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Graziano, M.

Publications and source records attributed to Graziano, M..

8 recordsLinked to original sources

From microbiome to sperm motility traits: An inside out perspective

Growing interest in the relationship between microbiome composition and host biology has revealed the many ways host-associated microbes influence physiology, ecology, and evolution. However, microbial communities associated with reproductive organs - and their roles in reproduction - remain poorly understood. Here, we characterized the skin- and ejaculate-associated microbiomes in an internally fertilizing fish and tested whether microbial diversity and specific bacterial taxa correlate with sperm motility traits key for reproductive success. We used the guppy (Poecilia reticulata), a well-established model in ecology and evolutionary biology with well-characterised reproductive physiology. In guppies, sperm velocity is a validated predictor of male reproductive performance, making them a powerful system for exploring microbiome-fertility interactions. Our analyses reveal a correlation between skin microbiome diversity and sperm performance. Notably, increased skin microbiome total richness is associated with reduced sperm velocity, whereas no significant associations were detected for ejaculate-associated microbiomes. We also identified bacterial taxa across both tissues that were positively or negatively linked with sperm performance. These findings suggest that, while the ejaculate-associated microbiome may directly influence sperm traits, the skin microbiome could serve as a proxy for reproductive potential by reflecting systemic physiological and immunological states associated with fertility.

microbiology↗

A molecular atlas of cell-type specific signatures in the parkinsonian striatum.

The progressive degeneration of dopaminergic projections to the striatum is a key disease mechanism in Parkinsons disease (PD). To define the cellular landscape in the parkinsonian striatum, we mapped the cell-type specific transcriptional landscape in early and progressive PD mouse models and in human PD stages. Our analyses revealed substantial transcriptomic changes across both neuronal and glial populations, with astrocytes and oligodendrocytes exhibiting distinct disease-associated gene expression profiles. Notably, progressive dopamine depletion uncovered differential neuronal vulnerability, identifying eccentric striatal projection neurons (SPNs) and Chst9-expressing direct-pathway SPNs as among the most resilient subtypes in both species. This cross-species resource establishes a comprehensive framework for investigating cell-state dynamics in the parkinsonian striatum and uncovers selectively vulnerable and resistant cell types that can inspire new therapeutic strategies.

neuroscience↗

A striosomal accumbens pathway drives compulsive seeking behaviors through an aversive Esr1+ hypothalamic-habenula circuit.

The lateral hypothalamic area (LHA) integrates external stimuli with internal states to drive the choice between competing innate or value-driven motivated behaviors. Projections from the LHA to the lateral habenula (LHb) shape internal states, with excitatory estrogen receptor 1-expressing (Esr1+) LHA-LHb neurons driving aversive responses and sustained negative states. Here, we identify and functionally characterize a specific projection from the nucleus accumbens (ACB) that targets Esr1+ LHA-LHb neurons. Using cell-type-specific tracing of monosynaptic inputs, single-nucleus RNA sequencing, and neuroanatomical mapping, we demonstrate that the Esr1+ LHA-LHb pathway receives a major input from a striosomal Tac1+/Tshz1+/Oprm1+ ACB neuron subtype. Intersectional cell-type-specific and input-output defined optogenetic manipulation of this ACB-LHA-LHb pathway revealed its role in signaling aversion after repeated activation, with the negative behavioral state being dependent on recruitment of Esr1+ LHA-LHb neurons. Importantly, we found that activation of the D1+ ACB-LHA pathway drives reward-independent compulsive-like seeking behaviors, expressed as compulsive digging or poking behaviors. We found that these complex yet stereotyped behaviors compete with highly motivated states and can override the need for natural rewards or social stimuli. Our findings reveal a discrete striosomal Tac1+ ACB projection targeting the aversive Esr1+ LHA-LHb pathway as a key circuit that promotes compulsive seeking behaviors over goal-directed actions.

neuroscience↗

Meta-awareness, mind-wandering, and the control of 'default' external and internal orientations of attention

The "default mode" of cognition refers to the tendency to simulate internal experiences, rather than attending to external events in the moment. But in some contexts, external focus can become captivating enough to act as the default mode. To explore the relationship between prepotent internal and external default modes, we measured brain activity in forty participants using fMRI. Naturalistic movie clips were viewed, each one four times in sequence. When subjects were asked to focus attention on the videos, more mind-wandering events (distractions from the externally-focused task) occurred as the videos became less interesting with each repetition, and also when less engaging videos were presented. When subjects were asked to focus internally on breathing, more mind-wandering events (distractions from the internally-focused task) occurred when videos were most interesting (on the first repetition) and when more engaging videos were presented. In the fMRI data, inter-subject correlation, within-subject correlation, and GLM analyses found similar fronto-parietal networks engaged in transitions between default-controlled states regardless of the internal-external distinction, indicating more overlap in internal-external processing than previously assumed. We suggest that whether the default state is internal or external, and whether the sources that disrupt it are internal or external, depend on context.

