Hamish Meffin

Spike-timing-dependent plasticity: the relationship to rate-based learning for models with weight dynamics determined by a stable fixed point

Experimental evidence indicates that synaptic modification depends on the timing relationship between the presynaptic inputs and the output spikes that they generate. In this letter, results are presented for models of spike-timing-dependent plasticity (STDP) whose weight dynamics is determined by a stable fixed point. Four classes of STDP are identified on the basis of the time extent of their input-output interactions. The effect on the potentiation of synapses with different rates of input is investigated to elucidate the relationship of STDP with classical studies of long-term potentiation and depression and rate-based Hebbian learning. The selective potentiation of higher-rate synaptic inputs is found only for models where the time extent of the input-output interactions is input restricted (i.e., restricted to time domains delimited by adjacent synaptic inputs) and that have a time-asymmetric learning window with a longer time constant for depression than for potentiation. The analysis provides an account of learning dynamics determined by an input-selective stable fixed point. The effect of suppressive interspike interactions on STDP is also analyzed and shown to modify the synaptic dynamics.

Electrical stimulation of retinal ganglion cells with diamond and the development of an all diamond retinal prosthesis

Electronic retinal implants for the blind are already a market reality. A world wide effort is underway to find the technology that offers the best combination of performance and safety for potential patients. Our approach is to construct an epi-retinally targeted device entirely encapsulated in diamond to maximise longevity and biocompatibility. The stimulating array of our device comprises a monolith of electrically insulating diamond with thousands of hermetic, microscale nitrogen doped ultra-nanocrystalline diamond (N-UNCD) feedthroughs. Here we seek to establish whether the conducting diamond feedthroughs of the array can be used as stimulating electrodes without further modification with a more traditional neural stimulation material. Efficacious stimulation of retinal ganglion cells was established using single N-UNCD microelectrodes in contact with perfused, explanted, rat retina. Evoked rat retinal ganglion cell action potentials were recorded by patch clamp recording from single ganglion cells, adjacent to the N-UNCD stimulating electrode. Separately, excellent electrochemical stability of N-UNCD was established by prolonged pulsing in phosphate buffered saline at increasing charge density up to the measured charge injection limit for the material.

Ultra-nanocrystalline diamond electrodes: optimization towards neural stimulation applications

Diamond is well known to possess many favourable qualities for implantation into living tissue including biocompatibility, biostability, and for some applications hardness. However, conducting diamond has not, to date, been exploited in neural stimulation electrodes due to very low electrochemical double layer capacitance values that have been previously reported. Here we present electrochemical characterization of ultra-nanocrystalline diamond electrodes grown in the presence of nitrogen (N-UNCD) that exhibit charge injection capacity values as high as 163 µC cm(-2) indicating that N-UNCD is a viable material for microelectrode fabrication. Furthermore, we show that the maximum charge injection of N-UNCD can be increased by tailoring growth conditions and by subsequent electrochemical activation. For applications requiring yet higher charge injection, we show that N-UNCD electrodes can be readily metalized with platinum or iridium, further increasing charge injection capacity. Using such materials an implantable neural stimulation device fabricated from a single piece of bio-permanent material becomes feasible. This has significant advantages in terms of the physical stability and hermeticity of a long-term bionic implant.

Study of neuronal gain in a conductance-based leaky integrate-and-fire neuron model with balanced excitatory and inhibitory synaptic input

Abstract.Neurons receive a continual stream of excitatory and inhibitory synaptic inputs. A conductance-based neuron model is used to investigate how the balanced component of this input modulates the amplitude of neuronal responses. The output spiking rate is well described by a formula involving three parameters: the mean μ and variance σ of the membrane potential and the effective membrane time constant τQ. This expression shows that, for sufficiently small τQ, the level of balanced excitatory-inhibitory input has a nonlinear modulatory effect on the neuronal gain.

An Analytical Model for the 'Large, Fluctuating Synaptic Conductance State' Typical of Neocortical Neurons In Vivo

A model of in vivo-like neocortical activity is studied analytically in relation to experimental data and other models in order to understand the essential mechanisms underlying such activity. The model consists of a network of sparsely connected excitatory and inhibitory integrate-and-fire (IF) neurons with conductance-based synapses. It is shown that the model produces values for five quantities characterizing in vivo activity that are in agreement with both experimental ranges and a computer-simulated Hodgkin-Huxley model adapted from the literature (Destexhe et al. (2001) Neurosci. 107(1): 13–24). The analytical model builds on a study by Brunel (2000) (J. Comput. Neurosci. 8: 183–208), which used IF neurons with current-based synapses, and therefore does not account for the full range of experimental data. The present results suggest that the essential mechanism required to explain a range of data on in vivo neocortical activity is the conductance-based synapse and that the particular model of spike initiation used is not crucial. Thus the IF model with conductance-based synapses may provide a basis for the analytical study of the ‘large, fluctuating synaptic conductance state’ typical of neocortical neurons in vivo.

