetragonal structure (space group: 4/), which remains stable throughout the temperature range studied. Combined with neutron data, X-N techniques permit the identification of the Sn lone electron pair (5s) in the two-dimensional framework, occupying empty space opposite to the four Sn-Br bonds of the pyramidal [SnBr] coordination polyhedra. Additionally, diffuse reflectance UV-vis spectroscopy unveils an indirect optical gap of approximately ∼3.3 eV, aligning with the calculated value from the -DFT method (∼3.2 eV). The material exhibits a positive Seebeck coefficient as high as 6.5 × 10 μV K at 350 K, which evolves down to negative values of -3.0 × 10 μV K at 550 K, surpassing values reported for other halide perovskites. Notably, the thermal conductivity remains exceptionally low, between 0.32 and 0.25 W m K.
PubMed: 38920333
DOI: 10.1021/acs.inorgchem.4c01861 -
Proceedings of the National Academy of... Jul 2024Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly...
Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of () in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly. In both humans and mice, is highly expressed in ciliated radial glia of the fetal ventricular-subventricular zone as well as in their postnatal ependymal and neuronal progeny. The ventriculomegaly observed in mice is associated with disrupted primary cilia and ependymal planar cell polarity that results in impaired cilia-generated CSF flow. Further, prefrontal pyramidal neurons in ventriculomegalic Δ mice exhibit decreased excitatory drive and reduced high-frequency firing. Consistent with these findings in mice, we identified rare, damaging heterozygous germline variants in in five unrelated patients with neurosurgically treated CH and comorbid ASD or other neurodevelopmental disorders. Mice engineered with the orthologous ASD-associated KATNAL2 F244L missense variant recapitulated the ventriculomegaly found in human patients. Together, these data suggest pathogenic variants alter intraventricular CSF homeostasis and parenchymal neuronal connectivity by disrupting microtubule dynamics in fetal radial glia and their postnatal ependymal and neuronal descendants. The results identify a molecular mechanism underlying the development of ventriculomegaly in a genetic subset of patients with ASD and may explain persistence of neurodevelopmental phenotypes in some patients with CH despite neurosurgical CSF shunting.
Topics: Animals; Hydrocephalus; Humans; Mice; Microtubules; Male; Cilia; Female; Katanin; Autism Spectrum Disorder; Neurons; Ependyma; ATPases Associated with Diverse Cellular Activities; Pyramidal Cells
PubMed: 38916997
DOI: 10.1073/pnas.2314702121 -
BioRxiv : the Preprint Server For... Jun 2024In medial prefrontal cortex (mPFC), fast-spiking parvalbumin (PV) interneurons regulate excitability and microcircuit oscillatory activity important for cognition....
UNLABELLED
In medial prefrontal cortex (mPFC), fast-spiking parvalbumin (PV) interneurons regulate excitability and microcircuit oscillatory activity important for cognition. Although PV interneurons inhibit pyramidal neurons, they themselves express δ subunits of GABAA receptors important for slow inhibition. However, the specific contribution of δ-containing GABAA receptors to the function of PV interneurons in mPFC is unclear. We explored cellular, synaptic, and local-circuit activity in PV interneurons and pyramidal neurons in mouse mPFC after selectively deleting δ subunits in PV interneurons (cKO mice). In current-clamp recordings, cKO PV interneurons exhibited a higher frequency of action potentials and higher input resistance than wild type (WT) PV interneurons. Picrotoxin increased firing and GABA decreased firing in WT PV interneurons but not in cKO PV interneurons. The δ-preferring agonist THIP reduced spontaneous inhibitory postsynaptic currents in WT pyramidal neurons but not in cKO pyramidal neurons. In WT slices, depolarizing the network with 400 nM kainate increased firing of pyramidal neurons but had little effect on PV interneuron firing. By contrast, in cKO slices kainate recruited PV interneurons at the expense of pyramidal neurons. At the population level, kainate induced broadband increases in local field potentials in WT but not cKO slices. These results on cells and the network can be understood through increased excitability of cKO PV interneurons. In summary, our study demonstrates that δ-containing GABAA receptors in mPFC PV interneurons play a crucial role in regulating their excitability and the phasic inhibition of pyramidal neurons, elucidating intricate mechanisms governing cortical circuitry.
SIGNIFICANCE STATEMENT
By selectively deleting δ-containing GABAA receptors in PV interneurons, we demonstrate the importance of these receptors on PV interneuron excitability, synaptic inhibition of pyramidal neurons, and circuit function.
PubMed: 38915641
DOI: 10.1101/2024.06.14.599033 -
BioRxiv : the Preprint Server For... Jun 2024In schizophrenia, layer 3 pyramidal neurons (L3PNs) in the dorsolateral prefrontal cortex (DLPFC) are thought to receive fewer excitatory synaptic inputs and to have...
