scholarly journals Robot-Embodied Neuronal Networks as an Interactive Model of Learning

2017 ◽  
Vol 11 (1) ◽  
pp. 39-47
Author(s):  
Abraham M Shultz ◽  
Sangmook Lee ◽  
Mary Guaraldi ◽  
Thomas B. Shea ◽  
Holly A. Yanco

Background and Objective:The reductionist approach of neuronal cell culture has been useful for analyses of synaptic signaling. Murine cortical neurons in culture spontaneously form anex vivonetwork capable of transmitting complex signals, and have been useful for analyses of several fundamental aspects of neuronal development hitherto difficult to clarifyin situ. However, these networks lack the ability to receive and respond to sensory input from the environment as do neuronsin vivo. Establishment of these networks in culture chambers containing multi-electrode arrays allows recording of synaptic activity as well as stimulation.Method:This article describes the embodiment ofex vivoneuronal networks neurons in a closed-loop cybernetic system, consisting of digitized video signals as sensory input and a robot arm as motor output.Results:In this system, the neuronal network essentially functions as a simple central nervous system. This embodied network displays the ability to track a target in a naturalistic environment. These findings underscore thatex vivoneuronal networks can respond to sensory input and direct motor output.Conclusion:These analyses may contribute to optimization of neuronal-computer interfaces for perceptive and locomotive prosthetic applications.Ex vivonetworks display critical alterations in signal patterns following treatment with subcytotoxic concentrations of amyloid-beta. Future studies including comparison of tracking accuracy of embodied networks prepared from mice harboring key mutations with those from normal mice, accompanied with exposure to Abeta and/or other neurotoxins, may provide a useful model system for monitoring subtle impairment of neuronal function as well as normal and abnormal development.

2018 ◽  
Vol 12 (1) ◽  
pp. 64-68
Author(s):  
Thomas B. Shea ◽  
Ruth Remington

Objective:Audio files of spontaneous signal streams generated byex vivoneuronal networks cultured on multi-electrode arrays generated an oscillating sine wave with an inherent musical quality. This was not anticipated considering that synaptic signals are “all - or – none”, and therefore digital, events.Methods:These findings may provide insight into why music can be perceived as pleasurable and invoke a calm mood despite that music is ultimately perceived and stored as a series of digital signals; it is speculated that music may reinforce and/or enhance this spontaneous digital stream.Results and Conclusion:These findings also support the relationship between music and mathematics.


2021 ◽  
Vol 15 (1) ◽  
pp. 3-15
Author(s):  
Thomas B. Shea

The responsiveness of the human nervous system ranges from the basic sensory interpretation and motor regulation to so-called higher-order functions such as emotion and consciousness. Aspects of higher-order functions are displayed by other mammals and birds. In efforts to understand how neuronal interaction can generate such a diverse functionality, murine embryonic cortical neurons were cultured on Petri dishes containing multi-electrode arrays that allowed recording and stimulation of neuronal activity. Despite the lack of major architectural features that govern nervous system development in situ, this overview of multiple studies demonstrated that these 2-dimensional ex vivo neuronal networks nevertheless recapitulate multiple key aspects of nervous system development and activity in situ, including density-dependent, the spontaneous establishment of a functional network that displayed complex signaling patterns, and responsiveness to environmental stimulation including generation of appropriate motor output and long-term potentiation. These findings underscore that the basic interplay of excitatory and inhibitory neuronal activity underlies all aspects of nervous system functionality. This reductionist system may be useful for further examination of neuronal function under developmental, homeostatic, and neurodegenerative conditions.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Federico Tinarelli ◽  
Elena Ivanova ◽  
Ilaria Colombi ◽  
Erica Barini ◽  
Edoardo Balzani ◽  
...  

Abstract Background DNA methylation has emerged as an important epigenetic regulator of brain processes, including circadian rhythms. However, how DNA methylation intervenes between environmental signals, such as light entrainment, and the transcriptional and translational molecular mechanisms of the cellular clock is currently unknown. Here, we studied the after-hours mice, which have a point mutation in the Fbxl3 gene and a lengthened circadian period. Methods In this study, we used a combination of in vivo, ex vivo and in vitro approaches. We measured retinal responses in Afh animals and we have run reduced representation bisulphite sequencing (RRBS), pyrosequencing and gene expression analysis in a variety of brain tissues ex vivo. In vitro, we used primary neuronal cultures combined to micro electrode array (MEA) technology and gene expression. Results We observed functional impairments in mutant neuronal networks, and a reduction in the retinal responses to light-dependent stimuli. We detected abnormalities in the expression of photoreceptive melanopsin (OPN4). Furthermore, we identified alterations in the DNA methylation pathways throughout the retinohypothalamic tract terminals and links between the transcription factor Rev-Erbα and Fbxl3. Conclusions The results of this study, primarily represent a contribution towards an understanding of electrophysiological and molecular phenotypic responses to external stimuli in the Afh model. Moreover, as DNA methylation has recently emerged as a new regulator of neuronal networks with important consequences for circadian behaviour, we discuss the impact of the Afh mutation on the epigenetic landscape of circadian biology.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Thu T. Duong ◽  
James Lim ◽  
Vidyullatha Vasireddy ◽  
Tyler Papp ◽  
Hung Nguyen ◽  
...  

