Biology subjects

Sarno, S.

Publications and source records attributed to Sarno, S..

12 recordsLinked to original sources

bioRxiv2024

Somatostatin interneurons select dorsomedial striatal representations of the initial learning phase

The dorsomedial striatum (DMS) is an associative node involved in the adaptation of ongoing actions to the environmental context and in the initial formation of motor sequences. In early associative or motor learning phases, DMS activity shows a global decrease in neuron firing, eventually giving rise to a select group of active cells, whose number is correlated with animal performance. Unveiling how those representation emerge from DMS circuits is crucial for understanding plasticity mechanisms of early adjustments to learning a task. Here, we hypothesized that inhibitory microcircuits formed by local interneurons are responsible for the genesis of early DMS representation and associated task performance. Despite the low density of somatostatin (SOM)-positive cells, we observed that selective manipulation of SOM cells disrupted reorganization of DMS activity and modulated initial phases of learning in two behavioral contexts. This effect was cell-specific as manipulation of parvalbumin-positive interneurons had no significant effect. Finally, we identified the high plasticity of SOM innervation in the DMS as a key modulator of the SPN excitability and firing activity. Hence, SOM interneurons set the pace of early learning by actively controlling the remapping of DMS network activity.

neuroscience↗

bioRxiv2023

Convergent evolution of complex adaptive traits enabled human life at high altitudes

Convergent adaptations represent paradigmatic examples of the capacity of natural selection to influence organisms biology. However, the possibility to investigate genetic determinants underpinning convergent complex adaptive traits has been offered only recently by methods for inferring polygenic adaptations from genomic data. Relying on this approach, we demonstrate how high-altitude Andean human groups experienced pervasive selective events at angiogenic pathways, which resemble those previously attested for Himalayan populations despite partial convergence at the single-gene level was observed. This provides unprecedented evidence for the drivers of convergent evolution of enhanced blood perfusion in populations exposed to hypobaric hypoxia for thousands of years.

evolutionary biology↗

bioRxiv2023

Archaic introgression contributed to shape the adaptive modulation of angiogenesis and nitric oxide induction in human high-altitude populations from the Himalayas

It is well established that several Homo Sapiens populations experienced admixture with extinct human species during their evolutionary history. Sometimes, such a gene flow could have played a role in modulating their capability to cope with a variety of selective pressures, thus resulting in archaic adaptive introgression events. A paradigmatic example of this evolutionary mechanism is offered by the EPAS1 gene, whose most frequent haplotype in Himalayan highlanders was proved to reduce their susceptibility to chronic mountain sickness and to be introduced in the gene pool of their ancestors by admixture with Denisovans. In this study, we aimed at further expanding the investigation of the impact of archaic introgression on more complex adaptive responses to hypobaric hypoxia evolved by populations of Tibetan/Sherpa ancestry, which have been plausibly mediated by soft selective sweeps and/or polygenic adaptations rather than by hard selective sweeps. For this purpose, we used a combination of composite-likelihood and gene network-based methods to detect adaptive loci in introgressed chromosomal segments from Tibetan whole genome sequence data and to shortlist those presenting Denisovan-like derived alleles that participate to the same functional pathways and are absent in populations of African ancestry, which are supposed to do not have experienced Denisovan admixture. According to this approach, we identified multiple genes putatively involved in archaic introgression events and that, especially as regards TBC1D1, RASGRF2, PRKAG2, and KRAS, have plausibly contributed to shape the adaptive modulation of angiogenesis and of certain cardiovascular traits in high-altitude Himalayan peoples. These findings provided unprecedented evidence about the complexity of the adaptive phenotype evolved by these human groups to cope with challenges imposed by hypobaric hypoxia, offering new insights into the tangled interplay of genetic determinants that mediates the physiological adjustments crucial for human adaptation to the high-altitude environment.

evolutionary biology↗

bioRxiv2021

Dietary, Cultural and Pathogens-related Selective Pressures Shaped Differential Adaptive Evolution Among Native Mexican Populations

Native American genetic ancestry has been remarkably implicated with increased risk of diverse health issues in several Mexican populations, especially in relation to the dramatic changes in environmental, dietary and cultural settings they have recently undergone. In particular, the effects of these ecological transitions and Westernization of lifestyles have been investigated so far predominantly on Admixed individuals. Nevertheless, indigenous groups, rather than admixed Mexicans, have plausibly retained the highest proportions of genetic components shaped by natural selection in response to the ancient milieu experienced by Mexican ancestors during their pre-Columbian evolutionary history. These formerly adaptive alleles/haplotypes have the potential to represent the genetic determinants of some biological traits peculiar to the Mexican people and a reservoir of loci with potential biomedical relevance. To test such a hypothesis, we used high-resolution genomic data to infer the unique adaptive evolution of 15 Native Mexican groups selected as reasonable descendants of the main pre-Columbian Mexican civilizations. A combination of haplotype-based and gene-network analyses enabled us to detect genomic signatures ascribable to polygenic adaptive traits evolved by the main genetic clusters of indigenous Mexican populations to cope with local environmental and/or cultural conditions. Some of them were also found to play a role in modulating the susceptibility/resistance of these groups to certain pathological conditions, thus providing new evidence for diverse selective pressures having contributed to shape current biological and disease-risk patterns in present-day Native and Mestizo Mexican populations.

