Pierre Wijdenes | University of Calgary (original) (raw)

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Papers by Pierre Wijdenes

Our inability to accurately monitor individual neurons and their synaptic activity precludes fund... more Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro-and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively. Here, we present the next generation of planar microelectrode arrays with " nano-edges " that enable long-term (≥1 month) and high fidelity recordings at a resolution 15 times higher than traditional planar electrodes. This novel technology enables better understanding of brain function and offers a tremendous opportunity towards the development of future bionic hybrids and drug discovery devices. Various neuronal activity recording and stimulating devices enable cellular exploration 1–3 using micro-and nano-devices 4. A multitude of penetrating and non-penetrating nanopillar electrodes 5–7 , carbon nanotube electrodes 8 , mushroom-shaped protruding microelectrodes 9 , planar microelectrode arrays (MEAs) etc. have been used to record neuronal activities. Among such devices are three-dimensional and planar microelectrodes, each with their respective advantages and disadvantages. Whereas, the three-dimensional electrodes tend to allow for high fidelity recordings they only do so over a short time period (hours to days). On the other hand, the planar microelectrodes permit longer-term recordings (weeks to months), albeit at the expense of low signal resolution. Ideally, combining both advantages would permit long-term and high-resolution recordings, which, in turn, could offer new opportunities to monitor and record subtle aspects of brain activity. Inspired by the structural attributes of a synaptic cleft, our team reports here on the next generation of planar microelectrode arrays with nano-edges offering high fidelity recordings over long time periods. Design and analysis Inspired by the morphology of a synaptic cleft, whereby both pre-and postsynaptic structures are juxtaposed and semi-encapsulated, we developed microelectrodes mimicking a synapse morphology as well as neuronal juxtapo-sition with their adjacent cells. Specifically, microelectrodes that " bio-mimic " the postsynaptic cleft were designed to exhibit 'nano-edges' that provide a tighter physical and dielectrical seal between the device and the neuron. This structural geometry was also anticipated to prevent the leakage of current into the surrounding extracellular milieu, thus preserving and augmenting the functional integrity of chemical and electrical neuronal signal processing (Fig. 1a,b). We named these types of microelectrodes as " nano-edge microelectrodes ". Gold planar microelectrodes were fabricated using a standard photolithography technique and lift-off process. Electrode sizes, and distances between them, were adjusted according to our experimental needs by modifying the photomask designs, allowing us to keep the design relatively simple, economical and scalable. Once the planar microelectrodes were fabricated, the nano-edge was added using a custom photolithography process. Following the fabrication, we characterized and validated the morphological attributes of the microelectrodes with atomic force microscopy (Fig. 1c) and were able to qualitatively confirm the presence of the nano-edges (Fig. 1d).

Journal of neuroscience methods, Jan 3, 2015

Background Microelectrode arrays have been used successfully for neuronal stimulation both in viv... more Background Microelectrode arrays have been used successfully for neuronal stimulation both in vivo and in vitro. However, in most instances currents required to activate the neurons have been in un-physiological ranges resulting in neuronal damage and cell death. There is a need to develop electrodes which require less stimulation current for neuronal activation with physiologically relevant efficacy and frequencies. New method The objective of the present study was to examine and compare the stimulation efficiency of different electrode geometries at the resolution of a single neuron. We hypothesized that increasing the electrode perimeter will increase the maximum current density at the edges and enhance stimulation efficiency. To test this postulate, the neuronal stimulation efficacy of common circular electrodes (smallest perimeter) was compared with sinusoidal (medium perimeter), and spiral (largest perimeter with internal boundaries) electrodes. We explored and compared using ...

Scientific reports, 2015

Highly coordinated and coincidental patterns of activity-dependent mechanisms ("fire togethe... more Highly coordinated and coincidental patterns of activity-dependent mechanisms ("fire together wire together") are thought to serve as inductive signals during synaptogenesis, enabling neuronal pairing between specific sub-sets of excitatory partners. However, neither the nature of activity triggers, nor the "activity signature" of long-term neuronal firing in developing/regenerating neurons have yet been fully defined. Using a highly tractable model system comprising of identified cholinergic neurons from Lymnaea, we have discovered that intrinsic trophic factors present in the Lymnaea brain-conditioned medium (CM) act as a natural trigger for activity patterns in post- but not the presynaptic neuron. Using microelectrode array recordings, we demonstrate that trophic factors trigger stereotypical activity patterns that include changes in frequency, activity and variance. These parameters were reliable indicators of whether a neuron expressed functional excitatory...

Journal of neuroscience methods, Jan 3, 2015

Background Microelectrode arrays have been used successfully for neuronal stimulation both in viv... more Background Microelectrode arrays have been used successfully for neuronal stimulation both in vivo and in vitro. However, in most instances currents required to activate the neurons have been in un-physiological ranges resulting in neuronal damage and cell death. There is a need to develop electrodes which require less stimulation current for neuronal activation with physiologically relevant efficacy and frequencies. New method The objective of the present study was to examine and compare the stimulation efficiency of different electrode geometries at the resolution of a single neuron. We hypothesized that increasing the electrode perimeter will increase the maximum current density at the edges and enhance stimulation efficiency. To test this postulate, the neuronal stimulation efficacy of common circular electrodes (smallest perimeter) was compared with sinusoidal (medium perimeter), and spiral (largest perimeter with internal boundaries) electrodes. We explored and compared using ...

