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Cells Nov 2021The heart, also referred to as the dorsal vessel, pumps the insect blood, the hemolymph. The bilateral heart primordia develop from the most dorsally located mesodermal... (Review)
Review
The heart, also referred to as the dorsal vessel, pumps the insect blood, the hemolymph. The bilateral heart primordia develop from the most dorsally located mesodermal cells, migrate coordinately, and fuse to form the cardiac tube. Though much simpler, the fruit fly heart displays several developmental and functional similarities to the vertebrate heart and, as we discuss here, represents an attractive model system for dissecting mechanisms of cardiac aging and heart failure and identifying genes causing congenital heart diseases. Fast imaging technologies allow for the characterization of heartbeat parameters in the adult fly and there is growing evidence that cardiac dysfunction in human diseases could be reproduced and analyzed in , as discussed here for heart defects associated with the myotonic dystrophy type 1. Overall, the power of genetics and unsuspected conservation of genes and pathways puts at the heart of fundamental and applied cardiac research.
Topics: Aging; Animals; Disease Models, Animal; Drosophila; Gene Expression Regulation, Developmental; Heart; Heart Diseases; Humans
PubMed: 34831301
DOI: 10.3390/cells10113078 -
Cold Spring Harbor Protocols Nov 2022This protocol summarizes preparation of the dorsal marginal zone sandwich explant (a.k.a. the "Keller sandwich") and the dorsal isolate from embryos. The Keller...
This protocol summarizes preparation of the dorsal marginal zone sandwich explant (a.k.a. the "Keller sandwich") and the dorsal isolate from embryos. The Keller sandwich is assembled from two early gastrula stage dorsal marginal zone (DMZ) explants. DMZ explants isolated before involution maintain planar patterning processes and block radial signals that might be exchanged between pre- and postinvolution tissues. DMZ explants isolated later in gastrulation, but subsequently opened and flattened may have both planar and radial patterning. The epithelial margins of DMZ explants in Keller sandwiches heal and basal contacts form between the deep layers of the two DMZ explants. The dorsal isolate is dissected from mid- to late-gastrula stage embryos after involution and archenteron formation. Germ-layer contacts between dorsal endoderm, mesoderm, and ectoderm generated by gastrulation movements are maintained in the dorsal isolate. These two explants can be used to study tissue, cell, and subcellular processes relevant to convergent extension, from patterning to cell behaviors, and their collective biomechanics. Skills needed to dissect the Keller sandwich are greater than those needed to dissect animal cap ectoderm and can be mastered in a few weeks; skills needed to dissect the dorsal isolate are similar to those needed to dissect animal caps and can be learned in a week.
Topics: Animals; Gastrula; Mesoderm; Xenopus laevis; Ectoderm; Endoderm
PubMed: 35577523
DOI: 10.1101/pdb.prot097386 -
Frontiers in Molecular Neuroscience 2023Stress may cause prospective escalations in abdominal pain magnitude and accumbal TRPV1 expression, while central neural circuits mediating these stress effects remain...
INTRODUCTION
Stress may cause prospective escalations in abdominal pain magnitude and accumbal TRPV1 expression, while central neural circuits mediating these stress effects remain unclear.
METHODS
Using retrograde tracing methods, we first demonstrated the existence of a medial septal-dorsal lateral septal -accumbal circuit very likely involving social disruption stress-primed escalations in acid-induced writhes and accumbal TRPV1 level. An intersectional viral strategy and virus-carrying hM3Dq and hM4Di DREADDs were, then, employed to selectively modulate GABAergic and cholinergic neuronal activity in medial and dorsal lateral septum.
RESULTS
Exciting medial septal GABAergic neuron was found to prevent social disruption stress-primed escalations in acid-induced writhes and accumbal TRPV1 and PKCε expressions. Likewise, inactivating dorsal lateral septal cholinergic neurons was also effective in abolishing these stress-primed escalations. Inactivating GABAergic neuron in non-stressed animals' medial septum was found to reproduce the stress-primed effects in causing heightened acid-induced writhes and accumbal TRPV1 and PKCε levels.