Modeling extracellular electrical stimulation: I. Derivation and interpretation of neurite equations

Neuroprosthetic devices, such as cochlear and retinal implants, work by directly stimulating neurons with extracellular electrodes. This is commonly modeled using the cable equation with an applied extracellular voltage. In this paper a framework for modeling extracellular electrical stimulation is presented. To this end, a cylindrical neurite with confined extracellular space in the subthreshold regime is modeled in three-dimensional space. Through cylindrical harmonic expansion of Laplaces equation, we derive the spatio-temporal equations governing different modes of stimulation, referred to as longitudinal and transverse modes, under types of boundary conditions. The longitudinal mode is described by the well-known cable equation, however, the transverse modes are described by a novel ordinary differential equation. For the longitudinal mode, we find that different electrotonic length constants apply under the two different boundary conditions. Equations connecting current density to voltage boundary conditions are derived that are used to calculate the trans-impedance of the neurite-plus-thin-extracellular-sheath. A detailed explanation on depolarization mechanisms and the dominant current pathway under different modes of stimulation is provided. The analytic results derived here enable the estimation of a neurites membrane potential under extracellular stimulation, hence bypassing the heavy computational cost of using numerical methods.

Modelling intrinsic electrophysiological properties of ON and OFF retinal ganglion cells

ON and OFF retinal ganglion cells (RGCs) display differences in their intrinsic electrophysiology: OFF cells maintain spontaneous activity in the absence of any input, exhibit subthreshold membrane potential oscillations, rebound excitation and burst firing; ON cells require excitatory input to drive their activity and display none of the aforementioned phenomena. The goal of this study was to identify and characterize ionic currents that explain these intrinsic electrophysiological differences between ON and OFF RGCs. A mathematical model of the electrophysiological properties of ON and OFF RGCs was constructed and validated using published patch-clamp data from isolated intact mouse retina. The model incorporates three ionic currents hypothesized to play a role in generating behaviors that are different between ON and OFF RGCs. These currents are persistent Na + , INaP, hyperpolarization-activated, Ih, and low voltage activated Ca2 + , IT, currents. Using computer simulations of Hodgkin-Huxley type neuron with a single compartment model we found two distinct sets of INaP, Ih, IT conductances that correspond to ON and OFF RGCs populations. Simulations indicated that special properties of IT explain the differences in intrinsic electrophysiology between ON and OFF RGCs examined here. The modelling shows that the maximum conductance of IT is higher in OFF than in ON cells, in agreement with recent experimental data.

In vivo biocompatibility of boron doped and nitrogen included conductive‐diamond for use in medical implants

Recently, there has been interest in investigating diamond as a material for use in biomedical implants. Diamond can be rendered electrically conducting by doping with boron or nitrogen. This has led to inclusion of boron doped and nitrogen included diamond elements as electrodes and/or feedthroughs for medical implants. As these conductive device elements are not encapsulated, there is a need to establish their clinical safety for use in implants. This article compares the biocompatibility of electrically conducting boron doped diamond (BDD) and nitrogen included diamond films and electrically insulating poly crystalline diamond films against a silicone negative control and a BDD sample treated with stannous octoate as a positive control. Samples were surgically implanted into the back muscle of a guinea pig for a period of 4-15 weeks, excised and the implant site sectioned and submitted for histological analysis. All forms of diamond exhibited a similar or lower thickness of fibrotic tissue encapsulating compared to the silicone negative control samples. All forms of diamond exhibited similar or lower levels of acute, chronic inflammatory, and foreign body responses compared to the silicone negative control indicating that the materials are well tolerated in vivo.

A Complete 256-Electrode Retinal Prosthesis Chip

This paper presents a complete 256-electrode retinal prosthesis chip, which is small and ready for packaging and implantation. It contains 256 separate programmable drivers dedicated to 256 electrodes for flexible stimulation. A 4-wire interface is employed for power and data transmission between the chip and a driving unit. Power and forward data are recovered from a 600 kHz differential signal, while backward data are sent at 100 kbps rate simultaneously. The stimulator possesses many stimulation features, supporting various stimulation strategies. Many safety features are included such as real-time monitoring of voltage compliance and temperature, electrode self-locking in the event of out-of-compliance, and ESD protection circuit at every electrode. The chip is fabricated in a 65 nm CMOS process. The electrode driver pitch is 150 μm, and total chip area is 8 mm 2 . The chip has been extensively tested and all the requirements have been successfully verified. The measured DC current error for single driver stimulation without electrode shorting is 20 nA. The average power consumption per electrode with typical stimulus pulse parameters and full-scale output current is 129 μW, inclusive of all standby power. The chip overall power efficiency is 70% with 23 mW of power delivered to load.

Heating of the Eye by a Retinal Prosthesis: Modeling, Cadaver and In Vivo Study

In order to develop retinal implants with a large number of electrodes, it is necessary to ensure that they do not cause damage to the neural tissue by the heat that the electrical circuits generate. Knowledge of the amount of power that induces thermal damage will assist in development of power budgets for implants, which has a significant effect upon the design of the prostheses circuitry. In this study, temperatures were measured at multiple locations on the retina while the retina was heated in cadaver and in vivo preparations using a variety of prosthesis implantation sites. A finite element thermal model of the cat eye was also created and validated by the cadaver and in vivo tests, allowing for a much larger spectrum of thermal influences to be evaluated without additional animal experimentation. To ensure that retinal tissue temperatures are not increased by more than 2 °C, a 5 mm × 5 mm, suprachoroidally implanted heating element must not dissipate more than 135 mW (5.4 mW/mm2).