Analysis and learning of dynamic binary neural networks which can generate variable phenomena

研究成果の概要 (和文) : 2層の動的バイナリーニューラルネット(DBNN)に2値周期軌道(BPO)を銘記する学習法を構築した。同手法をパワーエレクトロニクスの基本回路の制御信号に対応する教師信号BPOに適用し、手法の有効性を確認した。また、デジタルリターンマップを用いてDBNNの動作を視覚化する方法も提案し、学習過程の把握に有効であることを明らかにした。DBNNにBPOが銘記できた場合に、結合行列をスパース化すると、それに落ち込む初期値の数が増え、安定性が強化される場合のあることを示した。いくつかの基本的な例題教師信号によって、そのスパース化の有効性を確認した。研究成果の概要 (英文) : We have constructed a learning method to store one desired binary periodic orbit (BPO) into to the dynamic binary neural networks is presented. Applying the method to teacher signal BPOs that correspond to control signals of basic switching power converters, the efficiency of the method is confirmed. Introducing a digital return map, the dynamics of the DBNN is visualized and analyzed.In the case where a desired BPO can be stored into a DBNN, we have clarified that　stability of the stored BPO can be reinforced (the number of initial points falling into the BPO is increased) by sparsifying connection matrix. In several basic examples of teacher signals, the efficiency of the sparsification is confirmed

Feed-Forward Propagation of Temporal and Rate Information between Cortical Populations during Coherent Activation in Engineered In Vitro Networks.

Transient propagation of information across neuronal assembles is thought to underlie many cognitive processes. However, the nature of the neural code that is embedded within these transmissions remains uncertain. Much of our understanding of how information is transmitted among these assemblies has been derived from computational models. While these models have been instrumental in understanding these processes they often make simplifying assumptions about the biophysical properties of neurons that may influence the nature and properties expressed. To address this issue we created an in vitro analog of a feed-forward network composed of two small populations (also referred to as assemblies or layers) of living dissociated rat cortical neurons. The populations were separated by, and communicated through, a microelectromechanical systems (MEMS) device containing a strip of microscale tunnels. Delayed culturing of one population in the first layer followed by the second a few days later induced the unidirectional growth of axons through the microtunnels resulting in a primarily feed-forward communication between these two small neural populations. In this study we systematically manipulated the number of tunnels that connected each layer and hence, the number of axons providing communication between those populations. We then assess the effect of reducing the number of tunnels has upon the properties of between-layer communication capacity and fidelity of neural transmission among spike trains transmitted across and within layers. We show evidence based on Victor-Purpura's and van Rossum's spike train similarity metrics supporting the presence of both rate and temporal information embedded within these transmissions whose fidelity increased during communication both between and within layers when the number of tunnels are increased. We also provide evidence reinforcing the role of synchronized activity upon transmission fidelity during the spontaneous synchronized network burst events that propagated between layers and highlight the potential applications of these MEMs devices as a tool for further investigation of structure and functional dynamics among neural populations

Chemical and Physical Determinants of Cell Migration

The phenomenon of directed cell motion in response to external directional cues has drawn significant interest for more than a century, with the first recorded observations of bacterial chemotaxis at the end of the 19th century. Furthermore, movies generated by David Rogers while at Vanderbilt University of a peripheral blood neutrophil tracking a bacterium are a staple of any college biology class to demonstrate the phenomenon of eukaryotic chemotaxis. In just the last decade, our understanding of the biochemical mechanisms underlying the process of directed eukaryotic cell migration. As a result, several generalized processes have been identified, connecting multiple phenomena from cancer metastasis to axon guidance. Making further sense of the complex biochemical pathways requires both quantitative mathematical models and fine control over the external cellular environment. To this end, microfluidics has proven extremely useful, allowing for precise quantification of both the external environment and the cellular response

