GABAergic interneurons can pace the activity of principal cells and are thus critically involved in the generation of oscillatory and synchronous network activity. The specific role of various GABAergic subpopulations, however, has remained elusive. This is in part attributable to the scarcity of certain GABAergic neurons and the difficulty of identifying them in slices obtained from brain regions in which anatomical structures are not readily recognizable in the live preparation. To facilitate the functional analysis of GABAergic interneurons, we generated transgenic mice in which the enhanced green fluorescent protein (EGFP) was specifically expressed in parvalbumin-positive neurons. The high fidelity of expression obtained using bacterial artificial chromosome transgenes resulted in EGFP-labeled neurons in nearly all brain regions known to contain parvalbumin-expressing neurons. Immunocytochemical analysis showed that EGFP expression was primarily restricted to parvalbumin-positive cells. In addition to cell body labeling, EGFP expression was high enough in many neurons to enable the visualization of dendritic structures. With the help of these mice, we investigated the presence of electrical coupling between parvalbumin-positive cells in brain slices obtained from young and adult animals. In dentate gyrus basket cells, electrical coupling was found in slices from young [postnatal day 14 (P14)] and adult (P28 and P42) animals, but both strength and incidence of coupling decreased during development. However, electrical coupling between parvalbumin-positive multipolar cells in layer II/III of the neocortex remains unaltered during development. Yet another developmental profile of electrical coupling was found between layer II/III parvalbumin-positive cells and excitatory principal cells. Between these neurons, electrical coupling was found at P14 but not at P28. The results indicate that the presence and strength of electrical coupling is developmentally regulated with respect to brain area and cell type.
Abstract A specialized neurogenic niche along the ventricles accumulates millions of progenitor cells in the developing brain. After mitosis, fate-committed daughter cells delaminate from this germinative zone. Considering the high number of cell divisions and delaminations taking place during embryonic development, brain malformations caused by ectopic proliferation of misplaced progenitor cells are relatively rare. Here, we report that a process we term developmental anoikis distinguishes the pathological detachment of progenitor cells from the normal delamination of daughter neuroblasts in the developing mouse neocortex. We identify the endocannabinoid-metabolizing enzyme abhydrolase domain containing 4 (ABHD4) as an essential mediator for the elimination of pathologically detached cells. Consequently, rapid ABHD4 downregulation is necessary for delaminated daughter neuroblasts to escape from anoikis. Moreover, ABHD4 is required for fetal alcohol-induced apoptosis, but not for the well-established form of developmentally controlled programmed cell death. These results suggest that ABHD4-mediated developmental anoikis specifically protects the embryonic brain from the consequences of sporadic delamination errors and teratogenic insults.
Event Abstract Back to Event Molecular architecture of endocannabinoid signaling in the dorsal horn of the spinal cord mediating antinociception Rita Nyilas1, Laura C. Gregg2, Ken Mackie3, Masahiko Watanabe4, Andreas Zimmer5, Andrea G. Hohmann2 and István Katona1* 1 Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary 2 Department of Psychology, University of Georgia, Georgia 3 Department of Psychological and Brain Sciences, Indiana University, United States 4 Department of Anatomy, Hokkaido University School of Medicine, Japan 5 Institute of Molecular Psychiatry, University of Bonn, Germany Cannabinoid receptor agonists exert a highly potent antinociceptive effect in acute and chronic pain indicating that endogenous cannabinoids may have a pivotal role in the regulation of nociception. However, the underlying molecular basis of endocannabinoid signaling has remained elusive at the spinal level. Because the lipid messenger 2-arachidonoylglycerol (2-AG) is emerging as a candidate molecule for being the predominant synaptic endocannabinoid, we aimed to characterize the precise molecular architecture of 2-AG signaling and its involvement in nociception in the spinal cord. Non-radioactive in situ hybridization revealed that dorsal horn neurons widely express the mRNA of diacylglycerol lipase-alpha (DGL-α), the synthesizing enzyme of 2-AG. Peroxidase-based immunocytochemistry demonstrated high levels of DGL-α protein and CB1 cannabinoid receptor, the receptor of 2-AG, in the superficial dorsal horn, at the first