neuroscience↗

Ecotype-specific genomic features within the Escherichia cryptic clade IV

Escherichia cryptic clades represent a relatively unexplored taxonomic cluster believed to exhibit characteristics associated with a free-living lifestyle, which is known as the environmental hypothesis. This hypothesis suggests that certain Escherichia strains harbour traits that favour their environmental persistence, thus expanding the ecological commensal niche of the genus. While surveying Escherichia diversity in an urban South American stream we isolated the first environmental cryptic clade IV strain in South America (339_SF). Here we report the genomic characterization of 339_SF strain in the context of existing genomic information for cryptic clade IV. A comparative analysis of genomes within the same clade stemming from diverse ecological sources and geographical locations reveals close phylogenetic proximity between our isolate and strains of environmental origin. In the genomes of cryptic clade IV strains that were isolated from environmental niches we observed enrichment of functional genes related to responses to adverse environmental conditions and a low number of genes with clinical relevance among. Our findings highlight substantial intra-group genomic structuring linked to ecological origin and shed light on the genomic mechanisms underlying the naturalization phenomena within the Escherichia genus.

microbiology↗

Esr1+ hypothalamic-habenula neurons shape aversive states.

Excitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) drive aversive responses. We used Patch-seq guided multimodal classification to define the structural and functional heterogeneity of the LHA-LHb pathway. Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles, and projection patterns. We found that genetically-defined LHA-LHb neurons signal distinct aspects of emotional or naturalistic behaviors: Esr1+ LHA-LHb neurons induce aversion, whereas Npy+ LHA-LHb neurons control rearing behavior. Repeated optogenetic drive of Esr1+ LHA-LHb neurons induces a behaviorally persistent aversive state, and large-scale recordings showed a region-specific neural representation of the aversive state in the prelimbic region of the prefrontal cortex. We further found that exposure to unpredictable mild shocks induced a sex-specific sensitivity to develop a stress state in female mice, which was associated with a specific shift in the intrinsic properties of bursting-type Esr1+ LHA-LHb neurons. In summary, we describe the diversity of LHA-LHb neuron types, and provide evidence for the role of Esr1+ neurons in aversion and sexually dimorphic stress sensitivity.

neuroscience↗

Frequency-dependent viscosity of salmon ovarian fluid has biophysical implications for sperm-egg interactions

Gamete-level sexual selection of externally fertilising species is usually achieved by modifying sperm behaviour with mechanisms thought to alter the chemical environment in which gametes perform. In fish this can be accomplished through the ovarian fluid, a substance released with the eggs at spawning. While its biochemical effects in relation to sperm energetics have been investigated, the influence of the physical environment in which sperm compete remains poorly explored. Our objective was therefore to gain insights on the physical structure of this fluid and potential impacts on reproduction. Using soft-matter physics approaches of steady-state and oscillatory viscosity measurements, we subjected salmon ovarian fluids to variable shear stresses and frequencies resembling those exerted by sperm swimming through the fluid near eggs. We show that this fluid, which in its relaxed state is a gel-like substance, displays a non-Newtonian viscoelastic and shear-thinning profile, where the viscosity decreases with increasing shear rates. We concurrently find that this fluid obeys the Cox-Merz rule below 7.6 Hz and infringes it above, thus indicating a shear-thickening phase where viscosity increases provided it is probed gently enough. This suggests the presence of a unique frequency-dependant structural network with relevant implications on sperm energetics and fertilisation dynamics.

evolutionary biology↗

Temporo-Parietal Cortex Involved in Modeling One's Own and Others' Attention

In a traditional view, in social cognition, attention is equated with gaze and people track attention by tracking other peoples gaze. Here we used fMRI to test whether the brain represents attention in a richer manner. People read stories describing an agent (either oneself or someone else) directing attention to an object in one of two ways: either internally directed (endogenous) or externally induced (exogenous). We used multivoxel pattern analysis to examine how brain areas within the theory-of-mind network encoded attention type and agent type. Brain activity patterns in the left temporo-parietal junction (TPJ) showed significant decoding of information about endogenous versus exogenous attention. The left TPJ, left superior temporal sulcus (STS), precuneus, and medial prefrontal cortex (MPFC) significantly decoded agent type (self versus other). These findings show that the brain constructs a rich model of ones own and others attentional state, possibly aiding theory of mind. Impact statementThis study used fMRI to show that the human brain encodes other peoples attention in enough richness to distinguish whether that attention was directed exogenously (stimulus-driven) or endogenously (internally driven).

neuroscience↗