Ocean planning for species on the move provides substantial benefits and requires few trade-offs.

Societies increasingly use multisector ocean planning as a tool to mitigate conflicts over space in the sea, but such plans can be highly sensitive to species redistribution driven by climate change or other factors. A key uncertainty is whether planning ahead for future species redistributions imposes high opportunity costs and sharp trade-offs against current ocean plans. Here, we use more than 10,000 projections for marine animals around North America to test the impact of climate-driven species redistributions on the ability of ocean plans to meet their goals. We show that planning for redistributions can substantially reduce exposure to risks from climate change with little additional area set aside and with few trade-offs against current ocean plan effectiveness. Networks of management areas are a key strategy. While climate change will severely disrupt many human activities, we find a strong benefit to proactively planning for long-term ocean change.

Reduced postsynaptic GABAA receptor number and enhanced gaboxadol induced change in holding currents in Purkinje cells of the dystrophin-deficient mdx mouse.

UNLABELLED: Duchenne muscular dystrophy (DMD) is caused by the absence of a functional transcript of the protein dystrophin. DMD is associated with a range of cognitive deficits that are thought to result from a lack of the protein dystrophin in brain structures involved in cognitive functions. The CNS involvement extends to an impairment of cognitive abilities, with many DMD boys having significant reduction in IQ. In the cerebellum, dystrophin is normally localized at the postsynaptic membrane of GABAergic synapses on Purkinje cells. Here, we investigate the effect of an absence of dystrophin on the number of GABA(A) channels located at the synapse in cerebellar Purkinje cells of the dystrophin-deficient mdx mouse. Whole-cell patch-clamp recordings of spontaneous miniature inhibitory postsynaptic currents (mIPSCs) were performed in cerebellar slices from mdx and littermate control mice. Our results showed that the number of receptors at GABAergic synapses in the cerebellar Purkinje cell was significantly reduced in mdx mice (38.38 ± 2.95) compared to littermate controls (53.03 ± 4.11). Furthermore, when gaboxadol was added to the bath, the change in holding current in mdx mice was significantly enhanced (65.01 ± 5.89pA) compared to littermate controls (37.36 ± 3.82pA). The single channel unitary conductance and the rise and decay time of mIPSCs were not significantly different in these two groups of mice, indicating that those GABA(A) channels located at the postsynaptic sites in the mdx mice function normally. CONCLUSION: There is a reduction in the number of functional receptors localized at GABAergic synapses in the cerebellar Purkinje cells of dystrophin-deficient mdx mice and an increase in a gaboxadol induced holding current, which is evidence for an increase in extrasynaptic GABA(A) receptors in mdx mice. We hypothesize that the absence of dystrophin, from mdx Purkinje cells, reduces the number of post-synaptic GABA(A) receptors and as a result there is an increase in extrasynaptic receptors. If similar changes occur in the CNS in boys with DMD, it will impact on the function of neural networks and may contribute to some of the motor, behavioral and cognitive impairment apparent in many boys with DMD.

Responses of starburst amacrine cells to prosthetic stimulation of the retina.

Recent advances in the design and development of retinal implants have made these devices a promising therapeutic strategy for restoring sight to the blind. Over the last decade a plethora of studies have investigated the responses of the retinal ganglion cells (RGCs) to electrical stimulation under a variety of stimulus configurations. Similar to the RGCs, the amacrine cells also survive in large numbers following retinal neural degeneration. However, with the exception of two previous reports, where the responses of the amacrine cells were measured indirectly, these cells have thus far received little attention in the context of prosthetic stimulation. In this study we focused on the starburst amacrine cells (SACs), a particularly well-characterized amacrine cell among the approximately two-dozen types known to exist in the retina. Using whole-cell patch clamp recordings in the whole-mount rabbit retina, we investigated the temporal responses of the SACs following subretinal biphasic pulse stimulation. These cells responded to the stimuli with oscillatory membrane potentials that lasted for tens to hundreds of milliseconds, with the response amplitude increasing as a function of stimulus strength. Furthermore, the SAC responses originated primarily from the presynaptic inputs they receive, rather than through direct activation of these cells by the electrical stimuli.

Discrete cortical responses from multi-site supra-choroidal electrical stimulation in the feline retina.