UNLABELLED
In schizophrenia, layer 3 pyramidal neurons (L3PNs) in the dorsolateral prefrontal cortex (DLPFC) are thought to receive fewer excitatory synaptic inputs and to have lower expression levels of activity-dependent genes and of genes involved in mitochondrial energy production. In concert, these findings from previous studies suggest that DLPFC L3PNs are hypoactive in schizophrenia, disrupting the patterns of activity that are crucial for working memory, which is impaired in the illness. However, whether lower PN activity produces alterations in inhibitory and/or excitatory synaptic strength has not been tested in the primate DLPFC. Here, we decreased PN excitability in rhesus monkey DLPFC using adeno-associated viral vectors (AAVs) to produce Cre recombinase-mediated overexpression of Kir2.1 channels, a genetic silencing tool that efficiently decreases neuronal excitability. In acute slices prepared from DLPFC 7-12 weeks post-AAV microinjections, Kir2.1-overexpressing PNs had a significantly reduced excitability largely attributable to highly specific effects of the AAV-encoded Kir2.1 channels. Moreover, recordings of synaptic currents showed that Kir2.1-overexpressing DLPFC PNs had reduced strength of excitatory synapses whereas inhibitory synaptic inputs were not affected. The decrease in excitatory synaptic strength was not associated with changes in dendritic spine number, suggesting that excitatory synapse quantity was unaltered in Kir2.1-overexpressing DLPFC PNs. These findings suggest that, in schizophrenia, the excitatory synapses on hypoactive L3PNs are weaker and thus might represent a substrate for novel therapeutic interventions.
SIGNIFICANCE STATEMENT
In schizophrenia, dorsolateral prefrontal cortex (DLPFC) pyramidal neurons (PNs) have both transcriptional and structural alterations that suggest they are hypoactive. PN hypoactivity is thought to produce synaptic alterations in schizophrenia, however the effects of lower neuronal activity on synaptic function in primate DLPFC have not been examined. Here, we used, for the first time in primate neocortex, adeno-associated viral vectors (AAVs) to reduce PN excitability with Kir2.1 channel overexpression and tested if this manipulation altered the strength of synaptic inputs onto the Kir2.1-overexpressing PNs. Recordings in DLPFC slices showed that Kir2.1 overexpression depressed excitatory (but not inhibitory), synaptic currents, suggesting that, in schizophrenia, the hypoactivity of PNs might be exacerbated by reduced strength of the excitatory synapses they receive.
PubMed: 38915638
DOI: 10.1101/2024.06.12.598658 -
BioRxiv : the Preprint Server For... Jun 2024The basic excitatory neurons of the cerebral cortex, the pyramidal cells, are the most important signal integrators for the local circuit. They have quite characteristic...
The basic excitatory neurons of the cerebral cortex, the pyramidal cells, are the most important signal integrators for the local circuit. They have quite characteristic morphological and electrophysiological properties that are known to be largely constant with age in the young and adult cortex. However, the brain undergoes several dynamic changes throughout life, such as in the phases of early development and cognitive decline in the aging brain. We set out to search for intrinsic cellular changes in supragranular pyramidal cells across a broad age range: from birth to 85 years of age and we found differences in several biophysical properties between defined age groups. During the first year of life, subthreshold and suprathreshold electrophysiological properties changed in a way that shows that pyramidal cells become less excitable with maturation, but also become temporarily more precise. According to our findings, the morphological features of the three-dimensional reconstructions from different life stages showed consistent morphological properties and systematic dendritic spine analysis of an infantile and an old pyramidal cell showed clear significant differences in the distribution of spine shapes. Overall, the changes that occur during development and aging may have lasting effects on the properties of pyramidal cells in the cerebral cortex. Understanding these changes is important to unravel the complex mechanisms underlying brain development, cognition and age-related neurodegenerative diseases.
PubMed: 38915496
DOI: 10.1101/2024.06.13.598792 -
Frontiers in Cellular Neuroscience 2024Insulin-like growth factor-I (IGF-I) plays a key role in the modulation of synaptic plasticity and is an essential factor in learning and memory processes. However,...