Recombinant adeno-associated virus (rAAV), produced from a nonpathogenic parvovirus, has become an increasing popular vector for gene therapy applications in human clinical trials. However, transduction and transgene expression of rAAVs can differ acrossin vitroand ex vivo cellular transduction strategies. This study compared 11 rAAV serotypes, carrying one reporter transgene cassette containing a cytomegalovirus immediate-early enhancer (eCMV) and chicken beta actin (CBA) promoter driving the expression of an enhanced green-fluorescent protein (eGFP) gene, which was transduced into four different cell types: human iPSC, iPSC-derived RPE, iPSC-derived cortical, and dissociated embryonic day 18 rat cortical neurons. Each cell type was exposed to three multiplicity of infections (MOI: 1E4, 1E5, and 1E6 vg/cell). After 24, 48, 72, and 96 h posttransduction, GFP-expressing cells were examined and compared across dosage, time, and cell type. Retinal pigmented epithelium showed highest AAV-eGFP expression and iPSC cortical the lowest. At an MOI of 1E6 vg/cell, all serotypes show measurable levels of AAV-eGFP expression; moreover, AAV7m8 and AAV6 perform best across MOI and cell type. We conclude that serotype tropism is not only capsid dependent but also cell type plays a significant role in transgene expression dynamics.


2001 ◽  
Vol 435 (3) ◽  
pp. 276-282 ◽  
Author(s):  
Richard E. Coggeshall ◽  
Helena A. Lekan ◽  
Fletcher A. White ◽  
Clifford J. Woolf

Author(s):  
Vesna Lazarevic ◽  
Yunting Yang ◽  
Ivana Flais ◽  
Per Svenningsson

AbstractKetamine produces a rapid antidepressant response in patients with major depressive disorder (MDD), but the underlying mechanisms appear multifaceted. One hypothesis, proposes that by antagonizing NMDA receptors on GABAergic interneurons, ketamine disinhibits afferens to glutamatergic principal neurons and increases extracellular glutamate levels. However, ketamine seems also to reduce rapid glutamate release at some synapses. Therefore, clinical studies in MDD patients have stressed the need to identify mechanisms whereby ketamine decreases presynaptic activity and glutamate release. In the present study, the effect of ketamine and its antidepressant metabolite, (2R,6R)-HNK, on neuronally derived glutamate release was examined in rodents. We used FAST methodology to measure depolarization-evoked extracellular glutamate levels in vivo in freely moving or anesthetized animals, synaptosomes to detect synaptic recycling ex vivo and primary cortical neurons to perform functional imaging and to examine intracellular signaling in vitro. In all these versatile approaches, ketamine and (2R,6R)-HNK reduced glutamate release in a manner which could be blocked by AMPA receptor antagonism. Antagonism of adenosine A1 receptors, which are almost exclusively expressed at nerve terminals, also counteracted ketamine’s effect on glutamate release and presynaptic activity. Signal transduction studies in primary neuronal cultures demonstrated that ketamine reduced P-T286-CamKII and P-S9-Synapsin, which correlated with decreased synaptic vesicle recycling. Moreover, systemic administration of A1R antagonist counteracted the antidepressant-like actions of ketamine and (2R,6R)-HNK in the forced swim test. To conclude, by studying neuronally released glutamate, we identified a novel retrograde adenosinergic feedback mechanism that mediate inhibitory actions of ketamine on glutamate release that may contribute to its rapid antidepressant action.


Leonardo ◽  
2009 ◽  
Vol 42 (5) ◽  
pp. 439-442 ◽  
Author(s):  
Eduardo R. Miranda ◽  
John Matthias

Music neurotechnology is a new research area emerging at the crossroads of neurobiology, engineering sciences and music. Examples of ongoing research into this new area include the development of brain-computer interfaces to control music systems and systems for automatic classification of sounds informed by the neurobiology of the human auditory apparatus. The authors introduce neurogranular sampling, a new sound synthesis technique based on spiking neuronal networks (SNN). They have implemented a neurogranular sampler using the SNN model developed by Izhikevich, which reproduces the spiking and bursting behavior of known types of cortical neurons. The neurogranular sampler works by taking short segments (or sound grains) from sound files and triggering them when any of the neurons fire.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Zhanyang Yu ◽  
Ning Liu ◽  
Eng H Lo ◽  
Thomas J McCarthy ◽  
Xiaoying Wang

