Chronic Ca2+ imaging of cortical neurons with long-term expression of GCaMP-X

Dynamic Ca2+ signals reflect acute changes in membrane excitability (e.g. sensory response), and also mediate intracellular signaling cascades normally of longer time scales (e.g., Ca2+- dependent neuritogenesis). In both cases, chronic Ca2+ imaging has been often desired, but largely hindered by unexpected cytotoxicity intrinsic to GCaMP, a popular series of genetically-encoded Ca2+ indicators. Here, we demonstrate that the recently developed GCaMP-X outperforms GCaMP in long-term probe expression and/or chronic Ca2+ imaging. GCaMP-X shows much improved compatibility with neurons and thus more reliable than GCaMP as demonstrated in vivo by acute Ca2+ responses to whisker deflection or spontaneous Ca2+ fluctuations over an extended time frame. Chronic Ca2+ imaging data (≥1 month) are acquired from the same set of cultured cortical neurons, unveiling that spontaneous/local Ca2+ activities would progressively develop into autonomous/global Ca2+ oscillations. Besides the morphological indices of neurite length or soma size, the major metrics of oscillatory Ca2+, including rate, amplitude, synchrony among different neurons or organelles have also been examined along with the developmental stages. Both neuritogenesis and Ca2+ signals are dysregulated by GCaMP in virus-infected or transgenic neurons, in direct contrast to GCaMP-X without any noticeable side-effect. Such in vitro data altogether consolidate the unique importance of oscillatory Ca2+ to activity-dependent neuritogenesis, as one major factor responsible for the distinctions between GCaMP vs GCaMP-X in vivo. For the first time with GCaMP-X of long-term expression in neurons, spontaneous and sensory-evoked Ca2+ activities are imaged and evaluated both in vitro and in vivo, providing new opportunities to monitor neural development or other chronic processes concurrently with Ca2+ dynamics.

Difficulties of the tactile sensory system sensory integration of children with autism

Sensory integration represents the organization of the senses for their use. It is a neuro-biological activity that allows the reception and processing of sensory information, which in arrive from the senses in huge quantities into the brain, at any time. The ability of the brain to successfully process tactile information allows the child to feel safe and develop a connection with those around it. An autistic child is not able to register many stimuli from their environment, so insufficient or poor sensory processing can contribute to the image of autism. Children with autism spectrum difficulties have specific difficulties in touch perception. The aim of the study was to examine the prevalence of sensory integration difficulties of the tactile sensory system of children with autism spectrum disorders, and to establish the statistical significance of differences in relation to children without developmental difficulties. The total sample of subjects (N=30) consisted of two subsamples. The first subsample of subjects (N=15) consisted of children with difficulties from the autism spectrum, and the second subsample of subjects (N=15) consisted of children without developmental difficulties. The measurement instrument was the „Questionnaire for testing tactile sensory sensitivity“ with 11 variables and the offered answers of possible sensory response was applied. The Mann-Whitney U test and the Wilcoxon W test at the level of statistical significance of p<0.05 were used to examine the statistical significance of the differences between the subsamples of the subjects. The results of the study showed that 86.67 % of children with autism have difficulties in sensory integration of the tactile sensory system. The hypersensitive type of sensory response has 26.67 %, and the hyposensitive sensory response 20 % of children with autism. 40.00 % of children with autism have a mixed type of tactile sensory. There is a statistically significant difference between children with autism and children without developmental difficulties on 4 variables.

Spatial and Temporal Context Jointly Modulate the Sensory Response within the Ventral Visual Stream

Both spatial and temporal context play an important role in visual perception and behavior. Humans can extract statistical regularities from both forms of context to help process the present and to construct expectations about the future. Numerous studies have found reduced neural responses to expected stimuli compared with unexpected stimuli, for both spatial and temporal regularities. However, it is largely unclear whether and how these forms of context interact. In the current fMRI study, 33 human volunteers were exposed to pairs of object stimuli that could be expected or surprising in terms of their spatial and temporal context. We found reliable independent contributions of both spatial and temporal context in modulating the neural response. Specifically, neural responses to stimuli in expected compared with unexpected contexts were suppressed throughout the ventral visual stream. These results suggest that both spatial and temporal context may aid sensory processing in a similar fashion, providing evidence on how different types of context jointly modulate perceptual processing.