Our inability to accurately monitor individual neurons and their synaptic activity precludes fund... more Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro-and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively. Here, we present the next generation of planar microelectrode arrays with " nano-edges " that enable long-term (≥1 month) and high fidelity recordings at a resolution 15 times higher than traditional planar electrodes. This novel technology enables better understanding of brain function and offers a tremendous opportunity towards the development of future bionic hybrids and drug discovery devices. Various neuronal activity recording and stimulating devices enable cellular exploration 1–3 using micro-and nano-devices 4. A multitude of penetrating and non-penetrating nanopillar electrodes 5–7 , carbon nanotube electrodes 8 , mushroom-shaped protruding microelectrodes 9 , planar microelectrode arrays (MEAs) etc. have been used to record neuronal activities. Among such devices are three-dimensional and planar microelectrodes, each with their respective advantages and disadvantages. Whereas, the three-dimensional electrodes tend to allow for high fidelity recordings they only do so over a short time period (hours to days). On the other hand, the planar microelectrodes permit longer-term recordings (weeks to months), albeit at the expense of low signal resolution. Ideally, combining both advantages would permit long-term and high-resolution recordings, which, in turn, could offer new opportunities to monitor and record subtle aspects of brain activity. Inspired by the structural attributes of a synaptic cleft, our team reports here on the next generation of planar microelectrode arrays with nano-edges offering high fidelity recordings over long time periods. Design and analysis Inspired by the morphology of a synaptic cleft, whereby both pre-and postsynaptic structures are juxtaposed and semi-encapsulated, we developed microelectrodes mimicking a synapse morphology as well as neuronal juxtapo-sition with their adjacent cells. Specifically, microelectrodes that " bio-mimic " the postsynaptic cleft were designed to exhibit 'nano-edges' that provide a tighter physical and dielectrical seal between the device and the neuron. This structural geometry was also anticipated to prevent the leakage of current into the surrounding extracellular milieu, thus preserving and augmenting the functional integrity of chemical and electrical neuronal signal processing (Fig. 1a,b). We named these types of microelectrodes as " nano-edge microelectrodes ". Gold planar microelectrodes were fabricated using a standard photolithography technique and lift-off process. Electrode sizes, and distances between them, were adjusted according to our experimental needs by modifying the photomask designs, allowing us to keep the design relatively simple, economical and scalable. Once the planar microelectrodes were fabricated, the nano-edge was added using a custom photolithography process. Following the fabrication, we characterized and validated the morphological attributes of the microelectrodes with atomic force microscopy (Fig. 1c) and were able to qualitatively confirm the presence of the nano-edges (Fig. 1d).

Journal of neuroscience methods, Jan 3, 2015

Background Microelectrode arrays have been used successfully for neuronal stimulation both in viv... more Background Microelectrode arrays have been used successfully for neuronal stimulation both in vivo and in vitro. However, in most instances currents required to activate the neurons have been in un-physiological ranges resulting in neuronal damage and cell death. There is a need to develop electrodes which require less stimulation current for neuronal activation with physiologically relevant efficacy and frequencies. New method The objective of the present study was to examine and compare the stimulation efficiency of different electrode geometries at the resolution of a single neuron. We hypothesized that increasing the electrode perimeter will increase the maximum current density at the edges and enhance stimulation efficiency. To test this postulate, the neuronal stimulation efficacy of common circular electrodes (smallest perimeter) was compared with sinusoidal (medium perimeter), and spiral (largest perimeter with internal boundaries) electrodes. We explored and compared using ...

Scientific reports, 2015

Highly coordinated and coincidental patterns of activity-dependent mechanisms ("fire togethe... more Highly coordinated and coincidental patterns of activity-dependent mechanisms ("fire together wire together") are thought to serve as inductive signals during synaptogenesis, enabling neuronal pairing between specific sub-sets of excitatory partners. However, neither the nature of activity triggers, nor the "activity signature" of long-term neuronal firing in developing/regenerating neurons have yet been fully defined. Using a highly tractable model system comprising of identified cholinergic neurons from Lymnaea, we have discovered that intrinsic trophic factors present in the Lymnaea brain-conditioned medium (CM) act as a natural trigger for activity patterns in post- but not the presynaptic neuron. Using microelectrode array recordings, we demonstrate that trophic factors trigger stereotypical activity patterns that include changes in frequency, activity and variance. These parameters were reliable indicators of whether a neuron expressed functional excitatory...

Journal of neuroscience methods, Jan 3, 2015

Background Microelectrode arrays have been used successfully for neuronal stimulation both in viv... more Background Microelectrode arrays have been used successfully for neuronal stimulation both in vivo and in vitro. However, in most instances currents required to activate the neurons have been in un-physiological ranges resulting in neuronal damage and cell death. There is a need to develop electrodes which require less stimulation current for neuronal activation with physiologically relevant efficacy and frequencies. New method The objective of the present study was to examine and compare the stimulation efficiency of different electrode geometries at the resolution of a single neuron. We hypothesized that increasing the electrode perimeter will increase the maximum current density at the edges and enhance stimulation efficiency. To test this postulate, the neuronal stimulation efficacy of common circular electrodes (smallest perimeter) was compared with sinusoidal (medium perimeter), and spiral (largest perimeter with internal boundaries) electrodes. We explored and compared using ...