site of modulation of the ascending pain pathway. High-resolution immunoelectron microscopy uncovered presynaptic localization of CB1 and postsynaptic positioning of DGL-α at nociceptive synapses formed by Aδ- and C-fibers. Furthermore, DGL-α in postsynaptic elements receiving nociceptive inputs colocalized with metabotropic glutamate receptor 5 (mGluR5) known to trigger 2-AG release. Finally, intrathecal induction of mGluR5 evoked stress-induced analgesia through activation of DGL-α and CB1 in the spinal cord. Taken together, these findings underlie the key role of 2-AG-mediated retrograde suppression of nociceptive transmission at the spinal level. The striking positioning of the molecular players of 2-AG synthesis and action at nociceptive excitatory synapses suggests that pharmacological regulation of intrinsic spinal 2-AG levels may have important therapeutic potential in the regulation of pain sensation. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Pathophysiology and neurology - non-degenerative disorders Citation: Nyilas R, Gregg LC, Mackie K, Watanabe M, Zimmer A, Hohmann AG and Katona I (2009). Molecular architecture of endocannabinoid signaling in the dorsal horn of the spinal cord mediating antinociception. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.035 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Feb 2009; Published Online: 27 Feb 2009. * Correspondence: István Katona, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary, katona@koki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Rita Nyilas Laura C Gregg Ken Mackie Masahiko Watanabe Andreas Zimmer Andrea G Hohmann István Katona Google Rita Nyilas Laura C Gregg Ken Mackie Masahiko Watanabe Andreas Zimmer Andrea G Hohmann István Katona Google Scholar Rita Nyilas Laura C Gregg Ken Mackie Masahiko Watanabe Andreas Zimmer Andrea G Hohmann István Katona PubMed Rita Nyilas Laura C Gregg Ken Mackie Masahiko Watanabe Andreas Zimmer Andrea G Hohmann István Katona Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.
Presynaptic CB1 cannabinoid receptors control neurotransmitter release in a synapse-specific manner at different temporal scales. While the molecular mechanisms of on-demand, so-called phasic forms of endocannabinoid-mediated synaptic plasticity are well-described, the mechanistic attributes of the persistent, so-called tonic form of synaptic cannabinoid signaling remain debated. Unlike phasic endocannabinoid signaling, we found that the synaptic cannabinoid tone controls release probability in the absence of the two major endocannabinoid-producing enzymes at hippocampal GABAergic synapses. Direct correlative measurement of the physiological, anatomical, and molecular parameters at single identified synapses revealed that the nanoscale receptor/effector ratio around release sites is the key determinant of the synaptic cannabinoid tone. Moreover, in vivo treatment by the psychoactive cannabis substance Δ 9-tetrahydrocannabinol disrupts the precise molecular stoichiometry and tonic cannabinoid signaling. These findings imply that the nanoscale stoichiometry of constitutively active presynaptic receptors coupling to the release machinery plays a central role in calibrating synapse-specific release probability.
Aims and scope.EJN publishes original research articles and reviews in the broad fields of molecular, cellular, systems, behavioral, and cognitive neurosciences.EJN aims to advance our understanding of the nervous system in health and disease, thereby improving the diagnosis and treatment of neuro psychiatric and neurodegenerative disorders.
The increasing prevalence of cannabis use during pregnancy has raised medical concerns, primarily related to Δ9-tetrahydrocannabinol (THC), which readily crosses the placenta and affects fetal brain development. Previous research has identified dopaminergic alterations related to maternal THC consumption. However, the consequences that prenatal cannabis exposure (PCE) has on striatum-based processing during reward pursuit have not been determined. Here, we characterize PCE rats during food or opioid-maintained reward seeking. We find that the supramotivational phenotype of PCE rats is independent of value-based processing and is instead related to augmented reinforcing efficiency of opioid rewards. Our findings reveal that prenatal THC exposure leads to increased cue-evoked dopamine responses and an overrepresentation of effort-driven striatal encoding patterns. Recapitulating clinical findings, drug-related PCE adaptations were more pronounced in males, who showed increased vulnerability for relapse. Collectively, these findings indicate that prenatal THC exposure in male rats engenders a pronounced neurodevelopmental susceptibility to addiction-like disorders.
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