DISCUSSION
These results, taken together, prompt us to conclude that social disruption stress may produce plastic changes in a newly-identified medial septal-dorsal lateral septal-accumbal circuit. Moreover, medial septal GABAergic hypoactivity and dorsal lateral septal cholinergic hyperactivity are, at least, two likely causes reflecting such stress-produced escalations in abdominal pain magnitude and pain transduction-related protein over-expression in nucleus accumbens.
PubMed: 37152428
DOI: 10.3389/fnmol.2023.1158525 -
Open Mind : Discoveries in Cognitive... Aug 2020According to the influential "Two Visual Pathways" hypothesis, the cortical visual system is segregated into two pathways, with the ventral, occipitotemporal pathway...
According to the influential "Two Visual Pathways" hypothesis, the cortical visual system is segregated into two pathways, with the ventral, occipitotemporal pathway subserving object perception, and the dorsal, occipitoparietal pathway subserving the visuomotor control of action. However, growing evidence suggests that the dorsal pathway also plays a functional role in object perception. In the current article, we present evidence that the dorsal pathway contributes uniquely to the perception of a range of visuospatial attributes that are not redundant with representations in ventral cortex. We describe how dorsal cortex is recruited automatically during perception, even when no explicit visuomotor response is required. Importantly, we propose that dorsal cortex may selectively process visual attributes that can inform the perception of actions on objects and environments, and we consider plausible developmental and cognitive mechanisms that might give rise to these representations. As such, we consider whether naturalistic stimuli, such as real-world solid objects, might engage dorsal cortex more so than simplified or artificial stimuli such as images that do not afford action, and how the use of suboptimal stimuli might limit our understanding of the functional contribution of dorsal cortex to visual perception.
PubMed: 33225195
DOI: 10.1162/opmi_a_00033 -
BioRxiv : the Preprint Server For... Aug 2023Hemispherectomy is a surgical procedure in which an entire hemisphere of a patient's brain is resected or functionally disconnected to manage seizures in individuals...
Hemispherectomy is a surgical procedure in which an entire hemisphere of a patient's brain is resected or functionally disconnected to manage seizures in individuals with drug-resistant epilepsy. Despite the extensive loss of input from both ventral and dorsal visual pathways of one hemisphere, pediatric patients who have undergone hemispherectomy show a remarkably high degree of perceptual function across many domains. In the current study, we sought to understand the extent to which functions of the ventral and dorsal visual pathways reorganize to the contralateral hemisphere following childhood hemispherectomy. To this end, we collected fMRI data from an equal number of left and right hemispherectomy patients who completed tasks that typically elicit lateralized responses from the ventral or the dorsal pathway, namely, word (left ventral), face (right ventral), tool (left dorsal), and global form (right dorsal) perception. Overall, there was greater evidence of functional reorganization in the ventral pathway than in the dorsal pathway. Importantly, because ventral and dorsal reorganization was tested in the very same patients, these results cannot be explained by idiosyncratic factors such as disease etiology, age at the time of surgery, or age at testing. These findings suggest that because the dorsal pathway may mature earlier, it may have a shorter developmental window of plasticity than the ventral pathway and, hence, be less malleable.
PubMed: 37577633
DOI: 10.1101/2023.08.03.551494 -
Frontiers in Behavioral Neuroscience 2022The midline and intralaminar nuclei of the thalamus form a major part of the "limbic thalamus;" that is, thalamic structures anatomically and functionally linked with...
