Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration

Individual differences and knockout in zebrafish reveal similar cognitive effects of BDNF between teleosts and mammals

The remarkable similarities in cognitive performance between teleosts and mammals suggest that the underlying cognitive mechanisms might also be similar in these two groups. We tested this hypothesis by assessing the effects of the brain-derived neurotrophic factor (BDNF), which is critical for mammalian cognitive functioning, on fish's cognitive abilities. We found that individual differences in zebrafish's learning abilities were positively correlated with bdnf expression. Moreover, a CRISPR/Cas9 mutant zebrafish line that lacks the BDNF gene (bdnf(-/-)) showed remarkable learning deficits. Half of the mutants failed a colour discrimination task, whereas the remaining mutants learned the task slowly, taking three times longer than control bdnf(+/+) zebrafish. The mutants also took twice as long to acquire a T-maze task compared to control zebrafish and showed difficulties exerting inhibitory control. An analysis of habituation learning revealed that cognitive impairment in mutants emerges early during development, but could be rescued with a synthetic BDNF agonist. Overall, our study indicates that BDNF has a similar activational effect on cognitive performance in zebrafish and in mammals, supporting the idea that its function is conserved in vertebrates

The VIP Experiment

The Pauli Exclusion Principle (PEP) is a basic principle of Quantum Mechanics, and its validity has never been seriously challenged. However, given its importance, it is very important to check it as thoroughly as possible. Here we describe the VIP (Violation of PEP) experiment, an improved version of the Ramberg and Snow experiment (Ramberg and Snow, Phys. Lett. B238 (1990) 438); VIP shall be performed at the Gran Sasso underground laboratories, and aims to test the Pauli Exclusion Principle for electrons with unprecedented accuracy, down to $\frac{\beta^2}{2} \sim 10^{-30}$Comment: 7 pages, 5 figures, PDF only, presented by Edoardo Milotti to the conference "Quantum Theory: reconsideration of foundations-3", Vaxjo (Sweden), June, 6-11 200

New experimental limit on the Pauli Exclusion Principle violation by electrons

The Pauli Exclusion Principle (PEP) is one of the basic principles of modern physics and, even if there are no compelling reasons to doubt its validity, it is still debated today because an intuitive, elementary explanation is still missing, and because of its unique stand among the basic symmetries of physics. The present paper reports a new limit on the probability that PEP is violated by electrons, in a search for a shifted K$_\alpha$ line in copper: the presence of this line in the soft X-ray copper fluorescence would signal a transition to a ground state already occupied by 2 electrons. The obtained value, ${1/2} \beta^{2} \leq 4.5\times 10^{-28}$, improves the existing limit by almost two orders of magnitude.Comment: submitted to Phys. Lett.

VIP: An Experiment to Search for a Violation of the Pauli Exclusion Principle

The Pauli Exclusion Principle is a basic principle of Quantum Mechanics, and its validity has never been seriously challenged. However, given its fundamental standing, it is very important to check it as thoroughly as possible. Here we describe the VIP (VIolation of the Pauli exclusion principle) experiment, an improved version of the Ramberg and Snow experiment (E. Ramberg and G. Snow, {\it Phys. Lett. B} {\bf 238}, 438 (1990)); VIP has just completed the installation at the Gran Sasso underground laboratory, and aims to test the Pauli Exclusion Principle for electrons with unprecedented accuracy, down to $\beta^2/2 \approx 10^{-30} - 10^{-31}$. We report preliminary experimental results and briefly discuss some of the implications of a possible violation.Comment: Plenary talk presented by E. Milotti at Meson 2006, Cracow, 9-13 June 200

Quantitative abilities in a reptile (Podarcis sicula)

The ability to identify the largest amount of prey available is fundamental for optimizing foraging behaviour in several species. To date, this cognitive skill has been observed in all vertebrate groups except reptiles. In this study we investigated the spontaneous ability of ruin lizards to select the larger amount of food items. In Experiment 1, lizards proved able to select the larger food item when presented with two alternatives differing in size (0.25, 0.50, 0.67 and 0.75 ratio). In Experiment 2 lizards presented with two groups of food items (1 versus 4, 2 versus 4, 2 versus 3 and 3 versus 4 items) were unable to select the larger group in any contrast. The lack of discrimination in the presence ofmultiple items represents an exception in numerical cognition studies, raising the question as to whether reptiles' quantitative abilities are different from those of other vertebrate groups

