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Dalla, S.

Publications and source records attributed to Dalla, S..

2 recordsLinked to original sources

Post-Ischemic Reorganization of Sensory Responses in Cerebral Cortex

Sensorimotor integration is critical for generating skilled, volitional movements. While stroke tends to impact motor function, there are also often associated sensory deficits that contribute to overall behavioral deficits. Because many of the cortico-cortical projections participating in the generation of volitional movement either target or pass-through primary motor cortex (in rats, caudal forelimb area; CFA), any damage to CFA can lead to a subsequent disruption in information flow. As a result, the loss of sensory feedback is thought to contribute to motor dysfunction even when sensory areas are spared from injury. Previous research has suggested that the restoration of sensorimotor integration through reorganization or de novo neuronal connections is important for restoring function. Our goal was to determine if there was crosstalk between sensorimotor cortical areas with recovery from a primary motor cortex injury. First, we investigated if peripheral sensory stimulation would evoke responses in the rostral forelimb area (RFA), a rodent homologue to premotor cortex. We then sought to identify whether intracortical microstimulation-evoked activity in RFA would reciprocally modify the sensory response. We used seven rats with an ischemic lesion of CFA. Four weeks after injury, the rats forepaw was mechanically stimulated under anesthesia and neural activity was recorded in the cortex. In a subset of trials, a small intracortical stimulation pulse was delivered in RFA either individually or paired with peripheral sensory stimulation. Our results point to post-ischemic connectivity between premotor and sensory cortex that may be related to functional recovery. Premotor recruitment during the sensory response was seen with a peak in spiking within RFA after the peripheral solenoid stimulation despite the damage to CFA. Furthermore, stimulation evoked activity in RFA modulated and disrupted the sensory response in sensory cortex, providing additional evidence for the transmission of premotor activity to sensory cortex and the sensitivity of sensory cortex to premotor cortexs influence. The strength of the modulatory effect may be related to the extent of the injury and the subsequent reshaping of cortical connections in response to network disruption.

neuroscience↗

Different combinations of insect Na,K-ATPase α- and β-subunit paralogs enable fine tuning of toxin resistance and enzyme kinetics

BackgroundCardiac glycosides are known to fatally inhibit the Na,K-ATPase throughout the animal kingdom. Several animals, however, evolved target-site insensitivity by substitutions in the otherwise highly conserved cardiac glycoside binding pocket located on the Na,K-ATPase -subunit. The minimal functional enzyme consist of an - and a {beta}-subunit, the latter considered mainly as a chaperone responsible for correct folding and membrane integration. We here analyze resistance to cardiac glycosides and kinetic properties of different Na,K-ATPase /{beta}-combinations of the large milkweed bug, Oncopeltus fasciatus. These insects have adapted to high concentrations of cardiac glycosides in their food plants via several rounds of Na,K-ATPase gene duplications followed by differential resistance conferring substitutions and subfunctionalization of the enzymes. ResultsTo investigate their characteristics we expressed nine combinations of O. fasciatus Na,K-ATPase /{beta}-sunbunits (three each) in Sf9 cells and tested them with two structurally distinct cardiac glycosides, calotropin, a host plant compound, and ouabain, a commonly used toxin. Differences in the number and identity of amino acid substitutions in the cardiac glycoside binding site resulted in large differences in activity and toxin resistance of the three -subunits. The enzymes kinetics were also influenced by the {beta}-subunits leading to increased activities (C{beta}3) or altered resistances. The host plant toxin calotropin proved to be a much more potent inhibitor than ouabain for the phylogenetically oldest C based enzymes. This effect was compensated for in the B and A based enzymes with A{beta}1 having higher resistance against calotropin than against ouabain. ConclusionThe originally higher inhibitory potency of the host compound calotropin supports a coevolutionary escalation of plant defenses and herbivore tolerance mechanisms. For the bugs the possession of multiple paralogs improved adaptation to plant toxins in a stepwise manner and mitigates pleiotropic effects by a compromise between ion pumping activity and resistance.

evolutionary biology↗