The midline and intralaminar nuclei of the thalamus form a major part of the "limbic thalamus;" that is, thalamic structures anatomically and functionally linked with the limbic forebrain. The midline nuclei consist of the paraventricular (PV) and paratenial nuclei, dorsally and the rhomboid and nucleus reuniens (RE), ventrally. The rostral intralaminar nuclei (ILt) consist of the central medial (CM), paracentral (PC) and central lateral (CL) nuclei. We presently concentrate on RE, PV, CM and CL nuclei of the thalamus. The nucleus reuniens receives a diverse array of input from limbic-related sites, and predominantly projects to the hippocampus and to "limbic" cortices. The RE participates in various cognitive functions including spatial working memory, executive functions (attention, behavioral flexibility) and affect/fear behavior. The PV receives significant limbic-related afferents, particularly the hypothalamus, and mainly distributes to "affective" structures of the forebrain including the bed nucleus of stria terminalis, nucleus accumbens and the amygdala. Accordingly, PV serves a critical role in "motivated behaviors" such as arousal, feeding/consummatory behavior and drug addiction. The rostral ILt receives both limbic and sensorimotor-related input and distributes widely over limbic and motor regions of the frontal cortex-and throughout the dorsal striatum. The intralaminar thalamus is critical for maintaining consciousness and directly participates in various sensorimotor functions (visuospatial or reaction time tasks) and cognitive tasks involving striatal-cortical interactions. As discussed herein, while each of the midline and intralaminar nuclei are anatomically and functionally distinct, they collectively serve a vital role in several affective, cognitive and executive behaviors - as major components of a brainstem-diencephalic-thalamocortical circuitry.
PubMed: 36082310
DOI: 10.3389/fnbeh.2022.964644 -
Molecular Pain 2023Previous studies have confirmed the relationship between chloride homeostasis and pain. However, the role of sodium potassium chloride co-transporter isoform 1 (NKCC1)...
Previous studies have confirmed the relationship between chloride homeostasis and pain. However, the role of sodium potassium chloride co-transporter isoform 1 (NKCC1) in dorsal horn and dorsal root ganglion neurons (DRGs) in spinal cord injury (SCI)-induced neuropathic pain (NP) remains inconclusive. Therefore, we aimed to explore whether suppression of NKCC1 in the spinal cord and DRGs alleviate the NP of adult rats with thoracic spinal cord contusion. Thirty adult female Sprague-Dawley rats (8 week-old, weighing 250-280 g) were randomly divided into three groups with ten animals in each group (sham, SCI, and bumetanide groups). The paw withdrawal mechanical threshold and paw withdrawal thermal latency were recorded before injury (baseline) and on post-injury days 14, 21, 28, and 35. At the end of experiment, western blotting (WB) analysis, quantitative real-time Polymerase Chain Reaction (PCR) and immunofluorescence were performed to quantify NKCC1 expression. Our results revealed that NKCC1 protein expression in the spinal cord and DRGs was significantly up-regulated in rats with SCI. Intraperitoneal treatment of bumetanide (an NKCC1 inhibitor) reversed the expression of NKCC1 in the dorsal horn and DRGs and ameliorated mechanical ectopic pain and thermal hypersensitivities in the SCI rats. Our study demonstrated the occurrence of NKCC1 overexpression in the spinal cord and DRGs in a rodent model of NP and indicated that changes in the peripheral nervous system also play a major role in promoting pain sensitization after SCI.
Topics: Rats; Female; Animals; Rats, Sprague-Dawley; Bumetanide; Ganglia, Spinal; Spinal Cord Dorsal Horn; Spinal Cord Injuries; Neuralgia; Spinal Cord; Hyperalgesia
PubMed: 36760008
DOI: 10.1177/17448069231159855 -
Frontiers in Synaptic Neuroscience 2020Functional diversification along the longitudinal axis of the hippocampus is a rapidly growing concept. Modulation of synaptic transmission by neurotransmitter receptors...
Functional diversification along the longitudinal axis of the hippocampus is a rapidly growing concept. Modulation of synaptic transmission by neurotransmitter receptors may importantly contribute to specialization of local intrinsic network function along the hippocampus. In the present study, using transverse slices from the dorsal and the ventral hippocampus of adult rats and recordings of evoked field postsynaptic excitatory potentials (fEPSPs) from the CA1 stratum radiatum, we aimed to compare modulation of synaptic transmission between the dorsal and the ventral hippocampus. We found that transient heterosynaptic depression (tHSD, <2 s), a physiologically relevant phenomenon of regulation of excitatory synaptic transmission induced by paired stimulation of two independent inputs to stratum radiatum of CA1 field, has an increased magnitude and duration in the ventral hippocampus, presumably contributing to increased input segregation in this segment of the hippocampus. GABA receptors, GABA receptors, adenosine A1 receptors and L-type voltage-gated calcium channels appear to contribute differently to tHSD in the two hippocampal segments; GABARs play a predominant role in the ventral hippocampus while both GABARs and A1Rs play important roles in the dorsal hippocampus. Activation of GABA receptors by an exogenous agonist, baclofen, robustly and reversibly modulated both the initial fast and the late slow components of excitatory synaptic transmission, expressed by the fEPSPslope and fEPSP decay time constant (fEPSP), respectively. Specifically, baclofen suppressed fEPSP slope more in the ventral than in the dorsal hippocampus and enhanced fEPSP more in the dorsal than in the ventral hippocampus. Also, baclofen enhanced paired-pulse facilitation in the two hippocampal segments similarly. Blockade of GABA receptors did not affect basal paired-pulse facilitation in either hippocampal segment. We propose that the revealed dorsal-ventral differences in modulation of synaptic transmission may provide a means for specialization of information processing in the local neuronal circuits, thereby significantly contributing to diversifying neuronal network functioning along the dorsal-ventral axis of hippocampus.
