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Polyglutamine (polyQ) diseases are a family composed of nine neurodegenerative inherited disorders (NDDs) caused by pathological expansions of cytosine-adenine-guanine (CAG) trinucleotide repeats which encode a polyQ tract in the corresponding proteins. CAG polyQ repeat expansions produce neurodegeneration via multiple downstream mechanisms; among those the neuronal activity underlying the ion channels is affected directly by specific channelopathies or indirectly by secondary dysregulation. In both cases, the altered excitability underlies to gain- or loss-of-function pathological effects. Here we summarize the repertoire of ion channels in polyQ NDDs emphasizing the biophysical features of neuronal excitability and their pathogenic role. The aim of this review is to point out the value of a deeper understanding of those functional mechanisms and processes as crucial elements for the designing and targeting of novel therapeutic avenues.

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Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by polyglutamine (polyQ) expansions in the androgen receptor (AR) gene. SBMA is characterized by selective dysfunction and degeneration of motor neurons in the brainstem and spinal cord through still unclear mechanisms in which ion channel modulation might play a central role as for other neurodegenerative diseases. The beta2-adrenergic agonist clenbuterol was observed to ameliorate the SBMA phenotype in mice and patient-derived myotubes. However, the underlying molecular mechanism has yet to be clarified. Here, we unveil that ionic current alterations induced by the expression of polyQ-expanded AR in motor neuron-derived MN-1 cells are attenuated by the administration of clenbuterol. Our combined electrophysiological and pharmacological approach allowed us to reveal that clenbuterol modifies delayed outward potassium currents. Overall, we demonstrated that the protection provided by clenbuterol restores the normal function through the modulation of KV2-type outward potassium currents, possibly contributing to the protective effect on motor neuron toxicity in SBMA.

SH-SY5Y cell line is a model for neural diseases originating from neuroblastoma, a paediatric embryonal malignancy that may differentiate and regress to a benign state. By monitoring the differentiation in single living cells, it could be possible to reach a better understanding of the process and, consequently, to develop new therapeutic approaches. In this work, we investigated the potential of Raman microspectroscopy to monitor biochemical changes in single living SH-SY5Y cells treated with a combination of retinoic acid (RA) and brain-derived neurotrophic factor to stimulate the differentiation toward a neuronal phenotype. The results show that the spectroscopic analysis is able to detect biochemical alterations consistent with the differentiation process. Moreover, we investigated also the influence of the cell culture substrate on the treatment outcome. Silicon and aluminium are 2 materials suitable for the spectroscopic analysis and of interest in neuroscience applications. Even though silicon has an ensured biocompatibility, it is subject to alterations after the treatment with RA. Aluminium revealed to be a cost-effective cell culture substrate for the RA and brain-derived neurotrophic factor treatment of SH-SY5Y cells and particularly suitable for Raman microspectroscopy. Copyright © 2018 John Wiley & Sons, Ltd.

We report a comprehensive study of the biocompatibility and neurocompatibility of titanium dioxide films (TiO2) prepared by Pulsed Microplasma Cluster Source (PMCS). This technique uses supersonic pulsed beams seeded by clusters of the metal oxide synthesized in a plasma discharge. The final stoichiometry of the TiO2 thin films is tuned changing the gas mixture, achieving stoichiometric or oxygen overstoichiometric films. All the films showed consistent biocompatibility and a spontaneous absorption of poly-d-lysine (PDL) that favors the adhesion and growth of murine cortical neurons. Moreover, the bioelectrical activity of the neuronal culture grown on the TiO2 film can be modulated by changing the chemistry of the surface. This work paves the way to develop a bio-hybrid neuromorphic device, where viable nerve cells are grown directly over a titanium dioxide film showing a network of memristors.