Exploration into electrical stimulation of the retina has thus far focussed primarily upon the development of prostheses targeted at one of two sites of intervention - the epi- and sub-retinal surfaces. These two approaches have sound, logical merit owing to their proximity to retinal neurons and their potential to deliver stimuli via the surviving retinal neural networks respectively. There is increasing evidence, however, that electric field effects, electrode engineering limitations, and electrode-tissue interactions limit the spatial resolution that once was hoped could be elicited from electrical stimulation at epi- and sub-retinal sites. An alternative approach has been proposed that places a stimulating electrode array within the supra-choroidal space - that is, between the sclera and the choroid. Here we investigate whether discrete, cortical activity patterns can be elicited via electrical stimulation of a feline retina using a custom, 14 channel, silicone rubber and Pt electrode array arranged in two hexagons comprising seven electrodes each. Cortical responses from Areas 17/18 were acquired using a silicon-based, multi-channel, penetrating probe developed at IMTEK, University of Freiburg, within the European research project NeuroProbes. Multi-unit spike activity was recorded in synchrony with the presentation of electrical stimuli. Results show that distinct cortical response patterns could be elicited from each hexagon separated by 1.8 mm (center-to-center) with a center-to-center electrode spacing within each hexagon of 0.55 mm. This lends support that higher spatial resolution may also be discerned.

Experimental validation of a polyvinylidene fluoride sensing element in a tactile sensor.

A tactile sensor for robotic applications is described, inspired by the mechanoreceptors in the glabrous skin of the human hand, in order to replicate the sensory function of both slow adapting and fast adapting mechanoreceptors. Strain gauges were used for the slow adapting receptors, and polyvinylidene fluoride (PVDF) film was used to replicate the fast adapting receptors. A finite element analysis (FEA) model was used to predict the output response of the PVDF film, and verified experimentally. The PVDF film was observed to respond linearly to mechanical stress and exhibited increased gain at higher frequencies. "Ramp and hold" stimuli were applied to the tactile unit sensor, and the PVDF film only responded at contact onset and offset, similar to the response of fast adapting receptors. The PVDF acted as a dynamic sensing element for the proposed tactile sensor unit.

A transparent electrode array for simultaneous cortical potential recording and intrinsic signal optical imaging.

Intrinsic signal optical imaging (ISOI) is a technique that enables researchers to relate changes in cortical activity in response to stimuli by measuring changes in hemoglobin oxygenation and local blood volume. As the time course of these changes - local blood volume in particular - is of the order of seconds, the neural activity that initiates these changes is only indirectly acquired in ISOI. To better correlate these events, it is beneficial to simultaneously record both the evoked cortical potentials and ISOI. In this study we present a novel, transparent, recording array that allows the combination of optical imaging with electrical recordings without the use of metal electrodes in the observation field. Pilot data were recorded after visual and electrical stimuli of the eye to prove the concept.

Elastic and viscoelastic properties of porcine subdermal fat using MRI and inverse FEA.

There is a scarcity of investigation into the mechanical properties of subdermal fat. Recently, progress has been made in the determination of subdermal stress and strain distributions. This requires accurate constitutive modelling and consideration of the subdermal tissues. This paper reports the results of a study to estimate non-linear elastic and viscoelastic properties of porcine subdermal fat using a simple constitutive model. High-resolution magnetic resonance imaging (MRI) was used to acquire a time series of coincident images during a confined indentation experiment. Inverse finite element analysis was used to estimate the material parameters. The Neo Hookean model was used to represent the elastic behaviour (µ = 0.53 ± 0.31 kPa), while a single-element Prony series was used to model the viscoelastic response (α = 0.39 ± 0.03, τ = 700 ± 255 s).

Direct activation of retinal ganglion cells with subretinal stimulation.

Recent advances in the design and implementation of vision prostheses have made these devices a promising therapeutic option for restoring sight to blind patients in the near future. The success of vision prostheses in providing clinically useful vision, however, depends critically on our understanding of the retinal neural mechanisms evoked during electrical stimulation, and how these mechanisms can be controlled precisely to elicit the desired visual percept. We demonstrate here that subretinal stimulation can reliably elicit stimulus- locked short latency (< or = 2 ms) responses. To our knowledge, this is the first report of such responses using the subretinal paradigm. These responses could be readily distinguished from within the stimulus artifacts using cell-attached extracellular recording or whole-cell patch clamp. The thresholds for these short latency responses were determined for ON, OFF and ON- OFF type retinal ganglion cell classes across cathodic biphasic pulses of 0.1-5.0ms. No significant difference was found for the mean latency and the threshold for the different cell types over the pulse range tested.

