scholarly journals Heterogeneous Presynaptic Distribution of Munc13 Isoforms at Retinal Synapses and Identification of an Unconventional Bipolar Cell Type with Dual Expression of Munc13 Isoforms: A Study Using Munc13-EXFP Knock-in Mice

2020 ◽  
Vol 21 (21) ◽  
pp. 7848 ◽  
Author(s):  
Kaspar Gierke ◽  
Julia von Wittgenstein ◽  
Maike Hemmerlein ◽  
Jenny Atorf ◽  
Anneka Joachimsthaler ◽  
...  

Munc13 isoforms are constituents of the presynaptic compartment of chemical synapses, where they govern important steps in preparing synaptic vesicles for exocytosis. The role of Munc13-1, -2 and -3 is well documented in brain neurons, but less is known about their function and distribution among the neurons of the retina and their conventional and ribbon-type chemical synapses. Here, we examined the retinae of Munc13-1-, -2-, and -3-EXFP knock-in (KI) mice with a combination of immunocytochemistry, physiology, and electron microscopy. We show that knock-in of Munc13-EXFP fusion proteins did not affect overall retinal anatomy or synapse structure, but slightly affected synaptic transmission. By labeling Munc13-EXFP KI retinae with specific antibodies against Munc13-1, -2 and -3, we found that unlike in the brain, most retinal synapses seem to operate with a single Munc13 isoform. A surprising exception to this rule was type 6 ON bipolar cells, which expressed two Munc13 isoforms in their synaptic terminals, ubMunc13-2 and Munc13-3. The results of this study provide an important basis for future studies on the contribution of Munc13 isoforms in visual signal processing in the mammalian retina.

2022 ◽  
Vol 23 (2) ◽  
pp. 846
Author(s):  
Stanislas Martin ◽  
Audrey Foulon ◽  
Wissam El Hage ◽  
Diane Dufour-Rainfray ◽  
Frédéric Denis

The study aimed to examine the impact of the oropharyngeal microbiome in the pathophysiology of schizophrenia and to clarify whether there might be a bidirectional link between the oral microbiota and the brain in a context of dysbiosis-related neuroinflammation. We selected nine articles including three systemic reviews with several articles from the same research team. Different themes emerged, which we grouped into 5 distinct parts concerning the oropharyngeal phageome, the oropharyngeal microbiome, the salivary microbiome and periodontal disease potentially associated with schizophrenia, and the impact of drugs on the microbiome and schizophrenia. We pointed out the presence of phageoma in patients suffering from schizophrenia and that periodontal disease reinforces the role of inflammation in the pathophysiology of schizophrenia. Moreover, saliva could be an interesting substrate to characterize the different stages of schizophrenia. However, the few studies we have on the subject are limited in scope, and some of them are the work of a single team. At this stage of knowledge, it is difficult to conclude on the existence of a bidirectional link between the brain and the oral microbiome. Future studies on the subject will clarify these questions that for the moment remain unresolved.


1993 ◽  
Vol 10 (3) ◽  
pp. 511-522 ◽  
Author(s):  
William J. Brunken ◽  
Xiao-Tao Jin

AbstractWe investigated the role of 5HT3 receptors in the mammalian retina using electrophysiological techniques to monitor ganglion cell activity. Activation of 5HT3 receptors with the selective agonist 1-phenylbiguanide (PBG) increased the ON responses of ON-center ganglion cells, while decreasing the OFF responses of OFF-center cells. The application of a selective 5HT3 antagonist had a reciprocal effect, namely it reduced the center response in ON-center cells and concomitantly increased the center responses in OFF-center cells. Since putative serotoninergic amacrine cells in the retina are connected specifically to the rod bipolar cell, these agents most likely affect the rod bipolar terminal. These data, together with previous studies, suggest that both 5HT2 and 5HT3 receptors mediate an excitatory influence which serves to facilitate the output from rod bipolar cells, the former via a phosphatidyl inositol second-messenger system, and the latter via a direction channel.


1984 ◽  
Vol 62 (6) ◽  
pp. 709-714 ◽  
Author(s):  
I. M. Mazurkiewicz-Kwilecki

Recently accumulated neurochemical, physiological, and pharmacological evidence strongly supports a role for histamine as a central neurotransmitter. Neurochemical methods, which became available within the last years, allow determination of small amounts of histamine and its metabolites in the brain and make possible future studies of central histamine regulation. The demonstration of histamine H1 and H2 receptors in the brain of several species suggests a possible role for histamine in brain function. Microelectrophysiological studies on single central neurones suggest both excitatory and depressant effects of histamine which are receptor mediated. In addition, brain histamine has been demonstrated to be subject to cyclic variations, to play a role in hormonal regulation, and to be altered by stressful conditions. Several psychotropic drugs significantly affect brain histamine regulation and elicit inhibitory effects on central histamine receptors. These findings bring new approaches and stimulus to further research on the significance of brain histamine.


2018 ◽  
Vol 7 (12) ◽  
pp. R275-R285 ◽  
Author(s):  
Gareth Leng

The brain hosts a vast and diverse repertoire of neuropeptides, a class of signalling molecules often described as neurotransmitters. Here I argue that this description entails a catalogue of misperceptions, misperceptions that feed into a narrative in which information processing in the brain can be understood only through mapping neuronal connectivity and by studying the transmission of electrically conducted signals through chemical synapses. I argue that neuropeptide signalling in the brain involves primarily autocrine, paracrine and neurohormonal mechanisms that do not depend on synaptic connectivity and that it is not solely dependent on electrical activity but on mechanisms analogous to secretion from classical endocrine cells. As in classical endocrine systems, to understand the role of neuropeptides in the brain, we must understand not only how their release is regulated, but also how their synthesis is regulated and how the sensitivity of their targets is regulated. We must also understand the full diversity of effects of neuropeptides on those targets, including their effects on gene expression.


