Glycine exerts potent inhibitory actions on mammalian olfactory bulb neurons

1994 ◽  
Vol 71 (2) ◽  
pp. 761-767 ◽  
Author(s):  
P. Q. Trombley ◽  
G. M. Shepherd
Keyword(s):  
Spinal Cord ◽  
Olfactory Bulb ◽  
Hill Coefficient ◽  
Mammalian Brain ◽  
Glycine Receptors ◽  
Low Concentrations ◽  
Biological Studies ◽  
Tufted Cells ◽  
The Brain ◽  
Olfactory Bulb Neurons

1. It is generally presumed that gamma-aminobutyric acid (GABA) mediates inhibition in the mammalian brain, whereas glycine is restricted to the brain stem and spinal cord. Recent immunocytochemical and molecular biological studies have demonstrated, however, a widespread distribution of glycine receptors through-out the CNS, including the olfactory bulb. To explore the functional significance of glycine receptors in the olfactory bulb we have used primary culture and whole-cell voltage-clamp recording techniques to test the hypothesis that glycine, as well as GABA, exerts inhibitory actions on olfactory bulb neurons. 2. Cultures of olfactory bulb neurons contain two primary populations of morphologically distinct neurons, mitral/tufted cells and interneurons (granule and periglomerular cells). In all mitral/tufted cells and interneurons examined, both glycine and GABA evoked concentration-dependent desensitizing currents mediated by chloride, similar to those seen in mammalian neurons elsewhere in the brain and spinal cord. 3. The median effective concentration (EC50) for glycine was 125 microM, with a Hill coefficient of 1.7, whereas the EC50 and Hill coefficient for GABA were 52 microM and 1.8, respectively. These values are similar to values previously reported for other central neurons. 4. At moderate concentrations (> 1 microM) strychnine nonselectively antagonized both glycine- and GABA-evoked currents. At low concentrations (< or = 1 microM) strychnine blocked glycine-mediated currents but had little effect on GABA-mediated currents. Similarly, picrotoxin was a nonselective antagonist for glycine- and GABA-mediated currents at high concentrations (100 microM), but was selective for GABA at low concentrations (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Differential modulation by zinc and copper of amino acid receptors from rat olfactory bulb neurons

1996 ◽  
Vol 76 (4) ◽  
pp. 2536-2546 ◽  
Author(s):  
P. Q. Trombley ◽  
G. M. Shepherd
Keyword(s):  
Amino Acid ◽  
Olfactory Bulb ◽  
Nmda Receptors ◽  
Gaba Receptors ◽  
Gamma Aminobutyric Acid ◽  
Differential Modulation ◽  
Glycine Receptors ◽  
Amino Acid Receptors ◽  
High Concentrations ◽  
Olfactory Bulb Neurons

1. The olfactory bulb contains high concentrations of zinc and copper. Whole cell recording techniques were used to examine the modulatory actions of zinc and copper on N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid (GABA), and glycine receptors on rat olfactory bulb neurons in culture and acutely isolated from adult animals. 2. Zinc and copper were effective antagonists of both NMDA-and GABA-mediated currents. The median inhibiting concentrations (IC50s) for zinc were 19 microM for NMDA receptors and 17 microM for GABA receptors. The IC50s for copper were 22 microM for NMDA receptors and 18 microM for GABA receptors. 3. Zinc and copper (100 microM) had no effect on the steady-state, desensitized component of currents evoked by high concentrations of glycine (300 microM). In contrast, when low, nondesensitizing concentrations of glycine (30 microM) were used, 100 microM zinc dramatically potentiated the current and 100 microM copper blocked the current. 4. The effects of zinc and copper on NMDA-, GABA-, or glycine-mediated currents were not voltage dependent, irrespective of whether the effect was potentiation or inhibition. 5. These results provide the first evidence for an inhibitory effect of copper on NMDA receptors, and the first evidence that the effects of zinc and copper on glycine receptors are dependent on the state of the receptor. These results suggest that endogenous zinc and copper may act as allosteric neuromodulators of amino acid receptors on olfactory bulb neurons. Furthermore, zinc and copper may provide a mechanism for differential modulation of inhibitory transmission because of their distinct effects on glycine versus GABA receptors.

