Project description:Somatostatin (SST)-expressing inhibitory neurons are a major class of neocortical γ-amino butyric acid (GABA) neurons, where morphological, electrophysiological, and transcriptomic analyses indicate more than a dozen different subtypes. However, whether this diversity is related to specific roles in cortical computations and plasticity remains unclear. Here we identify learning-dependent, subtype-specific plasticity in layer 2/3 SST neurons of the mouse somatosensory cortex. Martinotti-type, SST neurons expressing calbindin-2 show a selective decrease in excitatory synaptic input and stimulus-evoked calcium responses as mice learn a stimulus-reward association. Using these insights, we develop a label-free classifier using basal activity from in vivo imaging that accurately predicts learning-associated response plasticity. Our data indicate that molecularly-defined SST neuron subtypes play specific and highly-regulated roles in sensory information processing and learning.
Project description:During development, early regionalization segregates lineages and directs diverse cell fates. Sometimes, however, distinct progenitors produce analogous cell types. For example, V2a neurons, are excitatory interneurons that emerge from different anteroposterior progenitors. V2a neurons demonstrate remarkable plasticity after spinal cord injury and improve motor function, showing potential for cell therapy. To examine how lineage origins shape their properties, we differentiated V2a neurons from hPSC-derived progenitors with distinct anteroposterior identities. Single-nucleus multiomic analysis revealed lineage-specific transcription factor motifs and numerous differentially expressed genes related to axon growth and calcium handling. Bypassing lineage patterning via transcription factor-induced differentiation yielded neurons distinct from both developmentally relevant populations and human tissue, emphasizing the need to follow developmental steps to generate authentic cell identities. Using in silico and in vitro loss-of-function analyses, we identified CREB5 and TCF7L2 as regulators specific to posterior identities, underscoring the critical role of lieage origins in determining cell states and functions.
Project description:Regeneration of neuronal circuits cannot be successful without restoration of full function, including recovery of behavioral plasticity, which we have found is delayed after regeneration of specific synapses. Experiments were designed to measure neuronal changes that may underlie recovery of function. Sensitization of the leech withdrawal reflex is a non-associative form of learning that depends on the S-interneuron. Cutting an S-cell axon in Faivre's nerve disrupted the capacity for sensitization. The S-cell axon regenerated its electrical synapse with its homologous cell after 3-4 weeks, but the capacity for sensitization was delayed for an additional 2-3 weeks. In the present experiments another form of non-associative conditioning, dishabituation, was also eliminated by S-cell axotomy; it returned following regeneration. Semi-intact preparations were made for behavioral studies, and chains of ganglia with some skin were used for intracellular recording and skin stimulation. In both preparations there was a similar time-course, during 6 weeks, of a lesion-induced decrease and delayed restoration of both S-cell action potential threshold to depolarizing pulses and S-cell firing in response to test stimuli. However, the ability of sensitizing stimuli to decrease S-cell threshold and enhance S-cell activity in response to test stimuli did not fully return after regeneration, indicating that there were lasting changes in the circuit extending beyond the period necessary for full recovery of behavior. Intracellular recordings from the axotomized S-cell revealed a shift in the usual balance of excitatory and inhibitory input, with inhibition enhanced. These results indicate that loss of behavioral plasticity of reflexive shortening following axotomy in the S-cell chain may be related to reduced S-cell activity, and that additional processes underlie full recovery of sensitization of the whole body shortening reflex.
Project description:We develop a new model that explains how the cerebellum may generate the timing in classical delay eyeblink conditioning. Recent studies show that both Purkinje cells (PCs) and inhibitory interneurons (INs) have parallel signal processing streams with two time scales: an AMPA receptor-mediated fast process and a metabotropic glutamate receptor (mGluR)-mediated slow process. Moreover, one consistent finding is an increased excitability of PC dendrites (in Larsell's lobule HVI) in animals when they acquire the classical delay eyeblink conditioning naturally, in contrast to in vitro studies, where learning involves long-term depression (LTD). Our model proposes that the delayed response comes from the slow dynamics of mGluR-mediated IP3 activation, and the ensuing calcium concentration change, and not from LTP/LTD. The conditioned stimulus (tone), arriving on the parallel fibers, triggers this slow activation in INs and PC spines. These excitatory (from PC spines) and inhibitory (from INs) signals then interact at the PC dendrites to generate variable waveforms of PC activation. When the unconditioned stimulus (puff), arriving on the climbing fibers, is coupled frequently with this slow activation the waveform is amplified (due to an increased excitability) and leads to a timed pause in the PC population. The disinhibition of deep cerebellar nuclei by this timed pause causes the delayed conditioned response. This suggested PC-IN interaction emphasizes a richer role of the INs in learning and also conforms to the recent evidence that mGluR in the cerebellar cortex may participate in slow motor execution. We show that the suggested mechanism can endow the cerebellar cortex with the versatility to learn almost any temporal pattern, in addition to those that arise in classical conditioning.