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a motor neuron disease caused by the expansion of a polymorphic CAG tandem repeat encoding a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA is triggered by the binding of mutant AR to its natural ligands, testosterone and dihydrotestosterone (DHT). To investigate the neuronal alterations of motor neuron cell models of SBMA, we applied patch-clamp methods to verify how polyQ expansions in the AR alter cell ionic currents. We used mouse motoneuron-derived MN-1 cells expressing normal AR (MN24Q) and mutant AR (MN100Q treated cells with vehicle EtOH and DHT). We observed a reduction of the current flux mainly at depolarizing potentials in the DHT-treated cells, while the dissection of macroscopic currents showed single different cationic currents belonging to voltage-gated channels. Also, we treated the cells with IGF-1 and PACAP, which have previously been shown to protect MN-1 cells from the toxicity of mutant AR, and we found an amelioration of the altered currents. Our results suggest that the electrophysiological correlate of SBMA is a suitable reference point for the identification of disease symptoms and for future therapeutic targets.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by expansions of a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA is associated with the progressive loss of lower motor neurons, together with muscle weakness and atrophy. PolyQ-AR is converted to a toxic species upon binding to its natural ligands, testosterone, and dihydrotestosterone (DHT). Our previous patch-clamp studies on a motor neuron-derived cell model of SBMA showed alterations in voltage-gated ion currents. Here, we identified and characterized chloride currents most likely belonging to the chloride channel-2 (ClC-2) subfamily, which showed significantly increased amplitudes in the SBMA cells. The treatment with the pituitary adenylyl cyclase-activating polypeptide (PACAP), a neuropeptide with a proven protective effect in a mouse model of SBMA, recovered chloride channel current alterations in SBMA cells. These observations suggest that the CIC-2 currents are affected in SBMA, an alteration that may contribute and potentially determine the pathophysiology of the disease.

The Italian Society for Pure and Applied Biophysics (SIBPA) held its XXIV National Congress in the beautiful seaside town of Ancona, Italy, on September 10-13, 2018. This special issue features a selection of contributions from the Congress in all areas of modern biophysics including molecular, cellular, applied, computational and nanoscale biophysics. SIBPA pursues its institutional tasks and carries on its successful promotion of biophysical disciplines at the national and international levels, also trough the consolidation of its partnership with Biophysical Chemistry and Elsevier.

The interfacing of artificial devices with biological systems is a challenging field that crosses several disciplines ranging from fundamental research (biophysical chemistry, neurobiology, material and surface science) to frontier technological application (nanotechnology, bioelectronics). The memristor is the fourth fundamental circuit element, whose electrical properties favor applications in signal processing, neural networks, and brain-computer interactions and it represents a new frontier for technological applications in many fields including the nanotechnologies, bioelectronics and the biosensors. Using multidisciplinary approaches, covering surface science, cell biology and electrophysiology, we successfully implemented a living bio-hybrid system constituted by cells adhering to films of poly(aniline) (PANI), a semiconductor polymer having memristive properties assembled with polyelectrolytes. Here we tested whether the PANI devices could support survivor, adhesion and differentiation of several cell lines, including the neuron-like SHSY5Y cells. Moreover, we performed electrophysiology on these cells showing that the biophysical properties are retained with differences occurring in the recorded ion currents. Taken together, the cell viability here reported is the key requirement to design and develop a reliable functional memristor-based bio-hybrid able to mimic neuronal activity and plasticity.

We report a comprehensive study of the biocompatibility and neurocompatibility of titanium dioxide films (TiO

The Italian Society for Pure and Applied Biophysics (SIBPA) held its XXIII National Congress in the gorgeous Tuscan town of Cortona, Italy, on September 18-21, 2016. This special issue features a selection of contributions from the Congress in the areas of molecular, applied, cellular and computational biophysics. Cutting-edge developments in nanoscale biophysics were introduced for the first time in the program. SIBPA continues its successful promotion of biophysical disciplines at the national and international levels, with added strength from its partnership with Biophysical Chemistry and Elsevier.

This Special Issue of Biophysical Chemistry presents a selection of the contributions presented at the XXII National Congress of the Italian Society of Pure and Applied Biophysics (i.e., SIBPA, Societa Italiana di Biofisica Pura ed Applicata) held on September 2014 in Palermo, Italy. Topics cover all biophysical disciplines, from molecular to cellular, to integrative biophysics giving a comprehensive view of the inter- and multi-disciplinary approach of modern biophysics. SIBPA, which turned 40 in 2013, continues to grow and attract interest.