Experimental validation of a tactile sensor model for a robotic hand.

We describe a tactile sensor for a robotic hand, based on the mechanoreceptors in the glabrous skin of the human hand to replicate the sensory function of both slow adapting and fast adapting receptors. Strain gauges are used for the slow adapting receptors, and polyvinylidene fluoride (PVDF) film was used to replicate the function of the fast adapting receptors. One unit sensor consisted of four strain gauges and a single PVDF film, embedded beneath a square protrusion. The protrusion helped localize the applied force onto the region or 'receptive field' of the sensing unit. Strain gauges were orientated to enable the unit sensor to identify the tri-axial force components. Multiple linear regression was used to predict the components of force. The regression model with interaction terms gave good prediction with mean percentage errors of less than 15% for each force component.

Rehabilitation regimes based upon psychophysical studies of prosthetic vision.

Human trials of prototype visual prostheses have successfully elicited visual percepts (phosphenes) in the visual field of implant recipients blinded through retinitis pigmentosa and age-related macular degeneration. Researchers are progressing rapidly towards a device that utilizes individual phosphenes as the elementary building blocks to compose a visual scene. This form of prosthetic vision is expected, in the near term, to have low resolution, large inter-phosphene gaps, distorted spatial distribution of phosphenes, restricted field of view, an eccentrically located phosphene field and limited number of expressible luminance levels. In order to fully realize the potential of these devices, there needs to be a training and rehabilitation program which aims to assist the prosthesis recipients to understand what they are seeing, and also to adapt their viewing habits to optimize the performance of the device. Based on the literature of psychophysical studies in simulated and real prosthetic vision, this paper proposes a comprehensive, theoretical training regime for a prosthesis recipient: visual search, visual acuity, reading, face/object recognition, hand-eye coordination and navigation. The aim of these tasks is to train the recipients to conduct visual scanning, eccentric viewing and reading, discerning low-contrast visual information, and coordinating bodily actions for visual-guided tasks under prosthetic vision. These skills have been identified as playing an important role in making prosthetic vision functional for the daily activities of their recipients.

A wearable real-time image processor for a vision prosthesis.

Rapid progress in recent years has made implantable retinal prostheses a promising therapeutic option in the near future for patients with macular degeneration or retinitis pigmentosa. Yet little work on devices that encode visual images into electrical stimuli have been reported to date. This paper presents a wearable image processor for use as the external module of a vision prosthesis. It is based on a dual-core microprocessor architecture and runs the Linux operating system. A set of image-processing algorithms executes on the digital signal processor of the device, which may be controlled remotely via a standard desktop computer. The results indicate that a highly flexible and configurable image processor can be built with the dual-core architecture. Depending on the image-processing requirements, general-purpose embedded microprocessors alone may be inadequate for implementing image-processing strategies required by retinal prostheses.

Focal activation of the feline retina via a suprachoroidal electrode array.

This paper presents the results of the first investigations into the use of bipolar electrical stimulation of the retina with a suprachoroidal vision prosthesis, and the effects of different electrode configurations on localization of responses on the primary visual cortex. Cats were implanted with electrodes in the suprachoroidal space, and electrically evoked potentials were recorded on the visual cortex. Responses were elicited to bipolar and monopolar stimuli, with each stimulating electrode coupled with either six-return electrodes, two-return electrodes, or a single-return electrode. The average charge threshold to elicit a response with bipolar stimulation and six-return electrodes was 76.47+/-8.76 nC. Bipolar stimulation using six-return electrodes evoked responses half the magnitude of those elicited with a single or two-return electrodes. Monopolar stimulation evoked a greater magnitude, and area of cortical activation than bipolar stimulation. This study showed that suprachoroidal, bipolar stimulation can elicit localized activity in the primary visual cortex, with the extent of localization and magnitude of response dependent on the electrode configuration.

Multichannel surface recordings on the visual cortex: implications for a neuroprosthesis.