Interactions Between GABA and Glycine at Inhibitory Amino Acid Receptors on Rat Olfactory Bulb Neurons

1999 ◽  
Vol 82 (6) ◽  
pp. 3417-3422 ◽  
Author(s):  
Paul Q. Trombley ◽  
Brook J. Hill ◽  
Michelle S. Horning
Keyword(s):  
Amino Acid ◽  
Olfactory Bulb ◽  
Cell Voltage ◽  
The Other ◽  
Amino Acid Receptors ◽  
Inhibitory Synaptic Transmission ◽  
Low Concentrations ◽  
Subsequent Application ◽  
Cross Inhibition ◽  
Olfactory Bulb Neurons

Whole cell voltage-clamp electrophysiology was used to examine interactions between GABA and glycine at inhibitory amino acid receptors on rat olfactory bulb neurons in primary culture. Membrane currents evoked by GABA and glycine were selectively inhibited by low concentrations of bicuculline and strychnine, respectively, suggesting that they activate pharmacologically distinct receptors. However, GABA- and glycine-mediated currents showed cross-inhibition when the two amino acids were applied sequentially. Application of one amino acid inhibited the response to immediate subsequent application of the other. In the majority of neurons, GABA inhibited subsequent glycine-evoked currents and glycine inhibited subsequent GABA-evoked currents. In a small proportion of neurons, however, GABA inhibited glycine-evoked currents but glycine had little effect on GABA-evoked currents. The reverse was true in other neurons, suggesting that alterations in chloride gradients alone did not account for the cross-inhibition. Furthermore, no cross-inhibition was observed between GABA- and glycine-evoked currents in some neurons. The amplitude of the current evoked by the coapplication of saturating concentrations of GABA and glycine in these neurons was nearly the sum of the currents evoked by GABA and glycine alone. In contrast, the currents were not additive in neurons demonstrating cross-inhibition. These results suggest that olfactory bulb neurons heterogeneously express a population of inhibitory amino acid receptors that can bind either GABA or glycine. Interactions between GABA and glycine at inhibitory amino acid receptors may provide a mechanism to modulate inhibitory synaptic transmission.

scholarly journals Purinergic receptors activating rapid intracellular Ca2+ increases in microglia

2005 ◽  
Vol 2 (2) ◽  
pp. 125-138 ◽  
Author(s):  
ALAN R. LIGHT ◽  
YING WU ◽  
RONALD W. HUGHEN ◽  
PETER B. GUTHRIE
Keyword(s):  
Spinal Cord ◽  
Tissue Injury ◽  
Response Curves ◽  
Calcium Response ◽  
Low Concentrations ◽  
Peripheral Immune Cells ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Shape Changes ◽  
Potency Order

We provide both molecular and pharmacological evidence that the metabotropic, purinergic, P2Y6, P2Y12 and P2Y13 receptors and the ionotropic P2X4 receptor contribute strongly to the rapid calcium response caused by ATP and its analogues in mouse microglia. Real-time PCR demonstrates that the most prevalent P2 receptor in microglia is P2Y6 followed, in order, by P2X4, P2Y12, and P2X7 = P2Y13. Only very small quantities of mRNA for P2Y1, P2Y2, P2Y4, P2Y14, P2X3 and P2X5 were found. Dose-response curves of the rapid calcium response gave a potency order of: 2MeSADP>ADP=UDP=IDP=UTP>ATP>BzATP, whereas A2P4 had little effect. Pertussis toxin partially blocked responses to 2MeSADP, ADP and UDP. The P2X4 antagonist suramin, but not PPADS, significantly blocked responses to ATP. These data indicate that P2Y6, P2Y12, P2Y13 and P2X receptors mediate much of the rapid calcium responses and shape changes in microglia to low concentrations of ATP, presumably at least partly because ATP is rapidly hydrolyzed to ADP. Expression of P2Y6, P2Y12 and P2Y13 receptors appears to be largely glial in the brain, so that peripheral immune cells and CNS microglia share these receptors. Thus, purinergic, metabotropic, P2Y6, P2Y12, P2Y13 and P2X4 receptors might share a role in the activation and recruitment of microglia in the brain and spinal cord by widely varying stimuli that cause the release of ATP, including infection, injury and degeneration in the CNS, and peripheral tissue injury and inflammation which is signaled via nerve signaling to the spinal cord.