evolutionary biology↗

bioRxiv2020

Midbrain dopamine firing activity codes reward expectation and motivation in a parametric working memory task

Little is known about how dopamine (DA) neuron firing rates behave in cognitively demanding decision-making tasks. Here we investigated midbrain DA activity in monkeys performing a discrimination task in which the animal had to use working memory (WM) to report which of two sequentially applied vibrotactile stimuli had the higher frequency. We found that perception was altered by an internal bias, likely generated by deterioration of the representation of the first frequency during the WM period. This bias greatly controlled the DA phasic response during the two stimulation periods, confirming that DA reward prediction errors reflected subjective stimulus perception. Contrastingly, tonic dopamine activity during WM was not affected by the bias and did not encode the stored frequency. More interestingly, both WM activity and phasic responses before the second stimulus negatively correlated with reaction times of the animal after the trial start cue and thus represented motivated behavior on a trial-by-trial basis. During WM, this motivation signal underwent a ramp-like increase. At the same time, motivation reduced noise in perception and, by decreasing the effect of the bias, improved performance, especially in difficult trials. Overall, our results show that DA activity was simultaneously involved in reward prediction, motivation and WM. Also, the ramping activity during the WM period suggests a possible DA role in stabilizing sustained cortical activity, hypothetically by increasing the gain communicated to prefrontal neurons in a motivation-dependent way.

neuroscience↗

bioRxiv2020

The dorsal striatum sets the sensitivity to effort

The dorsal striatum (dS) has been implicated in storing and retrieving procedural memories and controlling movement kinematics (e.g., speed). Since procedural memories are expressed through movements, the exact nature of the dS function has proven difficult to delineate. Here we challenged rats in complementary tasks designed to alleviate this performance confound. Surprisingly, dS lesions spared task-specific procedural memories but altered the kinematics of their expression in motor routines. Further behavioral analyses combined with simulations in the optimal control framework indicated that these alterations reflected an increased sensitivity to effort with preserved reward-seeking and ability to modulate movement speed. By setting the sensitivity to effort, the dS contributes to the optimization of the energy invested into voluntary movements. Such an elementary function of the dS might explain its implication in both procedural decisions and the control of movement speed.

neuroscience↗

bioRxiv2019

The Embodied Nature of Well-Timed Behavior

How animals adapt their movements to take advantage of behaviorally-relevant time intervals is not well understood, especially in the supra-second timescale. It has been proposed that motor timing depends on the emergence of self-sustained dynamics across ensembles of neurons. Alternatively, evidence from operant conditioning suggests that animals can develop motor routines to adapt their behavior to fixed temporal constraints. But it is unclear whether animals can accurately time their behavior without the help of motor routines. To address this issue, we used a task in which rats, freely moving on a motorized treadmill, could obtain a reward if they approached it after a fixed interval. Most animals took advantage of the treadmill length and its moving direction to develop, by trial-and-error, a unique motor routine whose execution resulted in the precise timing of their reward approaches. Noticeably, when proficient animals occasionally failed to follow this routine, the timing of their reward approaches was systematically poor. In a second step, we trained naive animals in modified versions of the task specifically designed to prevent the development of this motor strategy. Compared to rats trained in the first protocol, these animals never reached a comparable level of timing accuracy. We conclude that motor timing critically depends on the ability of animals to develop motor routines adapted to the structure of their environment. Our work also suggests that self-sustained neuronal activity alone may not be sufficient to support motor timing, at least in the supra-second timescale.

animal behavior and cognition↗

bioRxiv2019

The genomic impact of European colonization of the Americas

The human genetic diversity of the Americas has been shaped by several events of gene flow that have continued since the Colonial Era and the Atlantic slave trade. Moreover, multiple waves of migration followed by local admixture occurred in the last two centuries, the impact of which has been largely unexplored.\n\nHere we compiled a genome-wide dataset of [~]12,000 individuals from twelve American countries and [~]6,000 individuals from worldwide populations and applied haplotype-based methods to investigate how historical movements from outside the New World affected i) the genetic structure, ii) the admixture profile, iii) the demographic history and iv) sex-biased gene-flow dynamics, of the Americas.\n\nWe revealed a high degree of complexity underlying the genetic contribution of European and African populations in North and South America, from both geographic and temporal perspectives, identifying previously unreported sources related to Italy, the Middle East and to specific regions of Africa.