Testing the Pauli Exclusion Principle for Electrons

One of the fundamental rules of nature and a pillar in the foundation of quantum theory and thus of modern physics is represented by the Pauli Exclusion Principle. We know that this principle is extremely well fulfilled due to many observations. Numerous experiments were performed to search for tiny violation of this rule in various systems. The experiment VIP at the Gran Sasso underground laboratory is searching for possible small violations of the Pauli Exclusion Principle for electrons leading to forbidden X-ray transitions in copper atoms. VIP is aiming at a test of the Pauli Exclusion Principle for electrons with high accuracy, down to the level of 10$^{-29}$ - 10$^{-30}$, thus improving the previous limit by 3-4 orders of magnitude. The experimental method, results obtained so far and new developments within VIP2 (follow-up experiment at Gran Sasso, in preparation) to further increase the precision by 2 orders of magnitude will be presented.Comment: Proceedings DISCRETE 2012-Third Symposium on Prospects in the Physics of Discrete Symmetries, Lisbon, December 3-7, 201

New experimental limit on Pauli Exclusion Principle violation by electrons (the VIP experiment)

The Pauli Exclusion Principle is one of the basic principles of modern physics and is at the very basis of our understanding of matter: thus it is fundamental importance to test the limits of its validity. Here we present the VIP (Violation of the Pauli Exclusion Principle) experiment, where we search for anomalous X-rays emitted by copper atoms in a conductor: any detection of these anomalous X-rays would mark a Pauli-forbidden transition. ] VIP is currently taking data at the Gran Sasso underground laboratories, and its scientific goal is to improve by at least four orders of magnitude the previous limit on the probability of Pauli violating transitions, bringing it into the 10**-29 - 10**-30 region. First experimental results, together with future plans, are presented.Comment: To appear in proceedings of the XLVI International Winter Meeting on Nuclear Physics, Bormio, Italy, January 20-26, 200

High sensitivity tests of the Pauli Exclusion Principle with VIP2

The Pauli Exclusion Principle is one of the most fundamental rules of nature and represents a pillar of modern physics. According to many observations the Pauli Exclusion Principle must be extremely well fulfilled. Nevertheless, numerous experimental investigations were performed to search for a small violation of this principle. The VIP experiment at the Gran Sasso underground laboratory searched for Pauli-forbidden X-ray transitions in copper atoms using the Ramberg-Snow method and obtained the best limit so far. The follow-up experiment VIP2 is designed to reach even higher sensitivity. It aims to improve the limit by VIP by orders of magnitude. The experimental method, comparison of different PEP tests based on different assumptions and the developments for VIP2 are presented.Comment: 6 pages, 3 figures, Proceedings DISCRETE2014 Conferenc

Mutations in blind cavefish target the light-regulated circadian clock gene, period 2

Light represents the principal signal driving circadian clock entrainment. However, how light influences the evolution of the clock remains poorly understood. The cavefish Phreatichthys andruzzii represents a fascinating model to explore how evolution under extreme aphotic conditions shapes the circadian clock, since in this species the clock is unresponsive to light. We have previously demonstrated that loss-of-function mutations targeting non-visual opsins contribute in part to this blind clock phenotype. Here, we have compared orthologs of two core clock genes that play a key role in photic entrainment, cry1a and per2, in both zebrafish and P. andruzzii. We encountered aberrantly spliced variants for the P. andruzzii per2 transcript. The most abundant transcript encodes a truncated protein lacking the C-terminal Cry binding domain and incorporating an intronic, transposon-derived coding sequence. We demonstrate that the transposon insertion leads to a predominantly cytoplasmic localization of the cavefish Per2 protein in contrast to the zebrafish ortholog which is distributed in both the nucleus and cytoplasm. Thus, it seems that during evolution in complete darkness, the photic entrainment pathway of the circadian clock has been subject to mutation at multiple levels, extending from opsin photoreceptors to nuclear effectors