PubMed: 32625076
DOI: 10.3389/fnsyn.2020.00024 -
Vision Research Sep 2021Rubin's face-vase illusion demonstrates how one can switch back and forth between two different interpretations depending on how the figure outlines are assigned. In the...
Rubin's face-vase illusion demonstrates how one can switch back and forth between two different interpretations depending on how the figure outlines are assigned. In the primate visual system, assigning ownership along figure borders is encoded by neurons called the border ownership (BO) cells. Studies show that the responses of these neurons not only depend on the local features within their receptive fields, but also on contextual information. Despite two decades of studies on BO neurons, the ownership assignment mechanism in the brain is still unknown. Here, we propose a hierarchical recurrent model grounded on the hypothesis that neurons in the dorsal stream provide the context required for ownership assignment. Our proposed model incorporates early recurrence from the dorsal pathway as well as lateral modulations within the ventral stream. While dorsal modulations initiate the response difference to figure on either side of the border, lateral modulations enhance the difference. We found responses of our dorsally-modulated BO cells, similar to their biological counterparts, are invariant to size, position and solid/outlined figures. Moreover, our model BO cells exhibit comparable levels of reliability in the ownership signal to biological BO neurons. We found dorsal modulations result in high levels of accuracy and robustness for BO assignments in complex scenes compared to previous models based on ventral feedback. Finally, our experiments with illusory contours suggest that BO encoding could explain the perception of such contours in higher processing stages in the brain.
Topics: Animals; Ownership; Pattern Recognition, Visual; Photic Stimulation; Reproducibility of Results; Visual Cortex
PubMed: 34023589
DOI: 10.1016/j.visres.2021.04.009 -
Developmental Cognitive Neuroscience Dec 2023Hemispherectomy is a surgical procedure in which an entire hemisphere of a patient's brain is resected or functionally disconnected to manage seizures in individuals...
Hemispherectomy is a surgical procedure in which an entire hemisphere of a patient's brain is resected or functionally disconnected to manage seizures in individuals with drug-resistant epilepsy. Despite the extensive loss of both ventral and dorsal visual pathways in one hemisphere, pediatric patients who have undergone hemispherectomy show a remarkably high degree of perceptual function across many domains. In the current study, we sought to understand the extent to which functions of the ventral and dorsal visual pathways reorganize to the contralateral hemisphere following childhood hemispherectomy. To this end, we collected fMRI data from an equal number of left and right hemispherectomy patients who completed tasks that typically elicit lateralized responses from the ventral or the dorsal pathway, namely, word (left ventral), face (right ventral), tool (left dorsal), and global form (right dorsal) perception. Overall, there was greater evidence of functional reorganization in the ventral pathway than in the dorsal pathway. Importantly, because ventral and dorsal reorganization was tested within the very same patients, these results cannot be explained by idiosyncratic factors such as disease etiology, age at the time of surgery, or age at testing. These findings suggest that because the dorsal pathway may mature earlier, it may have a shorter developmental window of plasticity than the ventral pathway and, hence, be less malleable after perturbation.
Topics: Humans; Child; Hemispherectomy; Visual Pathways; Brain; Magnetic Resonance Imaging
PubMed: 37976921
DOI: 10.1016/j.dcn.2023.101323