genomics↗

bioRxiv2019

Inter-individual genomic heterogeneity within European population isolates

A number of studies carried out since the early 70s has investigated the effects of isolation on genetic variation within and among human populations in diverse geographical contexts. However, no extensive analysis has been carried out on the heterogeneity among genomes within isolated populations. This issue is worth exploring since events of recent admixture and/or subdivision could potentially disrupt the genetic homogeneity which is to be expected when isolation is prolonged and constant over time. Here, we analyze literature data relative to 87,818 autosomal single-nucleotide polymorphisms, which were obtained from a total of 28 European populations. Our results challenge the traditional paradigm of population isolates as genetically (and genomically) uniform entities. In fact, focusing on the distribution of variance of intra-population diversity measures across individuals, we show that the inter-individual heterogeneity of isolated populations is at least comparable to the open ones. More in particular, three small and highly inbred isolates (Sappada, Sauris and Timau in Northeastern Italy) were found to be characterized by levels of this parameter largely exceeding that of all other populations, possibly due to relatively recent events of genetic introgression. Finally, we propose a way to monitor the effects of inter-individual heterogeneity in disease-gene association studies.

genomics↗

bioRxiv2018

Internal bias controls dopamine perceptual decision-related responses

Dopamine neurons produce reward-related signals that regulate learning and guide behavior. Prior expectations about forthcoming stimuli and internal biases can alter perception and choices and thus could influence dopamine signaling. We tested this hypothesis studying dopamine neurons recorded in monkeys trained to discriminate between two tactile frequencies separated by a delay period, a task affected by the contraction bias. The bias greatly controlled the animals choices and confidence on their decisions. During decision formation the phasic activity reflected bias-induced modulations and simultaneously coded reward prediction errors. In contrast, the activity during the delay period was not affected by the bias, was not tuned to the value of the stimuli but was temporally modulated, pointing to a role different from that of the phasic activity.

neuroscience↗

bioRxiv2017

Impact of non-LTR retrotransposons in the differentiation and evolution of Anatomically Modern Humans

Transposable Elements are biologically important components of eukaryote genomes. In particular, non-LTR retrotransposons (N-LTRrs) extensively shaped the human genome throughout evolution. In this study, we compared retrotransposon insertions differentially present in the genomes of Anatomically Modern Humans, Neanderthals, Denisovans and Chimpanzees, in order to assess the possible impact of retrotransposition in the differentiation of the human lineage. Briefly, we first identified species-specific N-LTRrs and established their distribution in present day human populations. These analyses shortlisted a group of N-LTRr insertions that were found exclusively in Anatomically Modern Humans. Notably, these insertions targeted genes more frequently than randomly expected and are associated with an increase in the number of transcriptional/splicing variants of those genes they inserted in. The analysis of the functionality of genes targeted by human-specific N-LTRr insertions seems to reflect phenotypic changes that occurred during human evolution. Furthermore, the expression of genes containing the most recent N-LTRr insertions is enriched in the brain, especially in undifferentiated neurons, and these genes associate in networks related to neuron maturation and migration. Additionally, we also identified candidate N-LTRr insertions that have likely produced new functional variants exclusive to modern humans, which show traces of positive selection and are now fixed in all present-day human populations. In sum, our results strongly suggest that N-LTRr impacted our differentiation as a species and have been a constant source of genomic variability all throughout the evolution of the human lineage.

genomics↗

bioRxiv2016

The Tell-Tale Genome

Observable patterns of cultural variation are consistently intertwined with demic movements, cultural diffusion, and adaptation to different ecological contexts (Cavalli-Sforza and Feldman 1981; Boyd and Richerson 1985). The quantitative study of gene-culture co-evolution has focused in particular on the mechanisms responsible for change in frequency and attributes of cultural traits, on the spread of cultural information through demic and cultural diffusion, and on detecting relationships between genetic and cultural lineages. Here, for the first time, we make use of worldwide whole-genome sequences (Pagani et al. 2016) to assess the impact of demic diffusion on cultural diversity, focusing on the variability observed in folktale traditions (N=596) (Uther 2004) in Eurasia and Africa. We show that at small geographic scales (<=5000 km) there is a strong correlation between folktale and genomic distance when the effect of geography is corrected, while geographic distance has no independent effect on the distribution of folkloric narratives at the same spatial scale. This points to demic processes (i.e. population movement and replacement) as the main driver of folktale transmission at limited geographic ranges. The role of population movements becomes more apparent when regions characterized by episodes of directional expansions, such as the Neolithization of West Eurasia, are examined. Furthermore, we identify 89 individual tales which are likely to be predominantly transmitted through demic diffusion, and locate putative focal areas for a subset of them.

evolutionary biology↗