To better understand the function of cholinergic projection neurons in the ventral pallidum (VP), we examined behavioral responses to appetitive (APP) and aversive (AV) odors that elicited approach or avoidance, respectively. Exposure to each odor increased cFos expression and calcium signaling in VP cholinergic neurons. Activity and Cre-dependent viral vectors selectively labeled VP cholinergic neurons that were activated and reactivated in response to either APP or AV odors, but not both, identifying two non-overlapping populations of VP cholinergic neurons differentially activated by the valence of olfactory stimuli.
View Article and Find Full Text PDFNeurons of the basal forebrain nucleus basalis and posterior substantia innominata (NBM/SI) comprise the major source of cholinergic input to the basolateral amygdala (BLA). Using a genetically-encoded acetylcholine (ACh) sensor in mice, we demonstrate that BLA-projecting cholinergic neurons can "learn" the association between a naïve tone and a foot shock (training) and release ACh in the BLA in response to the conditioned tone 24h later (recall). In the NBM/SI cholinergic neurons express the immediate early gene, Fos following both training and memory recall.
View Article and Find Full Text PDFNeurons of the basal forebrain nucleus basalis and posterior substantia innominata (NBM/SI) comprise the major source of cholinergic input to the basolateral amygdala (BLA). Using a genetically encoded acetylcholine (ACh) sensor in mice, we demonstrate that BLA-projecting cholinergic neurons can 'learn' the association between a naive tone and a foot shock (training) and release ACh in the BLA in response to the conditioned tone 24 hr later (recall). In the NBM/SI cholinergic neurons express the immediate early gene, Fos following both training and memory recall.
View Article and Find Full Text PDFThe ventral pallidum (VP) mediates motivated behaviors largely via the action of VP GABA and glutamatergic neurons. In addition to these neuronal subtypes, there is a population of cholinergic projection neurons in the VP, whose functional significance remains unclear. To understand the functional role of VP cholinergic neurons, we first examined behavioral responses to an appetitive (APP) odor that elicited approach, and an aversive (AV) odor that led to avoidance.
View Article and Find Full Text PDFAcetylcholine plays an essential role in fundamental aspects of cognition. Studies that have mapped the activity and functional connectivity of cholinergic neurons have shown that the axons of basal forebrain cholinergic neurons innervate the pallium with far more topographical and functional organization than was historically appreciated. Together with the results of studies using new probes that allow release of acetylcholine to be detected with high spatial and temporal resolution, these findings have implicated cholinergic networks in 'binding' diverse behaviours that contribute to cognition.
View Article and Find Full Text PDFBackground: Reported childhood adversity (CA) is associated with development of depression in adulthood and predicts a more severe course of illness. Although elevated serotonin 1A receptor (5-HTR) binding potential, especially in the raphe nuclei, has been shown to be a trait associated with major depression, we did not replicate this finding in an independent sample using the partial agonist positron emission tomography tracer [C]CUMI-101. Evidence suggests that CA can induce long-lasting changes in expression of 5-HTR, and thus, a history of CA may explain the disparate findings.
View Article and Find Full Text PDFBackground: In the context of the largest dengue outbreak in the state of Kerala, India in 2017, along with global evidence of changing epidemiology of dengue virus and its distribution, this study was planned to understand the epidemiological pattern of dengue infection and contemplate the clinical presentations of different serotypes.
Methods: This cross-sectional study was conducted in the Thiruvananthapuram and Kollam districts of Kerala, India, spanning 3 y from 2017 to 2019. We recruited adult patients based on the World Health Organization case definition of probable dengue fever to study their virological, spatial and clinical characteristics.
IEEE Trans Vis Comput Graph
March 2023
Recent advances in high-resolution microscopy have allowed scientists to better understand the underlying brain connectivity. However, due to the limitation that biological specimens can only be imaged at a single timepoint, studying changes to neural projections over time is limited to observations gathered using population analysis. In this article, we introduce NeuRegenerate, a novel end-to-end framework for the prediction and visualization of changes in neural fiber morphology within a subject across specified age-timepoints.
View Article and Find Full Text PDFIEEE Trans Vis Comput Graph
December 2022
We introduce NeuroConstruct, a novel end-to-end application for the segmentation, registration, and visualization of brain volumes imaged using wide-field microscopy. NeuroConstruct offers a Segmentation Toolbox with various annotation helper functions that aid experts to effectively and precisely annotate micrometer resolution neurites. It also offers an automatic neurites segmentation using convolutional neuronal networks (CNN) trained by the Toolbox annotations and somas segmentation using thresholding.
View Article and Find Full Text PDFIntroduction: Novel environment stimulation is thought to have an important role in cognitive development and has been shown to encourage exploratory behavior in rats. However, psychopathology or perceived danger or stress can impede this exploratory drive. The balance between brain circuits controlling the exploratory drive elicited by a novel environment, and the avoidance response to stressors, is not well understood.
View Article and Find Full Text PDFLoudness dependence of auditory evoked potentials (LDAEP) has long been considered to reflect central basal serotonin transmission. However, the relationship between LDAEP and individual serotonin receptors and transporters has not been fully explored in humans and may involve other neurotransmitter systems. To examine LDAEP's relationship with the serotonin system, we performed PET using serotonin-1A (5-HT) imaging via [C]CUMI-101 and serotonin transporter (5-HTT) imaging via [C]DASB on a mixed sample of healthy controls (n = 4: 4 females, 0 males), patients with unipolar (MDD, n = 11: 4 females, 7 males) and bipolar depression (BD, n = 8: 4 females, 4 males).