scholarly journals Ultrarapid Inflammation of the Olfactory Bulb After Spinal Cord Injury: Protective Effects of the Granulocyte Colony-Stimulating Factor on Early Neurodegeneration in the Brain

2021 ◽  
Vol 13 ◽  
Author(s):  
Muh-Shi Lin ◽  
I-Hsiang Chiu ◽  
Chai-Ching Lin
Keyword(s):  
Spinal Cord ◽  
Olfactory Bulb ◽  
Neurotrophic Factors ◽  
Olfactory Receptors ◽  
Olfactory Dysfunction ◽  
Granulocyte Colony Stimulating Factor ◽  
Expression Levels ◽  
Cord Injury ◽  
The Brain ◽  
Stimulating Factor

The correlation among olfactory dysfunction, spinal cord injury (SCI), subjective cognitive decline, and neurodegenerative dementia has been established. Impaired olfaction is considered a marker for neurodegeneration. Hence, there is a need to examine if SCI leads to olfactory dysfunction. In this study, the brain tissue of mice with spinal cord hemisection injury was subjected to microarray analysis. The mRNA expression levels of olfactory receptors in the brain began to decline at 8 h post-SCI. SCI promoted neuroinflammation, downregulated the expression of olfactory receptors, decreased the number of neural stem cells (NSCs), and inhibited the production of neurotrophic factors in the olfactory bulbs at 8 h post-SCI. In particular, the SCI group had upregulated mRNA and protein expression levels of glial fibrillary acidic protein (GFAP; a marker of astrocyte reactivation) and pro-inflammatory mediators [IL-1β, IL-6, and Nestin (marker of NSCs)] in the olfactory bulb compared to levels in the sham control group. The mRNA expression levels of olfactory receptors (Olfr1494, Olfr1324, Olfr1241, and Olfr979) and neurotrophic factors [brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and nerve growth factor (NGF)] were downregulated in the olfactory bulb of the SCI group mice at 8 h post-SCI. The administration of granulocyte colony-stimulating factor (G-CSF) mitigated these SCI-induced pathological changes in the olfactory bulb at 8 h post-SCI. These results indicate that the olfactory bulb is vulnerable to environmental damage even if the lesion is located at sites distant from the brain, such as the spinal cord. Additionally, SCI initiated pathological processes, including inflammatory response, and impaired neurogenesis, at an early stage. The findings of this study will provide a basis for future studies on pathological mechanisms of early neurodegenerative diseases involving the olfactory bulb and enable early clinical drug intervention.

Properties and modulation of a calcium-activated potassium channel in rat olfactory bulb neurons

1993 ◽  
Vol 69 (5) ◽  
pp. 1433-1442 ◽  
Author(s):  
T. M. Egan ◽  
D. Dagan ◽  
I. B. Levitan
Keyword(s):  
Olfactory Bulb ◽  
Single Channel ◽  
Membrane Surface ◽  
Reversal Potential ◽  
Mammalian Brain ◽  
Kca Channels ◽  
Transmembrane Voltage ◽  
Extracellular Side ◽  
Olfactory Bulb Neurons

