Biomedical subjects
Publications and source records attributed to Nicholas V Swindale.
A remarkable new technique, two-photon confocal fluorescence microscopy, has revealed an extraordinarily precise organization in the visual cortex. The methodology seems set to become the tool of choice for studying cortical maps.
Multiunit electrodes, in particular tetrodes and polytrodes, are able to isolate action potentials from many neurons simultaneously. However, inaccuracies in the post-acquisition reconstruction of recorded spike waveforms can affect the reliability of spike detection and sorting. Here we show that bandlimited interpolation with sample-and-hold delay correction reduces waveform variability, leading to improved reliability of threshold-based event detection and improved spike sorting accuracy. Interpolation of continuously acquired data is, however, computationally expensive. A cost-benefit analysis was made of varying sampling rates from 12.5 kHz (no interpolation) to 100 kHz (eight times oversampling, with respect to the Nyquist frequency), taking into consideration the final application of the data. For most purposes, including spike sorting, sample rates below 25 kHz with bandlimited interpolation to 50 kHz were ideal, with negligible gains above this rate. A practical benefit, especially for large electrode arrays, is that the bandwidth and storage requirements can be greatly reduced by using data acquisition rates at or slightly above the Nyquist frequency.
We developed a variety of 54-channel high-density silicon electrode arrays (polytrodes) designed to record from large numbers of neurons spanning millimeters of brain. In cat visual cortex, it was possible to make simultaneous recordings from >100 well-isolated neurons. Using standard clustering methods, polytrodes provide a quality of single-unit isolation that surpasses that attainable with tetrodes. Guidelines for successful in vivo recording and precise electrode positioning are described. We also describe a high-bandwidth continuous data-acquisition system designed specifically for polytrodes and an automated impedance meter for testing polytrode site integrity. Despite having smaller interconnect pitches than earlier silicon-based electrodes of this type, these polytrodes have negligible channel crosstalk, comparable reliability, and low site impedances and are capable of making high-fidelity multiunit recordings with minimal tissue damage. The relatively benign nature of planar electrode arrays is evident both histologically and in experiments where the polytrode was repeatedly advanced and retracted hundreds of microns over periods of many hours. It was possible to maintain stable recordings from active neurons adjacent to the polytrode without change in their absolute positions, neurophysiological or receptive field properties.
Optical imaging studies of orientation and direction preference in visual cortex have typically used vector averaging to obtain angle and magnitude maps. This method has shown half-rotation orientation singularities (pinwheels) located within regions of low orientation vector magnitude. Direction preference is generally orthogonal to orientation preference, but often deviates from this, particularly in regions of low direction vector magnitude. Linear regions of rapid change in direction preference terminate in or near orientation singularities. The vector-averaging method is problematic however because it does not clearly disambiguate spatial variation in orientation tuning width from variation in height. It may also wrongly estimate preferred direction in regions where preference is weak. In this paper we analyze optical maps of cat visual cortex by fitting model tuning functions to the responses. This new method reveals features not previously evident. Orientation tuning height and width vary independently across the map: tuning height is always low near singularities, however regions of broad and narrow orientation tuning width can be found in regions of low tuning height, often alternating in a spoke-like fashion around singularities. Orientation and direction preference angles are always closely orthogonal. Reversals in direction preference form lines that originate precisely in orientation singularities.
Despite decades of research, the mechanism by which general anesthetics produce loss of consciousness remains mysterious. A clue may be provided by the evidence that synchronous firing of cortical neurons underlies higher forms of neural processing. In order for these synchrony codes to be precise, transmission time must be independent of path length over all the connected sites between any two cortical areas. Because path lengths vary, developmental mechanisms must compensate for the resulting delay variations. Delay variations could be detected by spike-timing-dependent cues and compensation implemented by systematic changes in axon diameter, myelin thickness, or internodal distance. Anesthetics have been shown to increase conduction velocity in myelinated fibers and may therefore disrupt path-length compensation by changing velocities by different amounts in different types of axon. This simple and testable theory explains why anesthetics interfere selectively with higher cognitive functions but leave those dominated by rate-based firing relatively intact.
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