Telemetry Controlled Brain Machine Interface To Train Cortical Circuits

The goal of this dissertation is to document functional reorganization in rat primary somatosensory (SI) cortex. This work proposes to strengthen the interhemispheric connection between homotopic sites in forelimb barrel cortex (FBC) through intracortical microstimulation (ICMS) and induce functional reorganization whereby neurons in the FBC respond to new input from the ipsilateral forelimb. Furthermore, a wireless microstimulation and recording device was developed for producing enhancement and functional reorganization of cortical circuits in FBC. The goal of Experiment One was to test the hypothesis that layer V neurons projected to homotopic sites in contralateral layer V FBC. Retrograde or anterograde neuronal tracer injections were made to characterize the distribution of callosal projecting neurons in contralateral SI that terminate in layer VFBC and where layer V callosal projecting neurons terminate in contralateral SI. The results showed a differential pattern of interhemispheric connectivity between homotopic forelimb representations in layer V FBC. The goal of Experiment Two was to test the hypothesis that ICMS enhances the interhemispheric pathway and leads to functional reorganization. ICMS was delivered in vivo to the interhemispheric pathway between homotopic layer V barrel cortices and multiunit recordings were made to assess changes in firing rate. The results showed ICMS strengthens interhemispheric connectivity and leads to functional reorganization in rat FBC. The goal of Experiment Three was to develop an interactive telemetry-based neural interface device for the controlled delivery of ICMS and recording response activity in rodent. The device successfully delivered microstimulation to a single electrode in SIand recorded evoked responses from a separate electrode in contralateral SI. Its performance was shown to be comparable to commercial stimulating and recording systems. This system serves as a prototype of a wearable compact device. The data suggest that neurons in rat FBC can be induced to respond to new input from the ipsilateral forelimb by enhancing the interhemispheric pathway with ICMS. An interactive system for the controlled delivery of telemetry-based microstimulation and real-time recordings has been demonstrated in vivo. These studies provide the framework for subsequent studies of interhemispheric pathway enhancement and functional reorganization in freely moving rats

Disruption of Lateral Olivocochlear Neurons via a Dopaminergic Neurotoxin Depresses Sound-Evoked Auditory Nerve Activity

We applied the dopaminergic (DA) neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the guinea pig cochlear perilymph. Immunolabeling of lateral olivocochlear (LOC) neurons using antibodies against synaptophysin was reduced after the MPTP treatment. In contrast, labeling of the medial olivocochlear innervation remained intact. As after brainstem lesions of the lateral superior olive (LSO), the site of origin of the LOC neurons, the main effect of disrupting LOC innervation of the cochlea via MPTP was a depression of the amplitude of the compound action potential (CAP). CAP amplitude depression was similar to that produced by LSO lesions. Latency of the N1 component of the CAP, and distortion product otoacoustic emission amplitude and adaptation were unchanged by the MPTP treatment. This technique for selectively lesioning descending LOC efferents provides a new opportunity for examining LOC modulation of afferent activity and behavioral measures of perception.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41386/1/10162_2004_Article_2429.pd

Ageing and gastrointestinal sensory function: Altered colonic mechanosensory and chemosensory function in the aged mouse

Ageing has a profound effect upon gastrointestinal function through mechanisms that are poorly understood. Here we investigated the effect of age upon gastrointestinal sensory signalling pathways in order to address the mechanisms underlying these changes. In vitro mouse colonic and jejunal preparations with attached splanchnic and mesenteric nerves were used to study mechanosensory and chemosensory afferent function in 3-, 12- and 24-month-old C57BL/6 animals. Quantitative RT-PCR was used to investigate mRNA expression in colonic tissue and dorsal root ganglion (DRG) cells isolated from 3- and 24-month animals, and immunohistochemistry was used to quantify the number of 5-HT-expressing enterochromaffin (EC) cells. Colonic and jejunal afferent mechanosensory function was attenuated with age and these effects appeared earlier in the colon compared to the jejunum. Colonic age-related loss of mechanosensory function was more pronounced in high-threshold afferents compared to low-threshold afferents. Chemosensory function was attenuated in the 24-month colon, affecting TRPV1 and serotonergic signalling pathways. High-threshold mechanosensory afferent fibres and small-diameter DRG neurons possessed lower functional TRPV1 receptor responses, which occurred without a change in TRPV1 mRNA expression. Serotonergic signalling was attenuated at 24 months, but TPH1 and TPH2 mRNA expression was elevated in colonic tissue. In conclusion, we saw an age-associated decrease in afferent mechanosensitivity in the mouse colon affecting HT units. These units have the capacity to sensitise in response to injurious events, and their loss in ageing may predispose the elderly to lower awareness of GI injury or disease

Development of a Low Profile, Endoscopic Implant for Long Term Brain Imaging

The increased public awareness of concussion and traumatic brain injury has motivated continued research into the brain, its functions, and especially its response to injury, with a focus on improving the brain’s repair capabilities. However, due to the critical nature of the tissue, it is currently difficult for researchers to acquire high resolution images below the cortex without sacrificing a lab animal. Sacrificing an animal greatly reduces the amount of data that can be obtained from it, making longitudinal studies unappealing or unfeasible because a large number of animals is needed to obtain useful data over multiple time points. Additionally, inter-animal variance can further obfuscate results. The gradient index (GRIN) lens is a form of micro-endoscope that can penetrate the cortex to obtain high resolution, in vivo images when used with a multiphoton microscope system. The lens is implanted through the skull and into the brain, providing a column of material that refracts and refocuses the laser beam, unlike the natural tissue, which scatters light. This dissertation describes the development of a low profile GRIN lens implant system suitable for longitudinal imaging, as well as the co-development of a restraint system to accommodate the new implant on a microscope stage. The imaging protocol is detailed, and images acquired over three months are shown. The developed device drastically reduced the size of implant both above the skull and within the brain tissue compared to previously reported GRIN lenses, while still obtaining the expected high resolution images. This research also found that labelled axons in transgenic mice appear in unique, recognizable patterns which remain consistent over months of imaging, meaning future studies may use the axons themselves as landmarks. An experimental design for analyzing traumatic brain injury is also developed, which could incorporate a future implant