A living bio-hybrid system has been successfully implemented. It is constituted by neuroblastic cells, the SH-SY5Y human neuroblastoma cells, adhering to a poly-anyline (PANI) a semiconductor polymer with memristive properties. By a multidisciplinary approach, the biocompatibility of the substrate has been analyzed and the functionality of the adhering cells has been investigated. We found that the PANI films can support the cell adhesion. Moreover, the SH-SY5Y cells were successfully differentiated into neuron-like cells for in vitro applications demonstrating that PANI can also promote cell differentiation. In order to deeply characterize the modifications of the bio-functionality induced by the cell-substrate interaction, the functional properties of the cells have been characterized by electrophysiology and Raman spectroscopy. Our results confirm that the PANI films do not strongly affect the general properties of the cells, ensuring their viability without toxic effects on their physiology. Ascribed to the adhesion process, however, a slight increase of the markers of the cell suffering has been evidenced by Raman spectroscopy and accordingly the electrophysiology shows a reduction at positive stimulations in the cells excitability.

Visual pigments are photosensitive receptor proteins that trigger the transduction process producing the visual excitation once they have absorbed photons. In spite of the molecular and morpho-functional complexity that has characterized the development of animal eyes and eyeless photoreceptive systems, opsin-based protein family appears ubiquous along metazoan visual systems. Moreover, in addition to classic rhodopsin photoreceptors, all Metazoa have supplementary non-visual photosensitive structures, mainly located in the central nervous system, that sense light without forming an image and that rather regulate the organism’s temporal physiology. The investigation of novel non-visual photopigments exerting extraretinal photoreception is a challenging field in vision research. Here we propose the cnidarian Hydra as a useful tool of investigation for molecular and functional differences between these pigment families. Hydra is the first metazoan owning a nervous system and it is an eyeless invertebrate showing only an extraocular photoreception, as it has no recognized visual or photosensitive structures. In this paper we provide an overview of the molecular and functional features of the opsin-based protein subfamilies and preliminary evidences in a phylogenetically old species of both image-forming and non-visual opsins. Then we give new insights on the molecular biology of Hydra photoreception and on the evolutionary pathways of visual pigments.

This Special Issue of Biophysical Chemistry includes a selection of the papers presented at the XXI Congress of the Italian Society of Pure and Applied Biophysics (i.e., SIBPA, Società Italiana di Biofisica Pura ed Applicata) held on September 2012 at the University of Ferrara, Ferrara, Italy. Topics cover all biophysical disciplines, from molecular to cellular, to integrative biophysics giving an almost comprehensive view of the interdisciplinary and multidisciplinary approaches, proper of the modern biophysics. SIBPA, which celebrates its 40th anniversary in 2013, has steadily grown and appeals to both specialists and a wider general audience.

This paper describes a method to obtain isolated photoreceptors by means of enzymatic and mechanical dissociation of the whole retina of Orconectes limosus and the application of patch‐clamp technique to these dissociated ommatidia. Several gigaseals and single‐channel currents were recorded, demonstrating the validity and suitability of the experimental protocol. The data reported provide a new element in the ≪single photoreceptor approach≫ to the study of phototransduction mechanisms in invertebrates. These results add another animal model to the few currently described in literature, in which the application of gigaseal techniques to isolated cells has proved useful in the study of ion channels gating.

Both bottom-up sensory information and top-down influences contribute to the perception processes. We studied the perceptual alternations of a multistable ambiguous pattern. We observed that it is possible to interfere on the process of the perception alternance by means of subliminal visual stimuli, which either contrast or second the previous perception. We investigated also the effect of the top-down volitional factor on the perceptual alternation. By using a combination of such top-down factor and bottom-up stimulation, we ascertained that a non-linear type of interaction occurs between the two above factors.

Two procedures aimed at a synthetic, quantitative characterization of the integrative activity in a small system of nerve cells are proposed, and applications to the buccal ganglion of the molluskAplysia are described. Both methods are based on cross-correlation evaluation. The first method processes intracellular signals simultaneously recorded from pairs of neurones, and reveals and measures the occurrence of shared synaptic input. The second method processes extracellular multiunit signals recorded by two cuff electrodes placed around one nerve, and evaluates the impulse traffic, subdivided according to direction and speed of propagation. The outcome of both methods may be used to represent the state of the system, and may provide a basis to further studies on its dynamics.

