Biology subjects

Alvino, F. G.

Publications and source records attributed to Alvino, F. G..

4 recordsLinked to original sources

bioRxiv2026

Cortical excitability inversely modulates fMRI connectivity via low-frequency neuronal coupling

The neural mechanisms supporting fMRI connectivity are poorly understood. Leveraging an aggregated analysis of novel and existing chemogenetic manipulations and electrophysiological recordings in the mouse medial prefrontal cortex (PFC), we show that local cortical excitability inversely modulates large-scale fMRI connectivity. Specifically, we find that bidirectional chemogenetic manipulations of cortical excitability produce opposite effects on fMRI connectivity, resulting in fMRI hypoconnectivity when excitability is enhanced, and fMRI hyperconnectivity when excitability is suppressed, despite corresponding increases or decreases in local neuronal firing. Notably, while each chemogenetic manipulation produces a distinct profile of interareal electrophysiological coherence, only low-frequency (< 4Hz) coherence predicts the direction and magnitude of the ensuing fMRI connectivity changes. Biophysical network modelling shows that the observed electrophysiological coherence profiles can arise from the interaction between direct inter-area communication changes mediated by local firing-rate variations, and shared larger-scale low-frequency covariation of ongoing neuronal activity. Together, our results reveal an inverse relationship between regional cortical excitability and large-scale fMRI connectivity, and indicate that fMRI connectivity is primarily supported by low frequency (<4 Hz) electrophysiological coupling. These findings open new avenues for modeling and interpreting fMRI connectivity in health, and in response to pathological or exogenous perturbations linked to cortical excitability.

neuroscience↗

bioRxiv2025

Functional specialization of the hippocampus along its dorso-ventral axis: from span to supraspan in working memory capacity

Working memory (WM) is characterized by a limited capacity or span, beyond which performance deteriorates, the supraspan condition. Human neuropsychology and neuroimaging studies have implicated the medial temporal lobe (MTL), including the hippocampus (HPC), in WM particularly when memory load exceeds span, yet no animal model has been established to investigate supraspan mechanisms. Here, we present a novel rodent model of supraspan memory and examine the distinct roles of dorsal and ventral HPC. Using selective NMDA lesions in mice combined with object recognition tasks and a modified radial arm maze (RAM), we manipulated memory load and strategy constraints to assess span and supraspan performance. Dorsal HPC lesions impaired object memory span, while ventral lesions spared this ability. In the RAM, span performance (number of correct arm visits before the first error) was unaffected by either lesion under allocentric conditions. However, once animals exceeded span, following the first error, here defined as the supraspan condition, both dorsal and ventral lesions caused catastrophic disorientation and error escalation. Under free-choice conditions, ventral HPC lesions selectively reduced the occurrence of trials with no errors in the first 5 choices, increased errors overall, and disrupted sequential egocentric strategies. Together, these results demonstrate that supraspan performance can be modeled in rodents, revealing a dorsal contribution to object memory under high load, a ventral contribution to egocentric spatial strategies, and a shared hippocampal role in supraspan memory performance. This paradigm provides a translational framework for investigating supraspan deficits observed in MTL patients and Alzheimers disease.

neuroscience↗

bioRxiv2025

Developmental excitation-inhibition imbalance permanently reprograms autism-relevant social brain circuits

An influential theory proposes that an imbalance between excitation and inhibition (E:I) plays a central role in the etiology of autism and related developmental disorders. However, controversy exists as to whether this imbalance is a direct causal mechanism for autism, or a compensatory response to other primary etiological factors. Using chemogenetic manipulations in neonatal mice, we show that a transient E:I imbalance during development is sufficient to permanently reprogram autism-relevant social brain circuits. Chemogenetically manipulated mice exhibit lifelong impairments in sociability, persistent dysregulation of multiple autism-risk synaptic genes, and sustained cortical hyperexcitability in adulthood. Importantly, these social impairments are robustly rescued by pharmacological inhibition of neuronal excitability. Developmental E:I imbalance also disrupts functional connectivity in social brain regions enriched for transcriptionally dysregulated genes, suggesting a convergence of transcriptional and circuit-level pathology. Finally, multivariate modelling shows that behavioral dysfunction in chemogenetically manipulated animals closely associates with disrupted connectivity between prefrontal and mesolimbic dopaminergic regions. Collectively, our findings reconcile conflicting theories in the field and point to activity-dependent transcriptional remodeling as a foundational mechanism by which transient E:I imbalance during development can cause lasting, autism-relevant circuit dysfunction.

neuroscience↗

bioRxiv2019

α-synuclein in the retina leads to degeneration of dopamine amacrine cells impairing vision

Introduction-synuclein aggregates have been identified in the retina of Parkinsons disease patients associated to vision impairment. In this study, we sought to determine the effects of -synuclein overexpression on the survival and function of dopaminergic (DA) amacrine cells in the retina.\n\nMethodsAdult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type -synuclein in the inner retina. Following systemic injections of levodopa (L-DOPA), retinal responses and visual acuity driven behavior were measured by electroretinography (ERG) and water maze task, respectively. Amacrine cells and ganglion cells were counted at 1, 2 and 3 months post-injection.\n\nResults-synuclein led to an early loss of DA cells, which was associated with the decrease of light-adapted ERG responses and visual acuity. Systemic injections of L-DOPA rescued these retinal and visual abnormalities.\n\nConclusionsThe data show that -synuclein affects dopamine neurons in the retina. The approach provides a novel accessible mode of modeling the underlying mechanisms implicated in synucleinophaties pathogenesis and for testing novel treatments.

neuroscience↗