Project description:Adhesive restorations have been shown to guarantee excellent performance and longevity, although this comes with some disadvantages. Among these, the vulnerability of dentine to different agents has been widely evaluated. The aim of this study was to evaluate the possible penetration of impression materials into freshly cut dentine. Dentine from 27 teeth was impressed with polyether (Impregum Penta L) (nine teeth) and with polyvinyl siloxane (Aquasil Ultra LV) (nine teeth). The surface of nine teeth after the impressions were used as the control. Specifically, the extroflections caused by the imprinting of the dentinal tubules on the impression material, the so-called impression tags, were measured. Furthermore, the presence of the material inside the tubules was examined. Scanning electron microscopy analysis showed material tags for all of the experimental groups. The mean lengths (±SD) were 22.6 (±11.0) µm for polyether, 21.8 (±12.8) µm for polyvinyl siloxane and 11.3 (±7.0) µm for the tooth control, with mean diameters (±SD) of 2.8 (±0.5), 2.4 (±0.7) and 3.1 (±0.7) µm, respectively. Fractal analysis showed fractal dimensions of 1.78 (±0.03), 1.77 (±0.03) and 1.71 (±0.03), respectively. These data demonstrated that the impression materials can remain inside the dentinal tubules, which can adversely affect the adhesive procedures.
Project description:BackgroundAntibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing.ResultsWhile the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate.ConclusionsWe demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition. Video abstract.
Project description:Previous neuroimaging studies demonstrated that ventromedial prefrontal cortex (vmPFC) activity reflects how much an individual positively views each person (impression). Here, we investigated whether the degree to which individuals think others positively view them (reflected impression) is similarly tracked by activity in the vmPFC by using fMRI and speed-dating events. We also examined whether activity of the vmPFC in response to the faces of others would predict the impression formed through direct interactions with them. The task consisted of three sessions: pre-speed-dating fMRI, speed-dating events, and post-speed-dating fMRI (not reported here). During the pre-speed-dating fMRI, each participant passively viewed the faces of others whom they would meet in the subsequent speed-dating events. After the fMRI, they rated the impression and reflected impression of each face. During the speed-dating events, the participants had 3-min conversations with partners whose faces were presented during the fMRI task, and they were asked to choose the partners whom they preferred at the end of the events. The results revealed that the value of both the impression and reflected impression were automatically represented in the vmPFC. However, the impression fully mediated the link between the reflected impression and vmPFC activity. These results highlight a close link between reflected appraisal and impression formation and provide important insights into neural and psychological models of how the reflected impression is formed in the human brain.
Project description:The sense of smell arises from the perception of odors from chemicals. However, the relationship between the impression of odor and the numerous physicochemical parameters has yet to be understood owing to its complexity. As such, there is no established general method for predicting the impression of odor of a chemical only from its physicochemical properties. In this study, we designed a novel predictive model based on an artificial neural network with a deep structure for predicting odor impression utilizing the mass spectra of chemicals, and we conducted a series of computational analyses to evaluate its performance. Feature vectors extracted from the original high-dimensional space using two autoencoders equipped with both input and output layers in the model are used to build a mapping function from the feature space of mass spectra to the feature space of sensory data. The results of predictions obtained by the proposed new method have notable accuracy (R≅0.76) in comparison with a conventional method (R≅0.61).
Project description:BackgroundThis study aimed to compare the precision and trueness of digital impressions of the edentulous arch made with different scanners to conventional physical impressions.MethodsA total of 40 impressions of a completely edentulous maxillary arch model (n = 10) were made using different digital impressions with an extraoral scanner, E3 3Shape desktop scanner, as the reference scan, intraoral scanner (TRIOS IOS, and Medit IOS) and Vinyl Polysiloxane impressions (VPS) impression using a Computer-Aided Design and Computer-Aided Manufacturing (CAD-CAM) custom tray. The VPS impression was scanned with the desktop scanner to produce standard tessellation language (STL) files for comparison with the digital impressions made by the Desktop and intraoral scanners. The STL files were super-imposed to a desktop scan and to each other with the same group using Geomagic Control X Software to assess the trueness and precision, respectively. A t-test was conducted for statistical analysis with a significance level of 0.05.ResultsThe overall trueness, Medit had the highest deviation compared to the VPS and TRIOS groups with a P value of 0.0013 and <0.0001, respectively. In terms of overall precision, TRIOS had a lower deviation than the VPS group, with a P value of 0.0002. The TRIOS and Medit groups had statistically comparable results. The desktop scanner showed the highest precision in digitizing completely edentulous cases, followed by the TRIOS scanner. The Medit scanner's trueness had the highest deviation compared to the VPS and TRIOS groups.
Project description:Prior work has shown that whether or not someone is similar to the self influences person memory--a type of self-reference effect for others. In this study, we were interested in understanding the neural regions supporting the generation of impressions and subsequent memory for targets who vary in similarity to the self. Participants underwent fMRI scanning while forming positive or negative impressions of face-behavior pairs. We tested participants' memory for their generated impressions and then back-sorted the impression trials (encoding) into different levels of self-similarity (high, medium, low) using a self-similarity posttest that came after recognition. Extending prior behavioral work, our data confirmed our hypothesis that memory would be highest for self-similar others and lowest for self-dissimilar others. Dorsal anterior cingulate cortex (dACC) activity increased with self-similarity (high > medium > low) to targets, regardless of later memory for them. An analysis of regions supporting impression memory revealed a double dissociation within medial temporal lobe regions: for similar others, amygdala recruitment supported memory, whereas for dissimilar others, hippocampal activation supported memory. These results suggest that self-similarity influences evaluation and memory for targets but also affects the underlying neural resources engaged when thinking about others who vary in self-similarity.