Pharmacological Studies on the Auditory Synapses in a Grasshopper

1961 ◽  
Vol 38 (4) ◽  
pp. 759-770
Author(s):  
NOBUO SUGA ◽  
YASUJI KATSUKI
Keyword(s):  
Inhibitory Effect ◽  
Inhibitory Synapses ◽  
Inhibitory Interneurons ◽  
Excitatory Synapses ◽  
Nerve Fibres ◽  
Inhibitory Interaction ◽  
Natural Activity ◽  
Pharmacological Studies ◽  
Prothoracic Ganglion ◽  
Large Fibre

1. Picrotoxin, eserin, butyrylcholine and acetylcholine bring about increase of impulse discharges on the T large fibre in the cord. Picrotoxin gives conspicuous increase of impulse discharges in the response of the T large fibres to sound, while the excitatory effects of the latter three agents are not so conspicuous. 2. Such effects can be explained on the assumption that picrotoxin inhibits the inhibitory synapses, so that the T large fibre is fully activated by both tympanic nerves, while the latter three agents activate both the excitatory and inhibitory fibres. 3. GABA, γ-aminobutyrylcholine and D-tubocurarine act reversibly as inhibitors of the activity of the T large fibre. The response evoked in the T large fibre may be suppressed by the activities of the inhibitory interneurons activated by the tympanic nerve fibres. 4. After the application of picrotoxin solution to the prothoracic ganglion the threshold of the T large fibre near to a sound source rises while that of the opposite side falls. The inhibitory effect seems to be eliminated by the drug action and the T large fibre is activated by both the ipsilateral and the contralateral excitatory fibres. 5. The increased information about a source of sound which arises from the central inhibitory interaction is disturbed by the application of picrotoxin. 6. The conclusion that the T large fibre has excitatory synapses with the tympanic nerves, and inhibitory synapses with the inhibitory interneurons activated by the tympanic neurons, has been confirmed pharmacologically. 7. The inhibitory interneurons are activated not only by the natural activity of the tympanic nerve, but also by activity elicited electrically with square pulses.

Central Mechanism of Hearing in Insects

1961 ◽  
Vol 38 (3) ◽  
pp. 545-558 ◽  
Author(s):  
NOBUO SUGA ◽  
YASUJI KATSUKI
Keyword(s):  
Sound Source ◽  
Threshold Curve ◽  
Inhibitory Interaction ◽  
Response Range ◽  
Metathoracic Ganglion ◽  
Hair Sensilla ◽  
Prothoracic Ganglion ◽  
Tympanic Organ ◽  
Large Fibre ◽  
The Brain

1. The impulses from the tympanic organ are transmitted at the prothoracic ganglion to a central neuron, the auditory T large fibre, which lies in the cord between the brain and the metathoracic ganglion. The impulses in the T large fibre are conducted rostrally and caudally with the same discharge pattern. Information is sent up to the brain, and down to the metathoracic ganglion, after a delay of about 12 msec. 2. The impulses from the cercal hair sensilla are transmitted to two similar auditory C large fibres which lie in the cord between the metathoracic and last (6th) abdominal ganglia and are then sent up to the mesothoracic ganglia by other auditory large fibres. 3. Central inhibitory interaction between the impulses from the tympanic nerves of the two sides are shown by a marked increase of impulses in the T large fibre following section of one of the tympanic nerves. No inhibitory interaction is found between the impulses from the two cercal nerves. 4. The auditory T large fibre receives not only the excitatory effect from the ipsilateral tympanic nerve at the prothoracic ganglion, but also the inhibitory and weak excitatory effects from the contralateral one. 5. The response range of the T large fibre is narrower than the threshold curve of the tympanic nerve and corresponds with one type of response range in the tympanic neurons. The response ranges of the C large fibres correspond closely with the threshold curve of the cercal nerve. 6. A large difference in threshold between the two T large fibres is found in the response to sound incident from the side. The number of impulses in the T large fibre nearer to the sound source is greater than in that farther from the source. 7. The difference in the number of impulses between the two T large fibres is most marked in the response to sound of the frequency which is dominant in stridulation. This difference is due to the mutual inhibitory interaction of neurons which modifies the number of impulses without changing the threshold of the tympanic large fibre. 8. It is suggested that the central inhibitory interaction increases the information about a sound source and plays an important role in the mechanism of the directional sense. 9. The stridulation of the group activates the tympanic nerve and evokes synchronized discharge in the T large fibre, but scarcely at all in the primary C large fibre. The tympanic organ and its neural network seem well adapted to reception of stridulation. 10. It is concluded that though neither of the two sound receptive organs--the tympanic organ and the cercal hair sensilla--can perform frequency analysis, the insect may be able to do so by making use of both organs, since they have different frequency ranges and are served by different auditory large-fibre tracts.

