The architecture of information processing in biological systems

Biological systems process information at different scales and adapt to their changing environment. Informed both by experimental observations and theoretical constraints, we propose a chemical model for sensing that incorporates energy consumption, information storage, and negative feedback. We show that a biochemical architecture enclosing these minimal mechanisms leads to the emergence of dynamical memory and adaptation. Crucially, adaptation is associated with both an increase in the mutual information between external and internal variables and a reduction of dissipation of the internal chemical processes. By simultaneously minimizing energy consumption and maximizing information, we find that far-from-equilibrium sensing dominates in the low-noise regime. Our results, in principle, can be declined at different biological scales. We employ our model to shed light on large-scale neural adaptation in zebrafish larvae under repeated visual stimulation. We find striking similarities between predicted and observed behaviors, capturing the emergent adaptation of neural response. Our framework draws a path toward the unraveling of the essential ingredients that connect information processing, adaptation, and memory in biological systems

Simultaneous two-photon imaging and photo-stimulation with structured light illumination.

Holographic microscopy is increasingly recognized as a promising tool for the study of the central nervous system. Here we present a "holographic module", a simple optical path that can be combined with commercial scanheads for simultaneous imaging and uncaging with structured two-photon light. The present microscope is coupled to two independently tunable lasers and has two principal configurations: holographic imaging combined with galvo-steered uncaging and holographic uncaging combined with conventional scanning imaging. We applied this flexible system for simultaneous two-photon imaging and photostimulation of neuronal cells with complex light patterns, opening new perspectives for the study of brain function in situ and in vivo

Targeted optogenetic stimulation to study the computational properties in neuronal ensembles recorded by multi-electrode devices

Micro-electrode array (MEA) technology has been exploited as a powerful tool for providing distributed information on learning, memory and information processing in cultured neuronal tissue, enabling an experimental perspective from the single cell level up to the scale of complex biological networks. An integral part in the use of MEAs involves the need to apply a local stimulus to stimulate or modulate the activity of certain regions of the tissue down to the single neuron level. Currently, this presents various limitations due to the low spatial resolution of the electrical stimulation. The recent development of optogenetic probes enables for the opportunity to switch from a full electrical paradigm to a combination of a reliable optical stimulation, including excitation and inhibition, coupled to large scale recordings based on MEA. In order to take full advantage from the expression of such optical tools, the capability of properly shaping the optical stimulation pattern has to be developed to fit at the same time either the single neuron targeting or multi site/large area stimulation. The design of a versatile patterned light projection device is an essential step towards this goal. Digital micro-mirrors devices (DMDs) spatial light modulators became recently available a tools for spatial mapped fluorescence measurements, photo-patterning, molecule uncaging and high resolution imaging. Here we describe a two-wavelength spatial light projection system for real-time closed loop modulation of neuronal activity, which is able to trigger a specific protocol of optical stimulation (space, time, wavelengths) by properly configuring the DMD upon detection of typical patterns (space and time) of electrical activation recorded with MEA. By adopting such an approach, it will be possible to better understand the fundamental mechanisms underlying the propagation and processing of the information in distinct neuronal subareas or subpopulations and their specific roles within in-vitro or ex-vivo neuronal networks

A novel sensor for ion electron emission microscopy

Abstract An ion electron emission microscope (IEEM) to be installed at the SIRAD heavy ion irradiation facility at the 15 MV tandem accelerator of the INFN Legnaro laboratory (Italy) will be used to characterize the sensitivity of electronic devices to single event effects (SEE) to ion impacts with micrometric lateral resolutions. The secondary electrons emitted by ion impacts from the target surface are transported and focused by an electron microscope onto a micro-channel plate (MCP) detector coupled to a fast phosphor. The luminous signal is then detected by a position sensitive photon detector located outside the vacuum chamber. The high repetition rates and high spatial resolution, required to temporally distinguish ion impacts for SEE studies and avoid degrading of the initial resolution of the IEEM and MCP are met by the system, presented here for the first time, based on two orthogonal linear CCDs