2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Ameer Y. Taha

AbstractIncreased intake of omega-6 rich plant oils such as soybean and corn oil over the past few decades has inadvertently tripled the amount of n-6 linoleic acid (LA, 18:2n-6) in the diet. Although LA is nutritionally “essential”, very little is known about how it affects the brain when present in excess. This review provides an overview on the metabolism of LA by the brain and the effects of excess dietary LA intake on brain function. Pre-clinical evidence suggests that excess dietary LA increases the brain’s vulnerability to inflammation and likely acts via its oxidized metabolites. In humans, excess maternal LA intake has been linked to atypical neurodevelopment, but underlying mechanisms are unknown. It is concluded that excess dietary LA may adversely affect the brain. The potential neuroprotective role of reducing dietary LA merits clinical evaluation in future studies.


2007 ◽  
Vol 30 (2) ◽  
pp. 169-170 ◽  
Author(s):  
Vincent J. Schmithorst

AbstractA parieto-frontal integration theory (P-FIT) model of human intelligence has been proposed based on a review of neuroimaging literature and lesion studies. The P-FIT model provides an important basis for future research. Future studies involving connectivity analyses and an integrative approach of imaging modalities using the P-FIT model should provide vastly increased understanding of the biological bases of intelligence.


2021 ◽  
Vol 8 ◽  
Author(s):  
Liang Guo ◽  
Lingling Zhu

Given combined efforts of neuroscience and immunology, increasing evidence has revealed the critical roles of the immune system in regulating homeostasis and disorders of the central nervous system (CNS). Microglia have long been considered as the only immune cell type in parenchyma, while at the interface between CNS and the peripheral (meninges, choroid plexus, and perivascular space), embryonically originated border-associated macrophages (BAMs) and multiple surveilling leukocytes capable of migrating into and out of the brain have been identified to function in the healthy brain. Hypoxia-induced neuroinflammation is the key pathological procedure that can be detected in healthy people at high altitude or in various neurodegenerative diseases, during which a very thin line between a beneficial response of the peripheral immune system in maintaining brain homeostasis and a pathological role in exacerbating neuroinflammation has been revealed. Here, we are going to focus on the role of the peripheral immune system and its crosstalk with CNS in the healthy brain and especially in hypobaric or ischemic hypoxia-associated neuroinflammation.


2020 ◽  
Vol 68 (7) ◽  
pp. 1208-1216
Author(s):  
Sen Han ◽  
Ting Zhang ◽  
Praveen Kusumanchi ◽  
Nazmul Huda ◽  
Yanchao Jiang ◽  
...  

MicroRNA-7 (miR-7) is a small non-coding RNA, which plays critical roles in regulating gene expression of multiple key cellular processes. MiR-7 exhibits a tissue-specific pattern of expression, with abundant levels found in the brain, spleen, and pancreas. Although it is expressed at lower levels in other tissues, including the liver, miR-7 is involved in both the development of organs and biological functions of cells. In this review, we focus on the mechanisms by which miR-7 controls cell growth, proliferation, invasion, metastasis, metabolism, and inflammation. We also summarize the specific roles of miR-7 in liver diseases. MiR-7 is considered as a tumor suppressor miRNA in hepatocellular carcinoma and is involved in the pathogenesis of hepatic steatosis and hepatitis. Future studies to further define miR-7 functions and its mechanism in association with other types of liver diseases should be explored. An improved understanding from these studies will provide us a useful perspective leading to mechanism-based intervention by targeting miR-7 for the treatment of liver diseases.


2003 ◽  
Vol 90 (4) ◽  
pp. 735-741 ◽  
Author(s):  
Catalina Picó ◽  
Paula Oliver ◽  
Juana Sánchez ◽  
Andreu Palou

The discovery of the production of leptin by the stomach, in addition to its production by adipose tissue, has initiated new investigation into the possible role of this protein in the digestive physiology, in particular in the short-term control of energy balance. Leptin has been identified in the lower half of the stomach glands both in the pepsinogen granules of chief cells and in the granules of a specific endocrine cell type, suggesting that leptin action is exerted by both exocrine and endocrine pathways. Gastric leptin is sensitive to the nutritional state, being rapidly mobilized in response to food intake following fasting, or after the administration of satiety factors; this suggests a role for this protein in the short-term regulation of feeding, acting in collaboration with satiety peptides such as cholecystokinin. Leptin, produced by gastric cells and by adipocytes, could act on both acute and chronic regulation of feeding behaviour respectively, giving information to the brain on the availability of external (food) and internal (fat depots) energy resources, thus participating in short- and long-term satiation.


2012 ◽  
Vol 29 (1) ◽  
pp. 73-81 ◽  
Author(s):  
W.R. TAYLOR ◽  
R.G. SMITH

AbstractStarburst amacrine cells (SBACs) within the adult mammalian retina provide the critical inhibition that underlies the receptive field properties of direction-selective ganglion cells (DSGCs). The SBACs generate direction-selective output of GABA that differentially inhibits the DSGCs. We review the biophysical mechanisms that produce directional GABA release from SBACs and test a network model that predicts the effects of reciprocal inhibition between adjacent SBACs. The results of the model simulations suggest that reciprocal inhibitory connections between closely spaced SBACs should be spatially selective, while connections between more widely spaced cells could be indiscriminate. SBACs were initially identified as cholinergic neurons and were subsequently shown to contain release both acetylcholine and GABA. While the role of the GABAergic transmission is well established, the role of the cholinergic transmission remains unclear.


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