Heil P.,Leibniz Institute for Neurobiology |
Neubauer H.,Leibniz Institute for Neurobiology |
Irvine D.R.F.,Monash University |
Irvine D.R.F.,Bionics Institute
Journal of Neuroscience | Year: 2011
Acoustic information is conveyed to the brain by the spike patterns in auditory-nerve fibers (ANFs). In mammals, each ANF is excited via a single ribbon synapse in a single inner hair cell (IHC), and the spike patterns therefore also provide valuable information about those intriguing synapses. Herewereexamine and model a key property of ANFs, the dependence of their spike rates on the sound pressure level of acoustic stimuli (rate-level functions). We build upon the seminal model of Sachs and Abbas (1974), which provides good fits to experimental data but has limited utility for defining physiological mechanisms. We present an improved, physiologically plausible model according to which the spike rate follows a Hill equation and spontaneous activity and its experimentally observed tight correlation with ANF sensitivity are emergent properties. We apply it to 156 cat ANF rate-level functions using frequencies where the mechanics are linear and find that a single Hill coefficient of 3 can account for the population of functions. We also demonstrate a tight correspondence between ANF rate-level functions and the Ca 2+ dependence of exocytosis from IHCs, and derive estimates of the effective intracellular Ca 2+ concentrations at the individual active zones of IHCs.Weargue that the Hill coefficient might reflect the intrinsic, biochemical Ca 2+ cooperativity of the Ca 2+ sensor involved in exocytosis from the IHC. The model also links ANF properties with properties of psychophysical absolute thresholds. © 2011 the authors.
Badawy R.A.B.,St Vincents Hospital |
Badawy R.A.B.,University of Melbourne |
Freestone D.R.,University of Melbourne |
Lai A.,Bionics Institute |
And 2 more authors.
Neuroscience | Year: 2012
It has been proposed that the underlying epileptic process is mediated by changes in both excitatory and inhibitory circuits leading to the formation of hyper-excitable seizure networks. In this review we aim to shed light on the many physiological factors that modulate excitability within these networks. These factors have been discussed extensively in many reviews each as a separate entity and cannot be extensively covered in a single manuscript. Thus for the purpose of this work in which we aim to bring those factors together to explain how they interact with epilepsy, we only provide brief descriptions. We present reported evidence supporting the existence of the epileptic brain in several states; interictal, peri-ictal and ictal, each with distinct excitability features. We then provide an overview of how many physiological factors influence the excitatory/inhibitory balance within the interictal state, where the networks are presumed to be functioning normally. We conclude that these changes result in constantly changing states of cortical excitability in patients with epilepsy. © 2012 IBRO.
Zanin M.P.,Bionics Institute |
Pettingill L.N.,Bionics Institute |
Harvey A.R.,University of Western Australia |
Emerich D.F.,Nsgene Inc. |
And 3 more authors.
Journal of Controlled Release | Year: 2012
Cell encapsulation therapies involve the implantation of cells that secrete a therapeutic factor to provide clinical benefits. The transplanted cells are protected from immunorejection via encapsulation in a semipermeable membrane. This treatment strategy was originally investigated as a method for protecting pancreatic islets from immunorejection, thus allowing them to secrete insulin as a chronic treatment for diabetes. Since then a significant body of work has been conducted in developing cell encapsulation therapies to treat a variety of different diseases. Many of these conditions involve neurodegeneration, such as Alzheimer's and Parkinson's disease, as cell encapsulation therapies have proven to be particularly suitable for delivering therapeutics to the central nervous system. This is mainly because they offer chronic delivery of a therapeutic and can be implanted proximal to the affected tissue, bypassing the blood brain barrier, which is impermeable to many agents. Whilst these therapies are not yet widely available in the clinic, promising results have been obtained in several advanced clinical trials and further developmental work is currently underway. This review specifically examines the development of encapsulated cell therapies as treatments for neurological and sensory diseases and evaluates the challenges that are yet to be overcome before they can be made available for clinical use. © 2012 Elsevier B.V.
Lazard D.S.,French Institute of Health and Medical Research |
Lazard D.S.,University Pierre and Marie Curie |
Lazard D.S.,Institute Arthur Vernes |
Innes-Brown H.,Bionics Institute |
And 2 more authors.