New Approaches towards Organic Photodetection and Bio-Integration

Organic semiconductors technology has only recently started to merge with biology and medicine, especially in the field of polymeric coatings as protective layers for artificial devices. Very few examples, however, report the use of semiconducting polymers as active materials in the bio-environment. Here we demonstrate hybrid, solid-liquid photodiodes, in which a semiconducting polymer film (poly[2-methoxy-5-(2’-ethylhexyloxy)-p-phenylene vinylene], MEH-PPV) is deposited on an Indium-Tin Oxide anode and contacted to various liquid ionic cathodes (water, saline solutions, physiological buffers, cell-culturing media), instead of commonly used metallic cathodes. In the double-phase device, in contrast to conventional photodiodes, ionic transport inside the liquid medium plays a key-role. Remarkably, the conductance type changes from mainly electronic, in the polymer film, to ionic, at the semiconductor-electrolyte interface and in the liquid phase. Such unconventional devices display good behaviors in photovoltaic regime. We give a complete opto-electronic characterization of the devices, discuss the peculiar properties which stem from the hybrid solid-liquid nature and propose a physical-chemical explanation of the working principle. The main differences between hybrid and conventional photodiodes, related to interface phenomena between the polymer film and the cathode, are extensively investigated as well; to this goal, we study the effect of ionic liquid media onto the photophysics of conjugated polymers, comparing the behavior of polymer bulk and polymer-liquid interfaces by means of several time-domain optical probes. Additionally, we demonstrate that this hybrid device can be an interface for communicating with a neuronal network grown on top of the organic layer. The organic semiconductor behaves as photo-window for an unconventional and unprecedented organic-bio communication protocol

02/28/1984 - Cager Could Come Up With Upset

We propose the realization of a compact fully-passive biotelemetry tag composed of a high-electron mobility transistor (HEMT) connected to a wireless link. The Gallium Arsenide based gateless HEMT serves both as the environmental sensing element and as the amplitude modulator of the carrier signal received by the antenna. A prototype demonstrator operating in the MHz range has been developed: it consists of an array of transistors with different gate geometries and two spiral loop resonators implementing the wireless link. More specifically, one resonator (Tag-resonator) is connected to the array of transistors, while the other one (Reader-resonator) is connected to a power generator/reader device; the wireless link uses the magnetic coupling between the two resonators. Experimental results demonstrate that the reader-resonator exhibits an intensity modulation of the resonance dip depending on the voltage applied to the HEMT gate. These results will be used as a guideline for the realization of biocompatible sub-millimeter tags operating in the Gigahertz frequency range

The three-electrode device: A new frontier for the in utero electroporation

The understanding of brain function requires the development of new methods to perturb and track distinct neuronal populations in the developing and adult central nervous system. Over the past ten years, in utero electroporation (IUE) has arisen as an extremely powerful tool to transfect and manipulate neuronal precursor cells of the parietal-cortex and their progeny in vivo. Although this technique has tremendous potentialities in targeting numerous brain areas, the results obtained so far have been generally hindered by low reliability of transfection in some regions and by the physical impossibility to reach other regions. Here, we present an innovative IUE configuration, which allows highly reliable transfection at various brain locations, including regions and cell types never targeted before. Our device, based on the usage of three independent electrodes upon an easy and highly reliable re-orientation of the electrode’s positions and polarities, allows consistent expression of genes of interest in an array of brain areas including the hippocampus, the visual and motor cortices, and the cerebellum. Moreover, depending on the developmental stage of the embryos, it is possible to target distinct neuronal cell types, which may be particularly relevant in the cerebellum. The importance of such a tool in comparison to other methods arises in those particular applications where tissues and circuits integrity are essential points, and in those where traditional electroporation configuration is the limiting step of the experimental approach

High-performance and site-directed in utero electroporation by a triple-electrode probe