Insulin-like growth factor-I (IGF-I) plays a key role in the modulation of synaptic plasticity and is an essential factor in learning and memory processes. However, during aging, IGF-I levels are decreased, and the effect of this decrease in the induction of synaptic plasticity remains unknown. Here we show that the induction of N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) at layer 2/3 pyramidal neurons (PNs) of the mouse barrel cortex is favored or prevented by IGF-I (10 nM) or IGF-I (7 nM), respectively, when IGF-I is applied 1 h before the induction of Hebbian LTP. Analyzing the cellular basis of this bidirectional control of synaptic plasticity, we observed that while 10 nM IGF-I generates LTP (LTP) of the post-synaptic potentials (PSPs) by inducing long-term depression (LTD) of the inhibitory post-synaptic currents (IPSCs), 7 nM IGF-I generates LTD of the PSPs (LTD) by inducing LTD of the excitatory post-synaptic currents (EPSCs). This bidirectional effect of IGF-I is supported by the observation of IGF-IR immunoreactivity at both excitatory and inhibitory synapses. Therefore, IGF-I controls the induction of Hebbian NMDAR-dependent plasticity depending on its concentration, revealing novel cellular mechanisms of IGF-I on synaptic plasticity and in the learning and memory machinery of the brain.
PubMed: 38910964
DOI: 10.3389/fncel.2024.1390663 -
Scientific Reports Jun 2024Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to...
Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to emulate the visual experience of movement during head fixation, but a low inertia floating real-world environment (mobile homecage, MHC) has the potential to engage more sensory modalities and provide a richer experimental environment for complex behavioral tasks. However, it is not known whether mice react to this adapted environment in a similar manner to real environments, or whether the MHC can be used to implement validated, maze-based behavioral tasks. Here, we show that hippocampal place cell representations are intact in the MHC and that the system allows relatively long (20 min) whole-cell patch clamp recordings from dorsal CA1 pyramidal neurons, revealing sub-threshold membrane potential dynamics. Furthermore, mice learn the location of a liquid reward within an adapted T-maze guided by 2-dimensional spatial navigation cues and relearn the location when spatial contingencies are reversed. Bilateral infusions of scopolamine show that this learning is hippocampus-dependent and requires intact cholinergic signalling. Therefore, we characterize the MHC system as an experimental tool to study sub-threshold membrane potential dynamics that underpin complex navigation behaviors.
Topics: Animals; Mice; Spatial Navigation; Maze Learning; Male; Hippocampus; Pyramidal Cells; Mice, Inbred C57BL; Membrane Potentials; CA1 Region, Hippocampal; Virtual Reality; Scopolamine; Patch-Clamp Techniques
PubMed: 38906952
DOI: 10.1038/s41598-024-64807-w -
Cell Reports Jun 2024Perceptual success depends on fast-spiking, parvalbumin-positive interneurons (FS/PVs). However, competing theories of optimal rate and correlation in pyramidal (PYR)...
Perceptual success depends on fast-spiking, parvalbumin-positive interneurons (FS/PVs). However, competing theories of optimal rate and correlation in pyramidal (PYR) firing make opposing predictions regarding the underlying FS/PV dynamics. We addressed this with population calcium imaging of FS/PVs and putative PYR neurons during threshold detection. In primary somatosensory and visual neocortex, a distinct PYR subset shows increased rate and spike-count correlations on detected trials ("hits"), while most show no rate change and decreased correlations. A larger fraction of FS/PVs predicts hits with either rate increases or decreases. Using computational modeling, we found that inhibitory imbalance, created by excitatory "feedback" and interactions between FS/PV pools, can account for the data. Rate-decreasing FS/PVs increase rate and correlation in a PYR subset, while rate-increasing FS/PVs reduce correlations and offset enhanced excitation in PYR neurons. These findings indicate that selection of informative PYR ensembles, through transient inhibitory imbalance, is a common motif of optimal neocortical processing.
PubMed: 38905102
DOI: 10.1016/j.celrep.2024.114233 -
Frontiers in Psychiatry 2024Social isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate...
BACKGROUND
Social isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate and developmental effects of social isolation on firing properties, neuronal activity-regulated pentraxin (NARP) and parvalbumin (PV) expression in the prefrontal cortex (PFC), social behavior in juvenile socially isolated mice, and the biological relevance of NARP expression in autism spectrum disorder (ASD).
METHODS
Mice were subjected to social isolation during postnatal days 21-35 (P21-P35) and were compared with group-housed control mice. Firing properties in the PFC pyramidal neurons were altered in P35 socially isolated mice, which might be associated with alterations in NARP and PV expression.
RESULTS
In adulthood, mice that underwent juvenile social isolation exhibited difficulty distinguishing between novel and familiar mice during a social memory task, while maintaining similar levels of social interaction as the control mice. Furthermore, a marked decrease in NARP expression in lymphoblastoid cell lines derived from adolescent humans with ASD as compared to typically developing (TD) humans was found.
CONCLUSION
Our study highlights the role of electrophysiological properties, as well as NARP and PV expression in the PFC in mediating the developmental consequences of social isolation on behavior.
PubMed: 38903649
DOI: 10.3389/fpsyt.2024.1403476