Our belief about visual system as functional tool providing only image formation, and in a common senseaninterpretativedepictionofthesurroundingrealworld,hasbeendrasticallychangedbyrecent (andoldbutrevised)achievementsonnonimage-formingvision,morewidelytermedasnonvisualphotoreceptionornonvisualphotosensitivity(NVPforboth).Classicalstudiesininvertebrateandlower vertebratespecieshavedescribed,namely,attime,extraocularorextraretinalphotosensitivecells whichexertedanancillaryroletoobviouseye-likestructuresinmeredetectionofenvironmentalirradiance(oneforalltheso-calledthirdeye,i.e.,thepinealgland,oflowervertebrateorganisms).Suchrole assumesremarkableimportanceinthoseanimalsthatlackobviouseyesorwithpooropticalapparatus.

Quella che segue è un'intervista condotta a Carlo Musio, ricercatore del settore biofisico dell'Istituto di Cibernetica "Eduardo Caianiello" del CNR, che studia i sistemi sensoriali animali, in particolare quello fotorecettoriale di Hydra, possibile precursore delle strutture visive più evolute e delle diverse modalità visive image-forming e non-image forming.

Nitric oxide (NO) is a small molecule with unconventional properties. It is found in organisms throughout the phylogenetic scale, from fungi to mammals, in which it acts as an intercellular messenger of main physiological events, or even as an intracellular messenger in invertebrates. In both vertebrates and invertebrates, NO is involved in many processes, regulated in part by cyclic guanosine monophosphate (cGMP), and reacts with different oxygen molecular species. The presence of NO in the early-diverging metazoan phylum of Cnidaria, of which Hydra represents the first known species having a nervous system, supports a role of this molecule as an ancestral neural messenger with physiological roles that remain to be largely elucidated. Therefore, our novel findings on the presence of NO in Hydra are here integrated in such a comparative frame.

Hydra’s response to a light pulse is a phase shift of the state of bioelectric activity correlated with the periodic shortening-elongation behaviour. The direction and absolute value of a phase shift depend on intensity, direction, application phase (along the periodic activity state), and wavelength of the light pulse. Repetitive pulses entrain the behavioural cycle. The period of the behavioural cycle depends on intensity and wavelength of steady background illumination; however, the light effect is not exerted isotropically along all the phases of the behavioural cycle. Inferences are drawn on light influence on the behaviour pacemaking mechanism. By using polyclonal antibodies against squid rhodopsin, an opsin-like protein has been identified in the ectodermal layer, presumably in sensory cells.

Understanding the mechanisms involved in vision and intelligent behavior of the brain, both from a natural and artificial point of view, demands more and more mul-tidisciplinary and integrated approaches of different disciplines: biophysics and neu-robiology, visual and cognitive sciences and theoretical neuroscience being only a small sample. The Brain, Vision and Artificial Intelligence Symposium 2007 (BVAI 2007, Naples, Italy, October 10-12, 2007) was the second edition of a multidisciplinary symposium that aims at gathering scientists involved in the study of basic brain, natu-ral vision, artificial vision, and artificial intelligence to promote discussion, exchange of ideas, and integration. BVAI 2007 was organized by researchers of the Institute of Cybernetics "E. Caianiello" of the Italian National Research Council, Pozzuoli, Italy (ICIB-CNR), with the support of the Italian Institute for Philosophical Studies (IISF). It was spon-sored by EBSA (European Biophysics Societies Association), GIRPR (Italian Group of Researchers in Pattern Recognition), MARS (Microgravity Advanced Research Support) Center, NEATEK SpA, PAN (Palazzo delle Arti Napoli), SINS (Italian Society for Neurosciences), and Regione Campania. Travel grants were provided for deserving young participants by EBSA, SINS and GIRPR. The symposium was held under the auspices of the AI*IA (Italian Association of Artificial Intelligence), Comune di Napoli - Assessorato alla Cultura and SIBPA (Italian Society of Pure and Applied Biophysics), and with the help of the MQC 2 (Macroscopic Quantum Coher-ence and Computing) Association. The scientific program included the participation of eight invited speakers, selected among international leading scientists in the above-mentioned fields: Michael Arbib, University of Southern California (USA), Matteo Carandini, The Smith-Kettlewell Eye Research Institute (USA), Karl Gegenfurtner, Justus-Liebig University (Ger-many), Petr Lansky, Academy of Sciences (Czech Republic), José del R. Millán, IDIAP Research Institute (Switzerland), Oliviero Stock, IRST and Fondazione Bruno Kessler (Italy), Massimo Tistarelli, University of Sassari (Italy), John K. Tsotsos, York University (Canada). Furthermore, the program included 50 contributions from worldwide participants, presented in plenary oral and poster sessions. The peer-reviewing process for the papers was performed by the Scientific Committee, includ-ing distinguished members of the scientific community, together with a number of additional reviewers, appointed by the Scientific Commitee members. The accepted contributions were selected among about 80 papers submitted to BVAI 2007. In this volume, all contributions to the symposium have been gathered according to an increasing degree of abstraction, going from the most elemental aspects of the visual processes to the most complex cognitive ones. The material has been structured into the following parts: Basic Models in Visual Sciences, Cortical Mechanism of Vision, Color Processing in Natural Vision, Action-Oriented Vision, Visual Recogni-tion and Attentive Modulation, Biometric Recognition, Image Segmentation and Rec-ognition, Disparity Calculation and Noise Analysis, Signal Identification in Neural VI Preface Models, Natural and Artificial Representation Issues in Artificial Intelligence, Mean-ing-Interaction-Emotion, Robot Navigation and Control. In our opinion, these topics can be considered the flagstones paving th e road to the ongoing integration among research in brain, vision and intelligence. We hope that this volume provides new insights and is the basis of constructive discussions. We would like to thank the invited speakers and all the contributors, the members of the Scientific Committees, including the additional reviewers and all the partici-pants. Acknowledgements are due to all our sponsors (ICIB-CNR, IISF, EBSA, GIRPR, MARS Center, NEATEK SpA, PAN, SINS, Regione Campania) for their financial contribution. We would like to acknowledge the Steering Committee mem-bers for their advice and support. A special thanks goes to the Local Committee and Secretariat members, who provided us with helpful assistance. July 2007 Francesco Mele Giuliana Raella Silvia Santillo Francesco Ventriglia

