<p>In recent years, large-scale brain recordings in nonhuman primates have been a driving force for both fundamental neuroscience and the field of brain-machine interfaces (BMIs). This required monkey implants connected to external amplifiers and computers with ever increasing number of cables. As shown with our recent demonstration of 2,000 neurons recorded in one monkey, a tethered recording system begins to get bulky and complex, particularly for our BMI and neurophysiological research. To address this problem, we developed a multichannel wireless recording framework. The system was been tested in freely moving rhesus monkey by integrating wireless neural recordings with external computers performing BMI decoding, behavioral manipulanda and optical tracking. This technology can be applied to primate behavior research and, in the near future, wireless, fully implantable human neuroprosthetics, which is of great significance to those suffering from locomotor deficiencies, such as those brought on by spinal cord injury and stroke. Aided with these advances, I was able to study monkeys in unrestrained locomotion while their cortical activity was continuously monitored. I also explored unrestrained behaviors and how they showed distinct transitions in neural dynamics as monkeys engaged in different behavioral activities or learned new motor skills, such as bipedal walking. I was able to decode them many of these behavioral states from cortical activity with neural classifiers. Lastly, monkeys were able to perform BMI tasks continuously for many hours, allowing us to prove the relevance of unrestrained noise in BMI performance. Lastly, I present my role in developing two brain actuated movement platforms, a robotic exoskeleton under the guise of the WalkAgain project, and a microelectrode BMI enabled wheelchair. This body of work should assist those on the path to the next generation of clinical neuroprostheses and neural communication systems.</p> / Dissertation

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Der primäre somatosensorische Kortex (S1) besteht aus sechs Schichten (L1L6).Die koordinierte Aktivität dieser sechs Schichten kortikaler Neurone ist entscheidend für die sensorische Wahrnehmung und die Steuerung willkürlichen Verhaltens. Es ist jedoch noch wenig über die synaptischen Mechanismen bekannt, die die Verarbeitung zwischen den kortikalen Schichten bei sich aktiv verhaltenden Tieren bestimmen. Ich habe einfache und doppelte in vivoGanzzellableitungen im VorderpfotenAreal von S1 in der Maus gemacht, und gezeigt, dass Pyramidalzellen in L2/3 und L5 während einer Bewegung der Vorderpfote Unterschiede in ihren intrinsischen Eigenschaften und der Dynamik ihrer Membranpotenziale zeigen. Doppelableitungen haben gezeigt, dass sensorisch und motorisch ausgelöste synaptische Eingänge zwischen den Zellschichten weitgehend korreliert waren, niederfrequente unterschwellige Potenzialschwankungen und spontane Aktionspotenziale jedoch einen schichtspezifischen Zeitverlauf zeigten. Auf einer längeren Zeitskala beobachteten wir, dass spontane Bewegungen der Vorderpfote eine Dekorrelation unterschwelliger Aktivität zwischen den Schichten auslösten. Des Weiteren zeigten L5Pyramidalzellen durch ihre Aktivität sensorisch ausgelöste und spontane Bewegungen der Vorderpfote stärker an, als L2/3Neurone. Insgesamt deuten meine Daten darauf hin, dass Unterschiede zwischen den Zellschichten beim Timing von Aktionspotenzialen, bei der unterschwelligen Synchronisierung und bei den mittleren Feuerraten sowohl von der Quelle des zu Grunde liegenden synaptischen Eingangs als auch vom resultierenden Verhalten abhängen. Außerdem konnte ich zeigen, dass Neurone im VorderpfotenAreal von S1 auf leichte Kältereizung der Vorderpfote antworten, und dass diese Antwort vom Ionenkanal transient receptor potential cation channel subfamily M member 8 (TRPM8) in primären sensorischen afferenten Neuronen vermittelt wird. / The primary somatosensory cortex (SI) is composed of six layers (L1L6). The coordination of neural activities across six layers of cortical neurons is essential for reliable sensory perception and the control of voluntary behavior. However, the synaptic neural mechanisms governing translaminar cortical processing in behaving animals are still unknown. I made in vivo single and dual whole cell recordings in mouse forepaw SI, my work revealed that L2/3 and L5 pyramidal neurons have distinct intrinsic properties and membrane potential dynamics during forepaw behavior. Dual recordings showed that sensory and movement evoked synaptic inputs were closely correlated across layers, but low frequency subthreshold fluctuations and spontaneous action potentials exhibited a laminar specific temporal profile. At longer time scales, my data showed that spontaneous forepaw movement evoked a decorrelation of subthreshold activity across layers. Furthermore, L5 pyramidal neurons signaled sensory evoked and spontaneous forepaw movements more strangely than L2/3 neurons. Overall, my work suggests that laminar differences in the timing of action potential firing, subthreshold synchrony and mean firing rates are dependent both on the origin of the underlying synaptic input and the behavioral outcome of the event. In addition, I identified that forepaw SI neurons respond to mild cooling stimulation of the forepaw and that this response is mediated by the Transient receptor potential cation channel subfamily M member 8 (TRPM8) in primary sensory afferent neurons.