Background: Low level light (or laser) therapy (LLLT) has been studied and practiced for promoting wound healing, reducing pain, inflammation, and ischemic tissue damage. Recently, a series of experimental and clinical investigations have suggested that LLLT may be a novel therapy against hypoxic/ischemic brain damage. A clinical trial of LLLT therapy for ischemic stroke is now on going. However, the molecular mechanism of LLLT-conferred neuroprotection remains poorly defined. In this study, we tested our hypothesis that LLLT may attenuate impairments of mitochondrial function induced by hypoxic/ischemic insults in primary cultured mouse cortical neurons. Method: At day 9 of culture, primary neurons were subjected to 4 hr OGD followed by reoxygenation. One 810-nm LLLT treatment was applied for 2 minutes at 2 hr after reoxygenation. Neurotoxicity was measured after 20 hr after reoxygenation by LDH release assay. We also measured MTT reduction and mitochondria membrane potential (MMP) at 2 hr after LLLT treatment as markers of mitochondrial function. Results: The neurotoxicity study showed that 4 hr OGD plus 20 hr reoxygenation caused 33.8± 3.4% neuronal cell death, while LLLT treatment significantly reduced the neuronal death rate to 23.6± 2.9% (30.2% reduction, n=6, p smaller than 0.05). Mitochondrial functional assays showed OGD decreased MTT reduction to 75.9± 2.68%, but LLLT treatment significantly rescued MTT reduction to 87.6±4.55% (15.4% improvement, n=6, p smaller than 0.05). Furthermore, after OGD, MMP was reduced to 48.9±4.39%, while LLLT treatment significantly ameliorated this reduction to 89.6± 13.9% (83% improvement, n=4, p smaller than 0.05) compared to normoxic controls. Conclusion: The present study suggests that LLLT treatment is protective against OGD-induced neurotoxicity of primary neurons and that this protection may be conferred through preservation or rescue of mitochondrial function.


2021 ◽  
Vol 11 ◽  
Author(s):  
Thomas R. Zentall

The hypothesis proposed by Macphail (1987) is that differences in intelligent behavior thought to distinguish different species were likely attributed to differences in the context of the tasks being used. Once one corrects for differences in sensory input, motor output, and incentive, it is likely that all vertebrate animals have comparable intellectual abilities. In the present article I suggest a number of tests of this hypothesis with pigeons. In each case, the evidence suggests that either there is evidence for the cognitive behavior, or the pigeons suffer from biases similar to those of humans. Thus, Macphail’s hypothesis offers a challenge to researchers to find the appropriate conditions to bring out in the animal the cognitive ability being tested.


Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 647-658
Author(s):  
N. Maeda ◽  
M. Noda

6B4 proteoglycan/phosphacan is one of the major phosphate-buffered saline-soluble chondroitin sulfate proteoglycans of the brain. Recently, this molecule has been demonstrated to be an extracellular variant of the proteoglycan-type protein tyrosine phosphatase, PTPzeta (RPTPbeta). The influence of the 6B4 proteoglycan, adsorbed onto the substratum, on cell adhesion and neurite outgrowth was studied using dissociated neurons from the cerebral cortex and thalamus. 6B4 proteoglycan adsorbed onto plastic tissue culture dishes did not support neuronal cell adhesion, but rather exerted repulsive effects on cortical and thalamic neurons. When neurons were densely seeded on patterned substrata consisting of a grid-like structure of alternating poly-L-lysine and 6B4 proteoglycan-coated poly-L-lysine domains, they were concentrated on the poly-L-lysine domains. However, 6B4 proteoglycan did not retard the differentiation of neurons but rather promoted neurite outgrowth and development of the dendrites of cortical neurons, when neurons were sparsely seeded on poly-L-lysine-conditioned coverslips continuously coated with 6B4 proteoglycan. This effect of 6B4 proteoglycan on the neurite extension of cortical neurons was apparent even on coverslips co-coated with fibronectin or tenascin. By contrast, the neurite extension of thalamic neurons was not modified by 6B4 proteoglycan. Chondroitinase ABC or keratanase digestion of 6B4 proteoglycan did not affect its neurite outgrowth promoting activity, but a polyclonal antibody against 6B4 proteoglycan completely suppressed this activity, suggesting that a protein moiety is responsible for the activity. 6B4 proteoglycan transiently promoted tyrosine phosphorylation of an 85x10(3) Mr protein in the cortical neurons, which correlated with the induction of neurite outgrowth. These results suggest that 6B4 proteoglycan/phosphacan modulates morphogenesis and differentiation of neurons dependent on its spatiotemporal distribution and the cell types in the brain.


Sign in / Sign up

Export Citation Format

Share Document