Further investigation of the spontaneous and evoked activity of the primary neurons of statoreceptors (and other receptors) of the labyrinth of the bullfrog before, during and after an extended period of weightlessness, including alternative intervals of artificial gravity

Vestibular neuron activity was examined by studying nerve stimulation and evoked response. A cooling element, applied to the nerve consisted of a silver hook through which a coolant fluid flowed. Temperature changes were recorded via microtermistors on an eight channel brush recorder, together with response. Diffusion of the cooling effect was measured, recovery time was assessed, and the nerve was then studied hystologically and ultrastructurally. Problems in frog preparation were discussed along with problems in maintaining healthy specimens and bacteria controlled aquaria

Large-scale multielectrode recording and stimulation of neural activity

Large circuits of neurons are employed by the brain to encode and process information. How this encoding and processing is carried out is one of the central questions in neuroscience. Since individual neurons communicate with each other through electrical signals (action potentials), the recording of neural activity with arrays of extracellular electrodes is uniquely suited for the investigation of this question. Such recordings provide the combination of the best spatial (individual neurons) and temporal (individual action-potentials) resolutions compared to other large-scale imaging methods. Electrical stimulation of neural activity in turn has two very important applications: it enhances our understanding of neural circuits by allowing active interactions with them, and it is a basis for a large variety of neural prosthetic devices. Until recently, the state-of-the-art in neural activity recording systems consisted of several dozen electrodes with inter-electrode spacing ranging from tens to hundreds of microns. Using silicon microstrip detector expertise acquired in the field of high-energy physics, we created a unique neural activity readout and stimulation framework that consists of high-density electrode arrays, multi-channel custom-designed integrated circuits, a data acquisition system, and data-processing software. Using this framework we developed a number of neural readout and stimulation systems: (1) a 512-electrode system for recording the simultaneous activity of as many as hundreds of neurons, (2) a 61-electrode system for electrical stimulation and readout of neural activity in retinas and brain-tissue slices, and (3) a system with telemetry capabilities for recording neural activity in the intact brain of awake, naturally behaving animals. We will report on these systems, their various applications to the field of neurobiology, and novel scientific results obtained with some of them. We will also outline future directions

Organic bioelectronic devices to control cell signalling

The nervous system consists of a network of specialized cells that coordinate the actions of the body by transmitting information to and from the brain. The communication between the nerve cells is dependent on the interplay of both electrical and chemical signals. As our understanding of nerve cell signalling increases there is a growing need to develop techniques capable of interfacing with the nervous system. One of the major challenges is to translate between the signal carriers of the nervous system (ions and neurotransmitters) and those of conventional electronics (electrons). Organic conjugated polymers represent a unique class of materials that can utilize both electrons and ions as charge carriers. Taking advantage of this combined feature, we have established a novel communication interface between electronic components and biological systems. The organic bioelectronic devices presented in this thesis are based on the organic electronic ion pump (OEIP) made of the conducting organic polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS). When electronically addressed, electrochemical redox reactions in the polymer translate electronic signals into electrophoretic migration of ions. We show that the device can transport a range of substances involved in nerve cell signaling. These include positively charged ions, neurotransmitters and cholinergic substances. Since the devices are designed to be easily incorporated in conventional microscopy set-ups, we use Ca2+ imaging as readout to monitor cell responses. We demonstrate how electrophoretic delivery of ions and neurotransmitters with precise, spatiotemporal control can be used to modulate intracellular Ca2+ signaling in neuronal cells in the absence of convective disturbances. The electronic control of delivery enables strict control of dynamic parameters, such as amplitude and frequency of Ca2+ responses, and can be used to generate temporal patterns mimicking naturally occurring Ca2+ oscillations. To enable further control and fine-tuning of the ionic signals we developed the electrophoretic chemical transistor, an analogue of the traditional transistor used to amplify and/or switch electronic signals. We thereby take the first step towards integrated chemical circuits. Finally, we demonstrate the use of the OEIP in a new “machine-to-brain” interface. By encapsulating the OEIP we were able to use it in vivo to modulate brainstem responses in guinea pigs. This was the first successful realization of an organic bioelectronic device capable of modulating mammalian sensory function by precise delivery of neurotransmitters. Our findings highlight the potential of communication interfaces based on conjugated polymers in generating complex, high-resolution, signal patterns to control cell physiology. Such devices will have widespread applications across basic research as well as future applicability in medical devices in multiple therapeutic areas

MEDUSA: A Low-Cost, 16-Channel Neuromodulation Platform with Arbitrary Waveform Generation

Neural stimulation systems are used to modulate electrically excitable tissue to interrogate neural circuit function or provide therapeutic benefit. Conventional stimulation systems are expensive and limited in functionality to standard stimulation waveforms, and they are bad for high frequency stimulation. We present MEDUSA, a system that enables new research applications that can leverage multi-channel, arbitrary stimulation waveforms. MEDUSA is low cost and uses commercially available components for widespread adoption. MEDUSA is comprised of a PC interface, an FPGA for precise timing control, and eight bipolar current sources that can each address up to 16 electrodes. The current sources have a resolution of 15.3 nA and can provide ±5 mA with ±5 V compliance. We demonstrate charge-balancing techniques in vitro using a custom microelectrode. An in vivo strength-duration curve for earthworm nerve activation is also constructed using MEDUSA. MEDUSA is a multi-functional neuroscience research tool for electroplating microelectrodes, performing electrical impedance spectroscopy, and examining novel neural stimulation protocols