Using a multi-channel platinum surface electrode array, recordings from cat primary visual cortex were obtained in response to visual stimuli, and electrical stimuli delivered using the elements of the array itself. Neural responses to electrical stimuli were consistent, regardless of stimulus polarity or leading phase (biphasic), although thresholds were lower for monophasic than biphasic pulses. Both visual and electrical stimuli reliably evoked responses with characteristic components, which interacted with each other in a nonlinear summation showing first facilitation then suppression during the window of interaction. The chronaxie for eliciting threshold cortical responses was about 100 mus, and the charge density with a pulse width of 50-100 mus was around 55 muC cm(-2). These data form the basis of understanding the types of cortical responses to stimuli delivered by devices suitable for chronic implantation.

GABA(A) receptor expression and inhibitory post-synaptic currents in cerebellar Purkinje cells in dystrophin-deficient mdx mice.

1. Duchenne muscular dystrophy (DMD) is the second most common fatal genetic disease and arises as a consequence of an absence or disruption of the protein dystrophin. In addition to wasting of the skeletal musculature, boys with DMD have a significant degree of cognitive impairment. 2. We show here that there is no difference between littermate control and mdx mice (a murine model of DMD) in the overall expression of the GABA(A) receptor a1-subunit, supporting the suggestion that it is the clustering at the synapse that is affected and not the expression of the GABA(A) receptor protein. 3. We report a significant reduction in both the frequency and amplitude of spontaneous inhibitory post-synaptic currents in cerebellar Purkinje cells of mdx mice compared with littermate controls, consistent with the reported reduction in the number and size of GABA(A) receptor clusters immunoreactive for a1- and a2-subunits at the post-synaptic densities. 4. These results may explain some of the behavioural problems and cognitive impairment reported in DMD.

Efficacy of supra-choroidal, bipolar, electrical stimulation in a vision prosthesis.

The key to successful, clinical application of therapeutic neurostimulators lies primarily with the safety and efficacy of their electrode-tissue interfaces. The authors posit that for electrical stimulation of the visual system, supra-choroidal electrode placement provides a safe, stable and readily-accessible site for implantation and the provision of electrical stimulation. The present paper explores the efficacy of supra-choroidal electrical stimulation of retinal neurons. Based upon recordings made with surface electrodes placed on the primary visual cortex, areas of activation in the cortex were shown to change when different areas on the supra-choroidal space were stimulated. Finally, the threshold to elicit a response from neurons in the visual cortex, was found to be 77.55 +/- 29.85 nC.

Suppression of vibrotactile discrimination by transcranial magnetic stimulation of primary somatosensory cortex.

A number of human and animal studies have reported a differential representation of the frequency of vibrotactile stimuli in the somatosensory cortices: neurons in the primary somatosensory cortex (SI) are predominantly responsive to lower frequencies of tactile vibration, and those in the secondary somatosensory cortex (SII) are predominantly responsive to higher frequencies. We employed transcranial magnetic stimulation (TMS) over SI in human subjects to investigate the extent to which the inactivation of SI disrupted the discrimination of vibrotactile stimulation at frequencies that give rise to the tactile sensations of flutter (30 Hz) and vibration (200 Hz). Frequency discrimination around the 30-Hz standard following application of TMS to SI was reduced in seven of the eight subjects, and around the 200-Hz standard was reduced in all eight subjects. The average change in discrimination following TMS was about 20% for both low and high frequencies of vibrotactile stimulation. These data suggest that disruption of SI: (1) has a direct effect on the discrimination of both low and high frequencies of vibrotactile stimuli, consistent with a serial model of processing, or (2) has a direct effect on low-frequency vibrotactile stimuli and an indirect effect on the processing of high-frequency vibrotactile stimuli by SII via cortico-cortical connections between the two regions.

Branched fibers in dystrophic mdx muscle are associated with a loss of force following lengthening contractions.

We demonstrated that the susceptibility of skeletal muscle to injury from lengthening contractions in the dystrophin-deficient mdx mouse is directly linked with the extent of fiber branching within the muscles and that both parameters increase as the mdx animal ages. We subjected isolated extensor digitorum longus muscles to a lengthening contraction protocol of 15% strain and measured the resulting drop in force production (force deficit). We also examined the morphology of individual muscle fibers. In mdx mice 1-2 mo of age, 17% of muscle fibers were branched, and the force deficit of 7% was not significantly different from that of age-matched littermate controls. In mdx mice 6-7 mo of age, 89% of muscle fibers were branched, and the force deficit of 58% was significantly higher than the 25% force deficit of age-matched littermate controls. These data demonstrated an association between the extent of branching and the greater vulnerability to contraction-induced injury in the older fast-twitch dystrophic muscle. Our findings demonstrate that fiber branching may play a role in the pathogenesis of muscular dystrophy in mdx mice, and this could affect the interpretation of previous studies involving lengthening contractions in this animal.