Assessing neuronal coherence with single-unit, multi-unit and local field potentials

None of the material has been published or is under consideration for pub lication elsewhere. 1 A b stra c t T he p u rp o se of th is stu d y w as to o b tain a b e tte r u n d e r stan d in g of neu ro n al responses to co rrelated in p u t, in p a rtic u lar focussing on th e asp ect of sy nchronizatio n of n eu ro n al activity. T h e first aim w as to o b tain an an aly tical expression for th e coherence betw een th e o u tp u t spike tra in an d co rre la te d in p u t and for th e coherence betw een o u tp u t spike tra in s of neu ro n s w ith co rrelated in p u t. For Poisson neurons, we could derive th a t th e p eak of th e coherence betw een th e cor re la te d in p u t and m u lti-u n it activ ity increases p ro p o rtio n ally w ith th e square ro o t of th e n u m b er of neurons in th e m u lti u n it recording. T h e coherence betw een tw o typical m u lti-u n it record in gs (2 to 10 single-units) w ith p a rtia lly co rrelated in p u t increases p ro p o rtio n ally w ith th e n u m b er of u n its in th e m u lti-u n it recordings. T he second aim of th is stu d y w as to investigate to w h at e x ten t th e am p litu d e an d signal-to-noise ra tio of th e coherence betw een in p u t and o u tp u t varied for single versus m u lti-u n it activ ity and how th e y are affected by th e d u ra tio n of th e recording. T h e sam e pro b lem w as a d dressed for th e coherence betw een tw o single-unit spike series an d betw een tw o m u lti-u n it spike series. T he an aly tical re su lts for th e Poisson n eu ro n and nu m erical sim ulations for th e co n d u ctan ce-b ased leaky in teg rate-an d -fire n eu ro n an d for th e co n d u ctan ce-b ased H odgkin-H uxley n eu ro n show th a t th e ex p e c ta tio n value of th e coherence fun ctio n does no t increase for a longer d u ra tio n of th e recording. T h e only effect of a longer d u ra tio n of th e spike record in g is a re d u ctio n of th e noise in th e coherence function. T h e resu lts of an aly tical derivation s and c o m p u ter sim ulations for m odel neurons show th a t th e coher ence for m u lti-u n it activ ity is larg er th a n th a t for single-unit activity. T his is in agreem ent w ith th e resu lts of ex p erim en tal d a ta o b tain ed from m onkey visual co rtex (V 4). Finally, we show th a t m u lti-ta p e r tech niqu es g reatly c o n trib u te to a m ore a c cu ra te estim a te of th e coherence by redu cin g th e bias and variance in th e coherence estim ate.

Network mechanisms underlying stable motor actions

While we can learn to produce stereotyped movements and maintain this ability for years, it is unclear how populations of individual neurons change their firing properties to coordinate these skills. This has been difficult to address because there is a lack of tools that can monitor populations of single neurons in freely behaving animals for the durations required to remark on their tuning. This thesis is divided into two main directions- device engineering and systems neuroscience. The first section describes the development of an electrode array comprised of tiny self-splaying carbon fibers that are small and flexible enough to avoid the immune response that typically limits electrophysiological recordings. I also describe the refinement of a head-mounted miniature microscope system, optimized for multi-month monitoring of cells expressing genetically encoded calcium indicators in freely behaving animals. In the second section, these tools are used to answer basic systems neuroscience questions in an animal with one of the most stable, complex learned behaviors in the animal kingdom: songbirds. This section explores the functional organization and long-term network stability of HVC, the songbird premotor cortical microcircuit that controls song. Our results reveal that neural activity in HVC is correlated with a length scale of 100um. At this mesocopic scale, basal-ganglia projecting excitatory neurons, on average, fire at a specific phase of a local 30Hz network rhythm. These results show that premotor cortical activity is inhomogeneous in time and space, and that a mesoscopic dynamical pattern underlies the generation of the neural sequences controlling song. At this mesoscopic level, neural coding is stable for weeks and months. These ensemble patterns persist after peripheral nerve damage, revealing that sensory-motor correspondence is not required to maintain the stability of the underlying neural ensemble. However, closer examination of individual excitatory neurons reveals that the participation of cells can change over the timescale of days- with particularly large shifts occurring over instances of sleep. Our findings suggest that fine-scale drift of projection neurons, stabilized by mesoscopic level dynamics dominated by inhibition, forms the mechanistic basis of memory maintenance and and motor stability