In utero electroporation is a powerful tool to transfect and manipulate neural-precursor cells of the rodent parietal cortex and their progeny in vivo. Although this technique can potentially target numerous brain areas, reliability of transfection in some brain regions is low or physical access is limited. Here we present a new in utero electroporation configuration based on the use of three electrodes, the relative position and polarities of which can be adjusted. The technique allows easy access and exceedingly reliable monolateral or bilateral transfection at brain locations that could only be sporadically targeted before. By improvement in the efficiency of the electrical field distribution, demonstrated here by a mathematical simulation, the multi-electrode configuration also extends the developmental timeframe for reliable in utero electroporation, allowing for the first time specific transfection of Purkinje cells in the rat cerebellum

A “glympse” into neurodegeneration: Diffusion MRI and cerebrospinal fluid aquaporin‐4 for the assessment of glymphatic system in Alzheimer's disease and other dementias

The glymphatic system (GS) is a whole‐brain perivascular network, consisting of three compartments: the periarterial and perivenous spaces and the interposed brain parenchyma. GS dysfunction has been implicated in neurodegenerative diseases, particularly Alzheimer's disease (AD). So far, comprehensive research on GS in humans has been limited by the absence of easily accessible biomarkers. Recently, promising non‐invasive methods based on magnetic resonance imaging (MRI) along with aquaporin‐4 (AQP4) quantification in the cerebrospinal fluid (CSF) were introduced for an indirect assessment of each of the three GS compartments. We recruited 111 consecutive subjects presenting with symptoms suggestive of degenerative cognitive decline, who underwent 3 T MRI scanning including multi‐shell diffusion‐weighted images. Forty nine out of 111 also underwent CSF examination with quantification of CSF‐AQP4. CSF‐AQP4 levels and MRI measures—including perivascular spaces (PVS) counts and volume fraction (PVSVF), white matter free water fraction (FW‐WM) and mean kurtosis (MK‐WM), diffusion tensor imaging analysis along the perivascular spaces (DTI‐ALPS) (mean, left and right)—were compared among patients with AD (n = 47) and other neurodegenerative diseases (nAD = 24), patients with stable mild cognitive impairment (MCI = 17) and cognitively unimpaired (CU = 23) elderly people. Two runs of analysis were conducted, the first including all patients; the second after dividing both nAD and AD patients into two subgroups based on gray matter atrophy as a proxy of disease stage. Age, sex, years of education, and scanning time were included as confounding factors in the analyses. Considering the whole cohort, patients with AD showed significantly higher levels of CSF‐AQP4 (exp(b) = 2.05, p = .005) and FW‐WM FW‐WM (exp(b) = 1.06, p = .043) than CU. AQP4 levels were also significantly higher in nAD in respect to CU (exp(b) = 2.98, p < .001). CSF‐AQP4 and FW‐WM were significantly higher in both less atrophic AD (exp(b) = 2.20, p = .006; exp(b) = 1.08, p = .019, respectively) and nAD patients (exp(b) = 2.66, p = .002; exp(b) = 1.10, p = .019, respectively) compared to CU subjects. Higher total (exp(b) = 1.59, p = .013) and centrum semiovale PVS counts (exp(b) = 1.89, p = .016), total (exp(b) = 1.50, p = .036) and WM PVSVF (exp(b) = 1.89, p = .005) together with lower MK‐WM (exp(b) = 0.94, p = .006), mean and left ALPS (exp(b) = 0.91, p = .043; exp(b) = 0.88, p = .010 respectively) were observed in more atrophic AD patients in respect to CU. In addition, more atrophic nAD patients exhibited higher levels of AQP4 (exp(b) = 3.39, p = .002) than CU. Our results indicate significant changes in putative MRI biomarkers of GS and CSF‐AQP4 levels in AD and in other neurodegenerative dementias, suggesting a close interaction between glymphatic dysfunction and neurodegeneration, particularly in the case of AD. However, the usefulness of some of these biomarkers as indirect and standalone indices of glymphatic activity may be hindered by their dependence on disease stage and structural brain damage