Synaptic plasticity in the dy2J mouse model of laminin alpha2-deficient congenital muscular dystrophy.

Laminin alpha2-deficient congenital muscular dystrophy is a debilitating disease affecting both muscle and neural tissue as a result of mutations in the LAMA2 gene. It presents at or soon after birth with muscle weakness and is further characterised by clinical central nervous system involvement. Laminin alpha2 is part of the extracellular matrix, linked to the cellular cystoskeleton via dystroglycan which is an integral part of the dystrophin-glycoprotein complex (DGC). We examined both short- and long-term synaptic plasticity in the C57BL6J/dy(2J) mouse, an animal model of laminin alpha2 deficient congenital muscular dystrophy. Using a cerebellar slice preparation, we show that the pre-synaptically mediated paired-pulse facilitation (PPF) was no different between dy(2J) and littermate controls. Approximately half (7/12) the dy(2J) Purkinje cells displayed a blunted LTD compared to littermate controls, and one third (4/12) of dy(2J) Purkinje cells displayed LTP. This study demonstrates that a defective laminin alpha2 causes a disruption in long-term synaptic plasticity at the Purkinje cell-parallel fibre synapse.

Coding of disparity information in extrastriate cortex of the cat.

We have used information theory to analyse the responses of neurons in area 21a of the cat to disparity stimuli. Visual stimuli consisted of drifting sinusoidal gratings presented simultaneously to each eye. The relative spatial phase of the gratings varied between stimulus periods in a pseudo-random sequence of 45 degrees increments that covered the full 360 degrees. The mean information content of the responses of all neurons across all phases was 0.72 bits (+/-0.10, SE, n=29). The information conveyed by each neuron was well correlated with the extent to which the interocular phase difference modulated the response of the cell. However, information content was not simply related to firing rate, as there was usually significant information content in the neuronal responses to phase differences that elicited the minimum firing rate. In general, burst responses (impulse intervals <4 ms) did not convey more information than that conveyed by the total response. The contribution to the cumulative information of the response in successive 100-ms segments decreased over the course of the 1-s stimulus. The ratio of information transmitted at 200 ms to that transmitted over the full second had a median of 0.30 while the ratio of 500 ms to 1 s was 0.68.

Brain function in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the second most commonly occurring genetically inherited disease in humans. It is an X-linked condition that affects approximately one in 3300 live male births. It is caused by the absence or disruption of the protein dystrophin, which is found in a variety of tissues, most notably skeletal muscle and neurones in particular regions of the CNS. Clinically DMD is characterized by a severe pathology of the skeletal musculature that results in the premature death of the individual. An important aspect of DMD that has received less attention is the role played by the absence or disruption of dystrophin on CNS function. In this review we concentrate on insights into this role gained from investigation of boys with DMD and the genetically most relevant animal model of DMD, the dystrophin-deficient mdx mouse. Behavioural studies have shown that DMD boys have a cognitive impairment and a lower IQ (average 85), whilst the mdx mice display an impairment in passive avoidance reflex and in short-term memory. In DMD boys, there is evidence of disordered CNS architecture, abnormalities in dendrites and loss of neurones, all associated with neurones that normally express dystrophin. In the mdx mouse, there have been reports of a 50% decrease in neurone number and neural shrinkage in regions of the cerebral cortex and brainstem. Histological evidence shows that the density of GABA(A) channel clusters is reduced in mdx Purkinje cells and hippocampal CA1 neurones. At the biochemical level, in DMD boys the bioenergetics of the CNS is abnormal and there is an increase in the levels of choline-containing compounds, indicative of CNS pathology. The mdx mice also display abnormal bioenergetics, with an increased level of inorganic phosphate and increased levels of choline-containing compounds. Functionally, DMD boys have EEG abnormalities and there is some preliminary evidence that synaptic function is affected adversely by the absence of dystrophin. Electrophysiological studies of mdx mice have shown that hippocampal neurones have an increased susceptibility to hypoxia. These recent findings on the role of dystrophin in the CNS have implications for the clinical management of boys with DMD.