Mapping the spatiotemporal dynamics of calcium signaling in cellular neural networks using optical flow

An optical flow gradient algorithm was applied to spontaneously forming net- works of neurons and glia in culture imaged by fluorescence optical microscopy in order to map functional calcium signaling with single pixel resolution. Optical flow estimates the direction and speed of motion of objects in an image between subsequent frames in a recorded digital sequence of images (i.e. a movie). Computed vector field outputs by the algorithm were able to track the spatiotemporal dynamics of calcium signaling pat- terns. We begin by briefly reviewing the mathematics of the optical flow algorithm, and then describe how to solve for the displacement vectors and how to measure their reliability. We then compare computed flow vectors with manually estimated vectors for the progression of a calcium signal recorded from representative astrocyte cultures. Finally, we applied the algorithm to preparations of primary astrocytes and hippocampal neurons and to the rMC-1 Muller glial cell line in order to illustrate the capability of the algorithm for capturing different types of spatiotemporal calcium activity. We discuss the imaging requirements, parameter selection and threshold selection for reliable measurements, and offer perspectives on uses of the vector data.Comment: 23 pages, 5 figures. Peer reviewed accepted version in press in Annals of Biomedical Engineerin

Age-Specific Prevalence of Hoarding and Obsessive Compulsive Disorder: A Population-Based Study

Objective: Little is known about the age-specific prevalence of hoarding and obsessive compulsive symptoms (OCS), particularly in older age groups. The objectives of this study were to estimate the age-specific prevalence, severity, and relationships between hoarding and OCS in males and females using a large population-based sample. Methods: We assessed the age-specific prevalence rates of hoarding disorder (HD) and OC disorder (OCD) in males and females (at various age ranges between 15 and 97 years) from the Netherlands Twins Register (N = 15,194). Provisional HD and OCD diagnoses were made according to Diagnostic and Statistical Manual of Mental Health Disorders, 5th Edition, criteria using self-report measures. We also assessed hoarding and OCS severity in the various age groups and explored specific hoarding and OCS patterns (e.g., difficulty discarding, excessive acquisition, clutter, checking, washing, perfectionism, and obsessions) with age. Results: Prevalence of provisional HD diagnoses (2.12%) increased linearly by 20% with every 5 years of age (z = 13.8, p <0.0001) and did not differ between males and females. Provisional OCD diagnoses were most common in younger individuals and in individuals over age 65. Co-occurring OCD increased hoarding symptom severity (coefficient: 4.5; SE: 0.2; 95% CI: 4.1-4.9; t = 22.0, p <0.0001). Difficulty discarding for HD and checking behaviors for OCD appeared to drive most increases in these diagnoses in older ages. Conclusion: Increased prevalence and severity of HD with age appears to be primarily driven by difficulties with discarding. Increases in OCD prevalence with older age were unexpected and of potential clinical relevance

Age-Specific Prevalence of Hoarding and Obsessive Compulsive Disorder: A Population-Based Study

OBJECTIVE: Little is known about the age-specific prevalence of hoarding and obsessive compulsive symptoms (OCS), particularly in older age groups. The objectives of this study were to estimate the age-specific prevalence, severity, and relationships between hoarding and OCS in males and females using a large population-based sample. METHODS: We assessed the age-specific prevalence rates of hoarding disorder (HD) and OC disorder (OCD) in males and females (at various age ranges between 15 and 97 years) from the Netherlands Twins Register (N = 15,194). Provisional HD and OCD diagnoses were made according to Diagnostic and Statistical Manual of Mental Health Disorders, 5th Edition, criteria using self-report measures. We also assessed hoarding and OCS severity in the various age groups and explored specific hoarding and OCS patterns (e.g., difficulty discarding, excessive acquisition, clutter, checking, washing, perfectionism, and obsessions) with age. RESULTS: Prevalence of provisional HD diagnoses (2.12%) increased linearly by 20% with every 5 years of age (z = 13.8, p < 0.0001) and did not differ between males and females. Provisional OCD diagnoses were most common in younger individuals and in individuals over age 65. Co-occurring OCD increased hoarding symptom severity (coefficient: 4.5; SE: 0.2; 95% CI: 4.1-4.9; t = 22.0, p < 0.0001). Difficulty discarding for HD and checking behaviors for OCD appeared to drive most increases in these diagnoses in older ages. CONCLUSION: Increased prevalence and severity of HD with age appears to be primarily driven by difficulties with discarding. Increases in OCD prevalence with older age were unexpected and of potential clinical relevance

Deficits in physiological and self-conscious emotional response to errors in hoarding disorder.

Hoarding disorder (HD) has been hypothesized to arise from deficits in error monitoring and abnormalities in emotional processing, but the relationship between error monitoring and emotional processing has not been examined. We examined measures of self-report, as well as behavioral, physiological, and facial responses to errors during a Stop-Change Task. 25 participants with HD and 32 healthy controls (HC) were recruited. Participants reported on number of errors committed and pre/post emotional response to errors. Skin conductance response (SCR) during correct and error commission trials was examined. Facial expression during task performance was coded for self-conscious and negative emotions. HD and HC participants had significantly different error rates but comparable error correction and post-error slowing. SCR was significantly lower for HD during error commission than for HC. During error trials, HD participants showed a significant deficit in displays of self-conscious emotions compared to HC. Self-reported emotions were increased in HD, with more negative and self-conscious emotion reported than was reported for HC participants. These findings suggest that hypoactive emotional responding at a physiological level may play a role in how errors are processed in individuals with HD

In vivo Stimulus-Induced Vasodilation Occurs without IP3 Receptor Activation and May Precede Astrocytic Calcium Increase

publishedVersio

vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase

Calcium-dependent release of vasoactive gliotransmitters is widely assumed to trigger vasodilation associated with rapid increases in neuronal activity. Inconsistent with this hypothesis, intact stimulus-induced vasodilation was observed in inositol 1,4,5-triphosphate (IP 3 ) type-2 receptor (R2) knock-out (KO) mice, in which the primary mechanism of astrocytic calcium increase-the release of calcium from intracellular stores following activation of an IP 3 -dependent pathway-is lacking. Further, our results in wild-type (WT) mice indicate that in vivo onset of astrocytic calcium increase in response to sensory stimulus could be considerably delayed relative to the simultaneously measured onset of arteriolar dilation. Delayed calcium increases in WT mice were observed in both astrocytic cell bodies and perivascular endfeet. Thus, astrocytes may not play a role in the initiation of blood flow response, at least not via calcium-dependent mechanisms. Moreover, an increase in astrocytic intracellular calcium was not required for normal vasodilation in the IP 3 R 2 -KO animals

Cell type specificity of neurovascular coupling in cerebral cortex.

Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease

Cell type specificity of neurovascular coupling in cerebral cortex

Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease. DOI: http://dx.doi.org/10.7554/eLife.14315.00