1. Single calcium-activated potassium channels (KCa channels) were recorded from membrane patches of rat olfactory bulb neurons in culture. Only one kind of KCa channel was seen, and it was present in approximately 50% of detached patches. 2. This channel, like maxi-KCa channels of other tissues, had a single-channel conductance of 270 pS, a reversal potential (Erev) of 0 mV in symmetrical K+, and was highly selective for K+ over Na+ and Cl-. 3. The KCa channel was blocked by d-tubocurarine (d-TC) on the cytoplasmic side, and charybdotoxin (CTX) on the extracellular side. This pharmacology is identical to that of one type of KCa channel from rat brain, observed previously in artificial bilayers and called the type 1 KCa channel. 4. The probability that the channel was in the open state (Po) increased with membrane depolarization. The position of the Po versus transmembrane voltage (Vm) curve was shifted by changes in [Ca2+]i so that the channel was open more often in higher [Ca2+]i. The gating kinetics resembled those of the type 1 KCa channel observed in bilayers. 5. Po was increased after superfusion of the cytoplasmic membrane surface with the active catalytic subunit of cyclic AMP-dependent protein kinase (PK-A), together with MgATP. Phosphorylation altered the distribution of channel closed times but had little effect on open times. The results suggest that phosphorylation is an important molecular mechanism in modulating the activity of this KCa channel from mammalian brain.

scholarly journals Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Joanna M Dragich ◽  
Takaaki Kuwajima ◽  
Megumi Hirose-Ikeda ◽  
Michael S Yoon ◽  
Evelien Eenjes ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Axon Guidance ◽  
Mouse Genetics ◽  
Mammalian Brain ◽  
Complex Cell ◽  
Neuronal Connectivity ◽  
Molecular Scaffold ◽  
Evolutionarily Conserved ◽  
Brain And Spinal Cord ◽  
The Brain

The regulation of protein degradation is essential for maintaining the appropriate environment to coordinate complex cell signaling events and to promote cellular remodeling. The Autophagy linked FYVE protein (Alfy), previously identified as a molecular scaffold between the ubiquitinated cargo and the autophagic machinery, is highly expressed in the developing central nervous system, indicating that this pathway may have yet unexplored roles in neurodevelopment. To examine this possibility, we used mouse genetics to eliminate Alfy expression. We report that this evolutionarily conserved protein is required for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Consistent with a phenotype reflecting a failure in axon guidance, the loss of Alfy in mice disrupts localization of glial guidepost cells, and attenuates axon outgrowth in response to Netrin-1. These findings further support the growing indication that macroautophagy plays a key role in the developing CNS.

scholarly journals Regeneration and Plasticity in the Brain and Spinal Cord

2007 ◽  
Vol 27 (8) ◽  
pp. 1417-1430 ◽  
Author(s):  
Barbro B Johansson
Keyword(s):  
Spinal Cord ◽  
Progenitor Cells ◽  
Subventricular Zone ◽  
Cortical Neurons ◽  
Brain Plasticity ◽  
Brain Lesions ◽  
Mammalian Brain ◽  
Long Distance ◽  
Inhibitory Factors ◽  
The Brain

The concept of brain plasticity covers all the mechanisms involved in the capacity of the brain to adjust and remodel itself in response to environmental requirements, experience, skill acquisition, and new challenges including brain lesions. Advances in neuroimaging and neurophysiologic techniques have increased our knowledge of task-related changes in cortical representation areas in the intact and injured human brain. The recognition that neuronal progenitor cells proliferate and differentiate in the subventricular zone and dentate gyrus in the adult mammalian brain has raised the hope that regeneration may be possible after brain lesions. Regeneration will require that new cells differentiate, survive, and integrate into existing neural networks and that axons regenerate. To what extent this will be possible is difficult to predict. Current research explores the possibilities to modify endogenous neurogenesis and facilitate axonal regeneration using myelin inhibitory factors. After apoptotic damage in mice new cortical neurons can form long-distance connections. Progenitor cells from the subventricular zone migrate to cortical and subcortical regions after ischemic brain lesions, apparently directed by signals from the damaged region. Postmortem studies on human brains suggest that neurogenesis may be altered in degenerative diseases. Functional and anatomic data indicate that myelin inhibitory factors, cell implantation, and modification of extracellular matrix may be beneficial after spinal cord lesions. Neurophysiologic data demonstrating that new connections are functioning are needed to prove regeneration. Even if not achieving the goal, methods aimed at regeneration can be beneficial by enhancing plasticity in intact brain regions.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

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