Hearing Research | Year: 2014
Not having access to one sense profoundly modifies our interactions with the environment, in turn producing changes in brain organization. Deafness and its rehabilitation by cochlear implantation offer a unique model of brain adaptation during sensory deprivation and recovery. Functional imaging allows the study of brain plasticity as a function of the times of deafness and implantation. Even long after the end of the sensitive period for auditory brain physiological maturation, some plasticity may be observed. In this way the mature brain that becomes deaf after language acquisition can adapt to its modified sensory inputs. Oral communication difficulties induced by post-lingual deafness shape cortical reorganization of brain networks already specialized for processing oral language. Left hemisphere language specialization tends to be more preserved than functions of the right hemisphere. We hypothesize that the right hemisphere offers cognitive resources re-purposed to palliate difficulties in left hemisphere speech processing due to sensory and auditory memory degradation. If cochlear implantation is considered, this reorganization during deafness may influence speech understanding outcomes positively or negatively. Understanding brain plasticity during post-lingual deafness should thus inform the development of cognitive rehabilitation, which promotes positive reorganization of the brain networks that process oral language before surgery. This article is part of a Special Issue entitled
Fallon J.B.,Bionics Institute |
Fallon J.B.,University of Melbourne |
Shepherd R.K.,Bionics Institute |
Shepherd R.K.,University of Melbourne |
Irvine D.R.F.,Bionics Institute
European Journal of Neuroscience | Year: 2014
Extended periods of deafness have profound effects on central auditory system function and organization. Neonatal deafening results in loss of the normal cochleotopic organization of the primary auditory cortex (AI), but environmentally-derived intracochlear electrical stimulation, via a cochlear implant, initiated shortly after deafening, can prevent this loss. We investigated whether such stimulation initiated after an extended period of deafness can restore cochleotopy. In two groups of neonatally-deafened cats, a multi-channel intracochlear electrode array was implanted at 8 weeks of age. One group received only minimal stimulation, associated with brief recordings at 4-6-week intervals, over the following 6 months to check the efficacy of the implant. In the other group, this 6-month period was followed by 6 months of near-continuous intracochlear electrical stimulation from a modified clinical cochlear implant system. We recorded multi-unit clusters in the auditory cortex and used two different methods to define the region of interest in the putative AI. There was no evidence of cochleotopy in any of the minimally stimulated animals, confirming our earlier finding. In three of six chronically stimulated cats there was clear evidence of AI cochleotopy, and in a fourth cat in which the majority of penetrations were in the anterior auditory field there was clear evidence of cochleotopy in that field. The finding that chronic intracochlear electrical stimulation after an extended period of deafness is able to restore cochleotopy in some (but not all) cases has implications for the performance of patients implanted after an extended period of deafness. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Peterson A.J.,Leibniz Institute for Neurobiology |
Irvine D.R.F.,Monash University |
Irvine D.R.F.,Bionics Institute |
Heil P.,Leibniz Institute for Neurobiology |
Heil P.,Center for Behavioral Brain science
Journal of Neuroscience | Year: 2014
In mammalian auditory systems, the spiking characteristics of each primary afferent (type I auditory-nerve fiber; ANF) are mainly determined by a single ribbon synapse in a single receptor cell (inner hair cell; IHC).ANFspike trains therefore provide a window into the operation of these synapses and cells. It was demonstrated previously (Heil et al., 2007) that the distribution of interspike intervals (ISIs) of cat ANFs during spontaneous activity can be modeled as resulting from refractoriness operating on a non-Poisson stochastic point process of excitation (transmitter release events from the IHC). Here,weinvestigate nonrenewal properties of these cat-ANF spontaneous spike trains, manifest as negative serial ISI correlations and reduced spike-count variability over short timescales.Apreviously discussed excitatory process, the constrained failure of events from a homogeneous Poisson point process, can account for these properties, but does not offer a parsimonious explanation for certain trends in the data. We then investigate a three-parameter model of vesicle-pool depletion and replenishment and find that it accounts for all experimental observations, including the ISI distributions, with only the release probability varying between spike trains. The maximum number of units (single vesicles or groups of simultaneously released vesicles) in the readily releasable pool and their replenishment time constant can be assumed to be constant (∼4 and 13.5 ms, respectively). We suggest that the organization of the IHC ribbon synapses not only enables sustained release of neurotransmitter but also imposes temporal regularity on the release process, particularly when operating at high rates. © 2014 the authors.