An Artificial Optoelectronic Nociceptor Based on In2S3 Memristor

Nociceptors are an indispensable part of the human nervous system that can sense potential dangers from external environmental stimuli. The biomimetic studies of artificial nociceptors have inspired advanced technology in neuromorphic computing, humanoid robots and artificial visual sensors. In this work, we demonstrate an artificial optoelectronic nociceptor using the memristor of large-area In2S3 thin films. The nociceptor responses not only to electrical stimuli but also illumination of visual light, showing complete nociceptive behaviors of "threshold", "inadaptation", "flabby" and "sensitization". The features of the sensory signal such as responding threshold, relaxation time and sensitivity can be tuned in controllable manner, by the strength and frequency of the external stimuli as well as the biasing of electrostatic gate. Such realization of sensory response to multiple external stimuli in the artificial perceptron demonstrates the feasibility of constructing advanced electronic receptor and artificial human eye.

Children and Young People's Developing Concept of Perceived Value

<p>This thesis examines value perception as part of the decision to purchase, from the perspective of the child consumer. To date no academic research has defined the concept of value perception from a child‟s perspective. On the basis of a two stage qualitative investigation with children aged eight to fourteen years, value for children was found to be an important concept in consumer decisions. Even from the age of eight years, evidence emerged that children were quite „canny‟ in their purchasing. While value was found to be comprised of benefits and costs of purchase for children from this young age, the nature of these factors and the way they contributed to value perception varied considerably as they grew older. Six distinct dimensions emerged from diaries and a series of in-depth interviews with children. The benefits which were identified were functional value, emotional value, social value and curiosity/novelty value while the costs included both price and risk related factors. The way in which the dimensions were considered was found to vary with age, changing from separate consideration of benefits and costs to a more adult like trade-off between the two. The emotional value of products was consistently important for children of all ages, sensory response in particular. Several concepts were found to become increasingly complex. Conceptual understanding of quality emerged as children grew older. Branding was found to be central to children‟s value perceptions despite limited conceptual understanding for very young consumers and the way price was considered changed markedly with age and experience. A conceptual model defining perceived value from a child‟s perspective is detailed and a series of propositions relating important conditions to perceived value are advanced. A discussion of the findings as they relate to the extant literature is provided along with directions for future research, building on the results of this work. Finally, a discussion of the implications of this work for the field of Marketing is presented.</p>

Children and Young People's Developing Concept of Perceived Value

<p>This thesis examines value perception as part of the decision to purchase, from the perspective of the child consumer. To date no academic research has defined the concept of value perception from a child‟s perspective. On the basis of a two stage qualitative investigation with children aged eight to fourteen years, value for children was found to be an important concept in consumer decisions. Even from the age of eight years, evidence emerged that children were quite „canny‟ in their purchasing. While value was found to be comprised of benefits and costs of purchase for children from this young age, the nature of these factors and the way they contributed to value perception varied considerably as they grew older. Six distinct dimensions emerged from diaries and a series of in-depth interviews with children. The benefits which were identified were functional value, emotional value, social value and curiosity/novelty value while the costs included both price and risk related factors. The way in which the dimensions were considered was found to vary with age, changing from separate consideration of benefits and costs to a more adult like trade-off between the two. The emotional value of products was consistently important for children of all ages, sensory response in particular. Several concepts were found to become increasingly complex. Conceptual understanding of quality emerged as children grew older. Branding was found to be central to children‟s value perceptions despite limited conceptual understanding for very young consumers and the way price was considered changed markedly with age and experience. A conceptual model defining perceived value from a child‟s perspective is detailed and a series of propositions relating important conditions to perceived value are advanced. A discussion of the findings as they relate to the extant literature is provided along with directions for future research, building on the results of this work. Finally, a discussion of the implications of this work for the field of Marketing is presented.</p>

Insulin signaling and osmotic stress response regulate arousal and developmental progression of C. elegans at hatching

The progression of animal development from embryonic to juvenile life depends on the coordination of organism-wide responses with environmental conditions. We found that two transcription factors that function in interneuron differentiation in Caenorhabditis elegans, fax-1 and unc-42, are required for arousal and progression from embryogenesis to larval life by potentiating insulin signaling. The combination of mutations in either transcription factor and a mutation in daf-2 insulin receptor results in a novel peri-hatching arrest phenotype; embryos are fully-developed but inactive, often remaining trapped within the eggshell, and fail to initiate pharyngeal pumping. This pathway is opposed by an osmotic sensory response pathway that promotes developmental arrest and a sleep state at the end of embryogenesis in response to elevated salt concentration. The quiescent state induced by loss of insulin signaling or by osmotic stress can be reversed by mutations in genes that are required for sleep. Therefore, countervailing signals regulate late embryonic arousal and developmental progression to larval life, mechanistically linking the two responses. Our findings demonstrate a role for insulin signaling in an arousal circuit, consistent with evidence that insulin-related regulation may function in control of sleep states in many animals. The opposing quiescent arrest state may serve as an adaptive response to the osmotic threat from high salinity environments.