Implantable CMOS Biomedical Devices

The results of recent research on our implantable CMOS biomedical devices are reviewed. Topics include retinal prosthesis devices and deep-brain implantation devices for small animals. Fundamental device structures and characteristics as well as in vivo experiments are presented

Development and modelling of a versatile active micro-electrode array for high density in-vivo and in-vitro neural signal investigation

The electrophysiological observation of neurological cells has allowed much knowledge to be gathered regarding how living organisms are believed to acquire and process sensation. Although much has been learned about neurons in isolation, there is much more to be discovered in how these neurons communicate within large networks. The challenges of measuring neurological networks at the scale, density and chronic level of non invasiveness required to observe neurological processing and decision making are manifold, however methods have been suggested that have allowed small scale networks to be observed using arrays of micro-fabricated electrodes. These arrays transduce ionic perturbations local to the cell membrane in the extracellular fluid into small electrical signals within the metal that may be measured. A device was designed for optimal electrical matching to the electrode interface and maximal signal preservation of the received extracellular neural signals. Design parameters were developed from electrophysiological computer simulations and experimentally obtained empirical models of the electrode-electrolyte interface. From this information, a novel interface based signal filtering method was developed that enabled high density amplifier interface circuitry to be realised. A novel prototype monolithic active electrode was developed using CMOS microfabrication technology. The device uses the top metallization of a selected process to form the electrode substrate and compact amplification circuitry fabricated directly beneath the electrode to amplify and separate the neural signal from the baseline offsets and noise of the electrode interface. The signal is then buffered for high speed sampling and switched signal routing. Prototype 16 and 256 active electrode array with custom support circuitry is presented at the layout stage for a 20 μm diameter 100 μm pitch electrode array. Each device consumes 26.4 μW of power and contributes 4.509 μV (rms) of noise to the received signal over a controlled bandwidth of 10 Hz - 5 kHz. The research has provided a fundamental insight into the challenges of high density neural network observation, both in the passive and the active manner. The thesis concludes that power consumption is the fundamental limiting factor of high density integrated MEA circuitry; low power dissipation being crucial for the existence of the surface adhered cells under measurement. With transistor sizing, noise and signal slewing each being inversely proportional to the dc supply current and the large power requirements of desirable ancillary circuitry such as analogue-to-digital converters, a situation of compromise is approached that must be carefully considered for specific application design

Investigation of the baroreflex of the rat : steady state and dynamic features

The baroreflex is one of the most important feedback systems in the body to maintain blood pressure variation within the homeostatic range. In this dissertation, the important features of the carotid and aortic baroreflexes have been extensively investigated on ventilated, central nervous system intact, neuromuscular blocked (NMB) rats using different control system and signal processing tools. Studies have demonstrated that sinoaortic denervation (SAD) caused substantial increases in the blood pressure variability. Comparing the pre- and post-SAD blood pressure spectra, there was a significant increase of power in the very low frequency region (0.00195 -0.2 Hz), and a significant decrease of power in the low frequency region (0.2 - 0.6 Hz) after SAD. The dominant power change after SAD was in the very low frequency region of the blood pressure spectra. The carotid and aortic baroreflexes were accessed by volumetric manipulation of the carotid sinus and electrical manipulation of the aortic depressor nerve (ADN) using step and sinusoidal stimulations. Myelinated ADN-A fibers and myelinated + unmyelinated ADN-A+C fibers were accessed separately in the experiments. Results showed that the baroreflex functions as a \u27low-pass\u27 filter, with -3dB cutoff frequency at approximately \u3c0. I Hz. The major working area of the baroreflex system is in the VLF region of the blood pressure spectra. The estimated system transportation lag was 1.07s, which would cause the baroreflex system to oscillate at frequencies around 0.4 Hz. Analyses demonstrated that it is not likely that the baroreflex is activated only occasionally, such as in response to postural shifts, but operates continuously to bring the blood pressure into balance. It is theoretically and experimentally demonstrated that the absolute gain of the open-loop baroreflex system can be predicted by the ratio of the pre-and post- blood pressure amplitude spectra

Design and Optimization of a Low DC Offset in Implanted System for ENG Recording Based on Velocity Selectivity Method

The major target of this paper is the design of advance signal processing system based on minimized length of bits required for digital-to-analogy converter (DAC) for velocity selectivity recording (VSR) approach. The main application of this device is peripheral nerves recording (electroneurogram-ENG) by exploring a spectral analysis for the propagation of neural activities in the velocity domain recording using VSR in implantable application. This research adapted a flexible, compact, andnbspenergynbspefficient dc offset removal circuit. An optimization design has been used based on best possible process involving linearity and area is thus suggested. The system process acquired using this approach were characterized as having a 10-bit signal processing for DAC resolution, with 1.4 mA rms output current, with minimum size around 0.02 mm2nbspof chip area, using FPGA board as prototype design. This paper also explores the design temperature vibration in online recording minimization the output DC offset decrease the heat emission which is significantly for long term implementation applications. This study proposed an analysis circuit configuration demonstrate that this approach could achieve a small DC offset error, with small size required