Hydra's response to a light pulse is a phase shift of the state of bioelectric activity correlated with the periodic shortening-elongation behaviour. The direction and absolute value of a phase shift depend on intensity, direction, application phase (along the periodic activity state), and wavelength of the light pulse. Repetitive pulses entrain the behavioural cycle. The period of the behavioural cycle depends on intensity and wavelength of steady background illumination; however, the light effect is not exerted isotropically along all the phases of the behavioural cycle. Inferences are drawn on light influence on the behaviour pacemaking mechanism. By using polyclonal antibodies against squid rhodopsin, an opsin-like protein has been identified in the ectodermal layer, presumably in sensory cells.

The morpho-functional organization correlated to photosensitivity in Cnidaria is that of ocelli and extraocular photoreception. Several examples of the second type of organization are reported. The photosensitivity of the cnidarian Hydra is of the extraocular (neural or dermal) type. The effects of photic stimulation (applied according to various experimental protocols: steady condition; step stimulus; single, twin, or repetitive pulses; different polarities and chromaticities of steady, step and pulse stimulation and different phases of pulse application) on the modulation of various bioelectric events linked to the periodic behaviour of the animal are reviewed. The mechanisms correlated with the photobehaviour of Hydra, as well as the problems still open on the molecular mechanisms of phototransduction, are discussed.

Increasingly higher levels of information processing contribute to the highest level of visual perception, that of object recognition. An unconscious decision-making event arising at the end of an unconscious inference process acts upon the already processed visual information resolving the ambiguity inherent to such information. In the case of multistable reversible patterns, the ambiguity is never resolved and the perception alternates among different interpretations of the visual information. The perception alternance model is used here to investigate the possibility to access into the decision-making module by means of mental activities applied in a downward direction. A will effort modifies the time patterning of the perception alternance. The will effect is higher if the decision-making mechanism is resetted also by the application of subliminal stimuli.

Cross-correlation of ‘spontaneous’ synaptic activities intracellularly recorded from pairs of neurons may be used to detect shared synaptic input, which could remain hidden in the raw data by the non-synchronized postsynaptic potentials (PSPs); besides, if a normalized cross-correlation function is adopted, the fraction of synchronized activity may be quantitatively estimated. To evaluate power and limits of this method, computer-simulated synaptic activities of pairs of neurons, in which a given percentage of PSPs were simultaneous, were subjected to this type of analysis. It was shown that percentages of shared activities as low as 4% and in some cases 2% could be revealed, with a conspicuity which was influenced by the types of associated PSPs.