Biology subjects

De Falco, E.

Publications and source records attributed to De Falco, E..

9 recordsLinked to original sources

bioRxiv2023

Changes in spatial self-consciousness elicit grid cell-like representation in entorhinal cortex

Grid cells in entorhinal cortex (EC) encode an individuals location in space and rely on environmental cues and multisensory bodily cues. Body-derived signals are also primary signals for the sense of self as the continuous application of visuo-tactile bodily stimuli elicits illusory drifts in perceived self-location. It is unknown whether illusory changes in self-location are sufficient to elicit grid cell like representation (GCLR) in EC and how this compares to GCLR during conventional virtual navigation. Our results show that illusory changes in perceived self-location (independent of changes in environmental navigation cues and explicit imagined navigation) evoke entorhinal GCLR, correlating in strength with the magnitude of perceived self-location, and characterized by similar grid orientation as during conventional virtual navigation. These data demonstrate that the same grid-like representation is recruited when navigating based on environmental, mainly visual cues, or when experiencing illusory forward drifts in self-location, driven by perceptual multisensory bodily cues.

neuroscience↗

bioRxiv2023

Flexible coding schemes in dorsomedial prefrontal cortex underlie decision-making during delay discounting

Determining how an agent decides between a small, immediate versus a larger, delayed reward has provided insight into the psychological and neural basis of decision-making. The tendency to excessively discount the value of delayed rewards is thought to reflect deficits in brain regions critical for impulse control such as the prefrontal cortex (PFC). This study tested the hypothesis that dorsomedial PFC (dmPFC) is critically involved in flexibly managing neural representations of strategies that limit impulsive choices. Optogenetic silencing of neurons in the rat dmPFC increased impulsive choices at an 8 sec, but not 4 sec, delay. Neural recordings from dmPFC ensembles revealed that, at the 8-sec delay, the encoding landscape transitions to reflect a deliberative-like process rather than the schema-like processes observed at the 4-sec delay. These findings show that changes in the encoding landscape reflect changes in task demands and that dmPFC is uniquely involved in decisions requiring deliberation.

neuroscience↗

bioRxiv2023

Real-world body orientation impacts virtual navigation experience and performance

Most human navigation studies in MRI rely on virtual navigation. However, the necessary supine position in MRI makes it fundamentally different from daily ecological navigation. Nonetheless, until now, no study has assessed whether differences in physical body orientation (BO) affect participants experienced BO during virtual navigation. Here, combining an immersive virtual reality (VR) navigation task with subjective BO measures and implicit behavioral measures, we demonstrate that physical BO (either standing or supine) modulated experienced BO. Also, we show that standing upright BO is preferred during spatial navigation: participants were more likely to experience a standing BO and were better at spatial navigation when standing upright. Importantly, we report that showing a supine virtual agent reduces the conflict between the preferred BO and physical supine BO. Our study provides critical, but missing, information regarding experienced BO during virtual navigation, which should be considered cautiously when designing navigation studies, especially in MRI. Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/527966v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@7a4df0org.highwire.dtl.DTLVardef@192f0d7org.highwire.dtl.DTLVardef@1ba37org.highwire.dtl.DTLVardef@168866c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Investigating the risk of cardiac fibrosis due to heat-not-burn cigarettes through human cardiac stromal cells

BackgroundThe use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain. ObjectiveTo investigate the effects of circulating molecules in HNBC chronic smokers on the fibrotic specification and paracrine function of cardiac stromal cells (CSCs). MethodsResident CSCs were isolated from the atrial tissue of patients with cardiovascular diseases, and exposed to the serum of 60 young healthy subjects, stratified in exclusive HNBC smokers, traditional combustion cigarette (TCC) smokers, or non-smokers (NS) as reference. ResultsCSCs treated with TCC serum displayed impaired 3D growth and migration, as well as increased expression and/or release of pro-inflammatory and pro-fibrotic cytokines. Cells cultured with HNBC serum showed increased mRNA levels of pro-fibrotic genes, and reduced expression of the gap junction protein CX43. Nonetheless, both TCC and HNBC sera reduced the release of angiogenic and protective factors from CSCs. In fact, their paracrine support to tube-formation by endothelial cells and to preserved cell viability of cardiomyocytes in culture was significantly impaired. Treatment with the sera of both types of smokers also increased the expression of NOX isoforms and the release of H2O2 by CSCs. ConclusionThe circulating molecules in the serum of chronic HNBC smokers induce fibrotic specification in CSCs. They also reduce the beneficial paracrine effects of stromal cells on endothelial cells and cardiomyocytes, albeit to a reduced extent for some features. These results point to a potential risk for atrial fibrosis development triggered by chronic HNBC use. CONDENSED ABSTRACTThe use of alternative smoking devices, such as heat-not-burn cigarettes (HNBC), is increasing on a global scale, and their impact on health is still uncertain. We isolated human stromal cells from the atrial tissue of patients with cardiovascular diseases, and exposed them to the serum of young healthy subjects, that are exclusive HNBC smokers. Results showed significant alterations in the phenotype of CSCs exposed to HNBC serum, suggesting a specification towards fibrosis, reduced support to parenchymal cells, and increased oxidative stress production. Data point to a potential risk for atrial fibrosis development triggered by chronic HNBC use.

pathology↗

bioRxiv2022

Single neurons in thalamus and subthalamic nucleus process cardiac and respiratory signals in humans

