Bravin, A. | Search bioRxiv

bioRxiv2019

The structure of behavioral variation within a genotype

Individual animals vary in their behaviors. This is true even when they share the same genotype and were reared in the same environment. Clusters of covarying behaviors constitute behavioral syndromes, and an individuals position along such axes of covariation is a representation of their personality. Despite these conceptual frameworks, the structure of behavioral covariation within a genotype is essentially uncharacterized and its mechanistic origins unknown. Passing hundreds of inbred Drosophila individuals through an experimental pipeline that captured hundreds of behavioral measures, we found correlations only between sparse pairs of behaviors. Thus, the space of behavioral variation has many independent dimensions. Manipulating the physiology of the brain, and specific neural populations, altered specific correlations. We also observed that variation in gene expression can predict an individuals position on some behavior axes. This work represents the first steps in understanding the biological mechanisms determining the structure of behavioral variation within a genotype.

neuroscience↗

bioRxiv2019

Chronic pain alters microvascular architectural organization of somatosensory cortex

Chronic pain (CP) represents a complex pathology profoundly involving both neural and glial compartments of the central nervous system. While most CP studies have also investigated the macroscopic brain vascular system, its microstructural architecture still remains largely unexplored. Further, the adaptive modifications of the vascular microstructure as consequence of diseases or pathological insults, did not receive adequate attention. Here we show microtomographic signs of diffuse and conspicuous microvascular neogenesis in somatosensory cortex of CP animal models already peaking at 15 days from the model instantiation. Progressive fading of this microvessel neogenesis then ensued in the next six months yet maintaining higher vascular density with a preserved small fraction of them. Due to the important consequences on the neuron-glial-vessel arrangements and on the resulting metabolic and functional disorders of the local networks, novel additional scenarios of CP are thus conceivable with profound consequences of potential future CP diagnostic and therapeutic appraisals.

neuroscience↗

bioRxiv2019

Removal of behavioural and electrophysiological signs of chronic pain by in vivo microsections of rat somatosensory cortex with parallel X-ray microbeams

Chronic pain (CP) is a condition characterized by a wide spectrum of clinical signs and symptoms, missing a sound modelling at the neuronal network scale. Recently, we presented a general theory showing common electrophysiological traits in different CP rat models, i.e. a collapse of relevant functional connectivity network properties, such as modularity, in the somatosensory thalamo-cortical (TC) network. In this work, we preliminary investigated by an in silico accurate simulator of the six-layer mammalian cortical networks that evidenced the crucial collapse of network modularity in CP simulated conditions and the consequent reduction of network adaptive processes. On this track, in studies on CP experimental animals affected by sciatic nerve multiple ligature (Bennett-Xie model), by synchrotron-generated X-ray microbeam (MB) irradiations (7 parallel beams, 100um width), we targeted in vivo the CP involved hindlimb somatosensory projection cortex that, because of the doses radiation (360 Gy, peak at each beam), non-invasively produced fast and precise tissue destruction along the 7 beam projections. These parcellated the cortical tissue and restored the cortical network statistics related to modularity and information processing efficiency as evidenced from post irradiation in vivo electrophysiological recordings. In addition, by MB treatment there was an ensuing removal of behavioral signs of allodynia and hyperalgesia accompanied by recovered normal gait schemes yet preserving the normal sensory thresholds of the experimental rats up to three months after the MB irradiation. Finally, novel and unprecedented therapeutic appraisals for CP are devised. Significance StatementChronic pain (CP) is an excruciating condition with severe effects on patients life. Apart from many clinical and experimental studies no current theory on CP is generally accepted. Recently, we proposed a general theory of CP in experimental animals as characterized by strong alteration of the connections among neurons in different brain regions. We show here on in silico simulations that specific connectivity changes in the somatosensory cortex recover the lost functional integrity. Concurrently, in experimental animals, we re-modulated, in vivo, some anatomical connections of the somatosensory cortex by extremely thin synchrotron generated X-ray microbeam irradiations. The resulting behavioral and electrophysiological signs of CP disappeared yet maintaining normal sensory responses. No adverse or pathological effects on blank animals were observable.

neuroscience↗