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
September 2020
Background: Lithium, one of the few effective treatments for bipolar depression (BPD), has been hypothesized to work by enhancing serotonergic transmission. Despite preclinical evidence, it is unknown whether lithium acts via the serotonergic system. Here we examined the potential of serotonin transporter (5-HTT) or serotonin 1A receptor (5-HT) pre-treatment binding to predict lithium treatment response and remission.
View Article and Find Full Text PDFThe molecular weight (Mw) of hyaluronic acid (HA) determines its suitability for medical and cosmetic applications. Here, we characterize in vitro and in vivo HA synthesis of streptococcal HA synthases (HASs) with a special focus on HA Mw. To date, four streptococcal HA producers are described (Streptococcus equi subsp.
View Article and Find Full Text PDFDopamine D4 receptor (DRD4) dysregulation is associated with a variety of behaviors including novelty-seeking, approach avoidance, and ADHD. DRD4 has also been shown to interact with the environment to produce changes in behavior and longevity. The present study sought to examine the role of DRD4 on cocaine-seeking behavior in the conditioned place preference (CPP) test and determine its effects on extinction and reinstatement in adult wild-type (WT), heterozygous (HT), and knockout (KO) mice.
View Article and Find Full Text PDFPurpose: To determine if one venous blood sample can substitute full arterial sampling in quantitative modeling for multiple positron emission tomography (PET) radiotracers using simultaneous estimation of the input function (SIME).
Procedures: Participants underwent PET imaging with [C]ABP688, [C]CUMI-101, and [C]DASB. Full arterial sampling and additional venous blood draws were performed for quantification with the arterial input function (AIF) and SIME using one arterial or venous (vSIME) sample.
Based on recent molecular genetics, as well as functional and quantitative anatomical studies, the basal forebrain (BF) cholinergic projections, once viewed as a diffuse system, are emerging as being remarkably specific in connectivity. Acetylcholine (ACh) can rapidly and selectively modulate activity of specific circuits and ACh release can be coordinated in multiple areas that are related to particular aspects of cognitive processing. This review discusses how a combination of multiple new approaches with more established techniques are being used to finally reveal how cholinergic neurons, together with other BF neurons, provide temporal structure for behavior, contribute to local cortical state regulation, and coordinate activity between different functionally related cortical circuits.
View Article and Find Full Text PDFObjective: To assess the sanitary condition and water quality of household wells and to depict it spatially using Geographic Information System (GIS) in an urban area of Trivandrum, Kerala state, India.
Study Design: A community-based cross-sectional census-type study.
Methods: Study was conducted in an urban area of Trivandrum.
IEEE Trans Vis Comput Graph
August 2018
Wide-field microscopes are commonly used in neurobiology for experimental studies of brain samples. Available visualization tools are limited to electron, two-photon, and confocal microscopy datasets, and current volume rendering techniques do not yield effective results when used with wide-field data. We present a workflow for the visualization of neuronal structures in wide-field microscopy images of brain samples.
View Article and Find Full Text PDFCancer Prev Res (Phila)
August 2018
Head and neck squamous cell carcinoma (HNSCC) accounts for 300,000 deaths per year worldwide, and overall survival rates have shown little improvement over the past three decades. Current treatment methods including surgery, chemotherapy, and radiotherapy leave patients with secondary morbidities. Thus, treatment of HNSCC may benefit from exploration of natural compounds as chemopreventive agents.
View Article and Find Full Text PDFAlbert Jonsen and Stephen Toulmin have argued that the best way to resolve the complex issues in medical settings is to focus on the actual details of cases and then determine what to do in the given cases. This approach to medical decision-making, labeled "casuistry," has met with much criticism. In response, Carson Strong has attempted to save much of Jonsen and Toulmin's version of casuistry.
View Article and Find Full Text PDFDespite therapeutic advancements, there has been little change in the survival of patients with head and neck squamous cell carcinoma (HNSCC). Recent results suggest that cancer-associated fibroblasts (CAF) drive progression of this disease. Here, we report that autophagy is upregulated in HNSCC-associated CAFs, where it is responsible for key pathogenic contributions in this disease.
View Article and Find Full Text PDFMajor depressive disorder (MDD) is a debilitating condition that affects over 14 million Americans. Remission occurs only in a minority of individuals after first-line antidepressant treatment (∼35%); predictors of treatment outcome are therefore needed. Using PET imaging with a radiotracer specific for the serotonin transporter (5-HTT), C-McN5652, we found that patients with MDD who did not achieve remission after 12 mo of naturalistic treatment had lower pretreatment midbrain and amygdala binding than healthy volunteers.
View Article and Find Full Text PDFGibbs developed the thermodynamics of a liquid-vapor system by introducing the idea of a "dividing surface" a hypothetical surface that separates the system into two homogeneous phases. The area and curvatures of a conveniently chosen dividing surface, the "surface of tension", are used to account for the effects of the smooth variation of properties across the actual transition layer between the phases. Tolman (1948, 1949) considered a more detailed model of the interfacial region and obtained expressions for surface tension (σ) and the location of the surface of tension.
View Article and Find Full Text PDFRecent developments in the generation of neuronal population-specific, genetically modified mouse lines have allowed precise identification and selective stimulation of cholinergic neurons in vivo. Although considerably less laborious than studies conducted with post hoc identification of cholinergic neurons by immunostaining, it is not known whether the genetically based labeling procedures that permit in vivo identification are electrophysiologically benign. In this study, we use mice carrying a bacterial artificial chromosome transgene that drives expression of a tau-green fluorescent fusion protein specifically in cholinergic neurons.
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