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: Ventral Intermedius nucleus (Vim) and Ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. We observed neurons with increases or decreases in firing rate in response to either the heartbeat or the inter-beat interval. Peaks of neural activity were found at different phases of the cardiac and respiratory cycles. Whereas most neurons only responded to one of the tested signals, a substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing for the first time single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.

neuroscience↗

bioRxiv2022

Remote adipose tissue-derived stromal cells of patients with lung adenocarcinoma generate a similar malignant microenvironment of the lung stromal counterpart

Cancer alters both local and distant tissue by influencing the microenvironment. In this regard, the interplay with the stromal fraction is considered critical as this latter can either foster or hamper the progression of the disease. Accordingly, the modality by which tumor may alter distant niches of stromal cells is still unclear, expecially at early stages. In this short report we attempt to better understand the biology of this cross talk. In our "autologous stromal experimental setting", we found that remote adipose tissue-derived mesenchymal stem cells (mediastinal AMSC) obtained from patients with lung adenocarcinoma sustain proliferation and clonogenic ability of A549 and human primary lung adenocarcinoma cells similarly to the autologous stromal lung counterpart (LMSC). This effect is not observed in lung benign diseases as the hamartochondroma. This finding was validated by conditioning benign AMSC with supernatants from LAC up to 21 days. The new reconditioned media of the stromal fraction so obtained, was able to increase cell proliferation of A549 cells at 14 and 21 days similarly to that derived from AMSC of patients with lung adenocarcinoma. The secretome generated by remote AMSC revealed overlapping to the corresponding malignant microenvironment of the autologous local LMSC. Among the plethora of 80 soluble factors analysed by arrays, a small pool of 5 upregulated molecules including IL1-{beta}, IL-3, MCP-1, TNF- and EGF, was commonly shared by both malignant-like autologous A- and LMSC derived microenvironments vs those benign. The bioinformatic analysis both revealed that these proteins were strictly and functionally interconnected to the lung fibrosis and proinflammation and that miR-126, 101, 486 and let-7-g were their main targets. Accordingly, we found that in lung cancer tissues and blood samples from the same set of patients here employed, miR-126 and miR-486 displayed the highest expression levels in tissue and blood, respectively.

cell biology↗

bioRxiv2022

Human platelet lysate derived extracellular vesicles enhance angiogenesis through miR-126

Objectivesextracellular vesicles (EVs) are key biological mediators of several physiological functions within the cell microenvironment. Platelets are the most abundant source of EVs in the blood. Similarly, platelet lysate (PL), the best platelet derivative and angiogenic performer for regenerative purposes, is enriched of EVs, but their role is still too poorly discovered to be suitably exploited. Here we explored the contribution of the EVs in PL, by investigating the angiogenic features extrapolated from that possessed by PL. Methodswe tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL-derived EVs. Resultsa subset of small vesicles is highly represented in PL. The EVs do not retain aggregation ability, preserving a low redox state in HUVEC and increasing the angiogenic tubularly-like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched of small RNAs and a high amount of miR-126, the most abundant angiogenic miRNA in platelets. The transfer of miR-126 by EVs in HUVEC after the in vitro inhibition of the endogenous form, restored angiogenesis, without involving VEGF as downstream target in this system. ConclusionsPL is a biological source of available EVs with angiogenic effects involving a miRNAs-based cargo. These properties can be exploited for targeted molecular/biological manipulation of PL, by potentially developing a product exclusively manufactured of EVs.

cell biology↗

bioRxiv2021

When shared concept cells support associations: theory of overlapping memory engrams

Assemblies of neurons, called concepts cells, encode acquired concepts in human Medial Temporal Lobe. Those concept cells that are shared between two assemblies have been hypothesized to encode associations between concepts. Here we test this hypothesis in a computational model of attractor neural networks. We find that for concepts encoded in sparse neural assemblies there is a minimal fraction cmin of neurons shared between assemblies below which associations cannot be reliably implemented; and a maximal fraction cmax of shared neurons above which single concepts can no longer be retrieved. In the presence of a periodically modulated background signal, such as hippocampal oscillations, recall takes the form of association chains reminiscent of those postulated by theories of free recall of words. Predictions of an iterative overlap-generating model match experimental data on the number of concepts to which a neuron responds. Authors contributionsAll authors contributed to conception of the study and writing of the manuscript. CG and TS developed the theory. CG wrote the code for all figures. EDF and RQQ provided the experimental data. EDF and CG analyzed the data. WG and CG developed algorithms to fit the experimental data.

neuroscience↗

bioRxiv2018

The rat medial prefrontal cortex exhibits flexible neural activity states during the performance of an odor span task

Medial prefrontal cortex (mPFC) activity is fundamental for working memory (WM), attention, and behavioral inhibition; however, a comprehensive understanding of the neural computations underlying these processes is still forthcoming. Towards this goal, neural recordings were obtained from the mPFC of awake, behaving rats performing an odor span task of WM capacity. Neural populations were observed to encode distinct task epochs and the transitions between epochs were accompanied by abrupt shifts in neural activity patterns. Putative pyramidal neuron activity increased significantly earlier in the delay for sessions where rats achieved higher spans. Furthermore, increased putative interneuron activity was only observed at the termination of the delay thus indicating that local processing in inhibitory networks was a unique feature to initiate foraging. During foraging, changes in neural activity patterns associated with the approach to a novel odor, but not familiar odors, were robust. Collectively, these data suggest that distinct mPFC activity states underlie the delay, foraging, and reward epochs of the odor span task. Transitions between these states enable successful performance in dynamic environments placing strong demands on the substrates of working memory.

neuroscience↗