Richardson R.T.,Bionics Institute |
Atkinson P.J.,Stanford University
Expert Opinion on Biological Therapy | Year: 2015
Introduction: The sensory epithelium of the cochlea is a complex structure containing hair cells, supporting cells and auditory nerve endings, all of which degenerate after hearing loss in mammals. Biological approaches are being considered to preserve and restore the sensory epithelium after hearing loss. Of particular note is the ectopic expression of the Atoh1 gene, which has been shown to convert residual supporting cells into hair cells with restoration of function in some cases.Areas covered: In this review, hair cell development, spontaneous regeneration and hair cell regeneration mediated by Atoh1 gene therapy in the cochlea are discussed.Expert opinion: Gene therapy can be safely delivered locally to the inner ear and can be targeted to the sensory epithelium of the cochlea. Expression of the Atoh1 gene in supporting cells results in their transformation into cells with the appearance and function of immature hair cells but with the resulting loss of the original supporting cell. While the feasibility of Atoh1 gene therapy in the cochlea is largely dependent on the severity of the hearing loss, hearing restoration can be achieved in some situations. With further advances in Atoh1 gene therapy, hearing loss may not be as permanent as once thought. © 2014 Informa UK, Ltd.
Tan J.,Bionics Institute |
Tan J.,University of Melbourne |
Wang Y.,University of Melbourne |
Yip X.,Bionics Institute |
And 4 more authors.
Advanced Materials | Year: 2012
Neurotrophin-BDNF can be effectively encapsulated in nanoporous poly(L-glutamic acid) particles prepared via mesoporous silica templating. The loaded BDNF can be released in a sustained manner with retained biological activity. Animal experiments demonstrate the released BDNF can efficiently rescue the auditory neurons (as indicated by the arrows) in the cochlea of guinea pigs with sensorineural hearing loss. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Francart T.,Catholic University of Leuven |
Francart T.,Bionics Institute |
McDermott H.J.,Bionics Institute |
McDermott H.J.,University of Melbourne
Ear and Hearing | Year: 2013
The addition of acoustic stimulation to electric stimulation via a cochlear implant has been shown to be advantageous for speech perception in noise, sound quality, music perception, and sound source localization. However, the signal processing and fitting procedures of current cochlear implants and hearing aids were developed independently, precluding several potential advantages of bimodal stimulation, such as improved sound source localization and binaural unmasking of speech in noise. While there is a large and increasing population of implantees who use a hearing aid, there are currently no generally accepted fitting methods for this configuration. It is not practical to fit current commercial devices to achieve optimal binaural loudness balance or optimal binaural cue transmission for arbitrary signals and levels. There are several promising experimental signal processing systems specifically designed for bimodal stimulation. In this article, basic psychophysical studies with electric acoustic stimulation are reviewed, along with the current state of the art in fitting, and experimental signal processing techniques for electric acoustic stimulation. Copyright © 2013 by Lippincott Williams & Wilkins.
Villalobos J.,Bionics Institute
Investigative ophthalmology & visual science | Year: 2013
The safety of chronic implantation of a retinal prosthesis in the suprachoroidal space has not been established. This study aimed to determine the safety of a wide-field suprachoroidal electrode array following chronic implantation using histopathologic techniques and electroretinography. A platinum electrode array in a wide silicone substrate was implanted unilaterally in the suprachoroidal space in adult cats (n = 7). The lead and connector were tunneled out of the orbit and positioned subcutaneously. Postsurgical recovery was assessed using fundus photography and electroretinography (ERG). Following 3 months of passive implantation, the animals were terminated and the eyes assessed for the pathologic response to implantation. The implant was mechanically stable in the suprachoroidal space during the course of the study. The implanted eye showed a transient increase in ERG response amplitude at 2 weeks, which returned to normal by 3 months. Pigmentary changes were observed at the distal end of the implant, near the optic disc. Histopathologic assessment revealed a largely intact retina and a thin fibrous capsule around the suprachoroidal implant cavity. The foreign body response was minimal, with sporadic presence of macrophages and no active inflammation. All implanted eyes were negative for bacterial or fungal infections. A midgrade granuloma and thick fibrous buildup surrounded the extraocular cable. Scleral closure was maintained in six of seven eyes. There were no staphylomas or choroidal incarceration. A wide-field retinal prosthesis was stable and well tolerated during long-term suprachoroidal implantation in a cat model. The surgical approach was reproducible and overall safe.