Organic electrolytic photocapacitors for stimulation of the mouse somatosensory cortex

Objective. For decades electrical stimulation has been used in neuroscience to investigate brain networks and been deployed clinically as a mode of therapy. Classically, all methods of electrical stimulation require implanted electrodes to be connected in some manner to an apparatus which provides power for the stimulation itself. Approach. We show the use of novel organic electronic devices, specifically organic electrolytic photocapacitors (OEPCs), which can be activated when illuminated with deep-red wavelengths of light and correspondingly do not require connections with external wires or power supplies when implanted at various depths in vivo. Main results. We stimulated cortical brain tissue of mice with devices implanted subcutaneously, as well as beneath both the skin and skull to demonstrate a wireless stimulation of the whisker motor cortex. Devices induced both a behavior response (whisker movement) and a sensory response in the corresponding sensory cortex. Additionally, we showed that coating OEPCs with a thin layer of a conducting polymer formulation (PEDOT:PSS) significantly increases their charge storage capacity, and can be used to further optimize the applied photoelectrical stimulation. Significance. Overall, this new technology can provide an on-demand electrical stimulation by simply using an OEPC and a deep-red wavelength illumination. Wires and interconnects to provide power to implanted neurostimulation electrodes are often problematic in freely-moving animal research and with implanted electrodes for long-term therapy in patients. Our wireless brain stimulation opens new perspectives for wireless electrical stimulation for applications in fundamental neurostimulation and in chronic therapy.

Engrafted glial progenitor cells yield long-term integration and sensory improvement in aged mice

Aging causes astrocyte morphological degeneration and functional deficiency, which impairs neuronal functions. Until now, whether age-induced neuronal deficiency could be alleviated by engraftment of glial progenitor cell (GPC) derived astrocytes remained unknown. In the current study, GPCs were generated from embryonic cortical neural stem cells in vitro and transplanted into the brains of aged mice. Their integration and intervention effects in the aged brain were examined 12 months after transplantation. Results indicated that these in-vitro-generated GPC-derived astrocytes possessed normal functional properties. After transplantation they could migrate, differentiate, achieve long-term integration, and maintain much younger morphology in the aged brain. Additionally, these GPC-derived astrocytes established endfeet expressing aquaporin-4 (AQP4) and ameliorate AQP4 polarization in the aged neocortex. More importantly, age-dependent sensory response degeneration was reversed by GPC transplantation. This work demonstrates that rejuvenation of the astrocyte niche is a promising treatment to prevent age-induced degradation of neuronal and behavioral functions.

A continuum of intentionality: linking the biogenic and anthropogenic approaches to cognition

Biogenic approaches investigate cognition from the standpoint of evolutionary function, asking what cognition does for a living system and then looking for common principles and exhibitions of cognitive strategies in a vast array of living systems—non-neural to neural. One worry which arises for the biogenic approach is that it is overly permissive in terms of what it construes as cognition. In this paper I critically engage with a recent instance of this way of criticising biogenic approaches in order to clarify their theoretical commitments and prospects. In his critique of the biogenic approach, Fred Adams (Stud Hist Philos Sci 68:20–30, 10.1016/j.shpsa.2017.11.007, 2018) uses the presence of intentional states with conceptual content as a criterion to demarcate cognition-driven behaviour from mere sensory response. In this paper I agree with Adams that intentionality is the mark of the cognitive, but simultaneously reject his overly restrictive conception of intentionality. I argue that understanding intentionality simpliciter as the mark of the mental is compatible with endorsing the biogenic approach. I argue that because cognitive science is not exclusively interested in behaviour driven by intentional states with the kind of content Adams demands, the biogenic approach’s status as an approach to cognition is not called into question. I then go on to propose a novel view of intentionality whereby it is seen to exist along a continuum which increases in the degree of representational complexity: how far into the future representational content can be directed and drive anticipatory behaviour. Understanding intentionality as existing along a continuum allows biogenic approaches and anthropogenic approaches to investigate the same overarching capacity of cognition as expressed in its different forms positioned along the continuum of intentionality. Even if all organisms engage in some behaviour that is driven by weak intentional dynamics, this does not suggest that every behaviour of all organisms is so driven. As such, the worry that the biogenic approach is overly permissive can be avoided.