Organization and Plasticity of Cortical Inhibition

2017 ◽  
Author(s):  
Bernard Kripkee ◽  
Robert C. Froemke
Keyword(s):  
Neural Activity ◽  
Cortical Inhibition ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Inhibitory Synapses ◽  
Inhibitory Interneurons ◽  
Excitatory Synapses ◽  
Different Types ◽  
Inhibitory Plasticity

Plasticity of inhibitory synapses keeps inhibition in balance and in register with excitation when changes occur in excitatory synapses. Inhibition has many functions to perform, and there are many kinds of inhibitory neurons to perform various computations and regulate network activity. Different forms of long-term changes in inhibitory synapses have been demonstrated that depend on neural activity. Inhibitory plasticity appears to be partly responsible for the specificity of the inhibitory connections needed to carry out some inhibitory functions. The evolving story of cortical inhibitory plasticity shows that different types of inhibitory interneurons play different roles in a variety of inhibitory functions, that several types of inhibitory plasticity have been attested, and that different forms of plasticity can be expected to have different effects on the organization and specificity of inhibitory connections.

Mechanism of the Antiplatelet Action of Dipyridamole in Whole Blood: Modulation of Adenosine Concentration and Activity

1986 ◽  
Vol 55 (01) ◽  
pp. 012-018 ◽  
Author(s):  
Paolo Gresele ◽  
Jef Arnout ◽  
Hans Deckmyn ◽  
Jos Vermylen
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Receptor ◽  
Whole Blood ◽  
Blood Cells ◽  
Inhibitory Action ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Adenosine Concentration ◽  
Pharmacological Studies

SummaryDipyridamole inhibits platelet aggregation in whole blood at lower concentrations than in plasma. The blood cells responsible for increased effectiveness in blood are the erythrocytes. Using the impedance aggregometer we have carried out a series of pharmacological studies in vitro to elucidate the mechanism of action of dipyridamole in whole blood. Adenosine deaminase, an enzyme breaking down adenosine, reverses the inhibitory action of dipyridamole. Two different adenosine receptor antagonists, 5’-deoxy-5’-methylthioadenosine and theophylline, also partially neutralize the activity of dipyridamole in blood. Enprofylline, a phosphodiesterase inhibitor with almost no adenosine receptor antagonistic properties, potentiates the inhibition of platelet aggregation by dipyridamole. An inhibitory effect similar to that of dipyridamole can be obtained combining a pure adenosine uptake inhibitor (RE 102 BS) with a pure phosphodiesterase inhibitor (MX-MB 82 or enprofylline). Mixing the blood during preincubation with dipyridamole increases the degree of inhibition. Lowering the haematocrit slightly reduces the effectiveness.Although we did not carry out direct measurements of adenosine levels, the results of our pharmacological studies clearly show that dipyridamole inhibits platelet aggregation in whole blood by blocking the reuptake of adenosine formed from precursors released by red blood cells following microtrauma. Its slight phosphodiesterase inhibitory action potentiates the effects of adenosine on platelets.

Both M1 and M3 receptors regulate exocrine secretion by mucous acini

1996 ◽  
Vol 271 (6) ◽  
pp. C1963-C1972 ◽  
Author(s):  
D. J. Culp ◽  
W. Luo ◽  
L. A. Richardson ◽  
G. E. Watson ◽  
L. R. Latchney
Keyword(s):  
Inhibitory Effect ◽  
Exocrine Secretion ◽  
Muscarinic Agonist ◽  
High Affinity ◽  
Muscarinic Response ◽  
M1 Receptor ◽  
M3 Receptors ◽  
Pharmacological Studies ◽  
Equilibrium Dissociation

We investigated the role of M1 and M3 receptors in regulating exocrine secretion from acini isolated from rat sublingual glands. In secretion experiments, we derived affinity values (KB) from Schild regression analysis for the antagonists pirenzepine (61.0 nM) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP; 1.06 nM). The KB for 4-DAMP is similar to its affinity value [equilibrium dissociation constant from competition studies (Ki); 1.81 nM] determined from radioligand competition experiments. In contrast, the KB for pirenzepine is between its high-affinity (17.6 nM) and low-affinity (404 nM) Ki values. In separate secretion experiments, we found that the M1 receptor antagonist, M1-toxin, induces a rightward shift in the concentration-response curve to muscarinic agonist and inhibits maximal secretion by 40%. The inhibitory effect of M1-toxin appears specific for M1 receptor blockade, since the toxin abolishes acinar high-affinity pirenzepine-binding sites and does not inhibit secretion induced by nonmuscarinic agents. Additional pharmacological studies indicate muscarinic receptors do not function through putative neural elements within isolated acini. Our combined results are consistent with both M1 and M3 receptors directly regulating mucous acinar exocrine secretion and indicate M3 receptors alone are insufficient to induce a maximal muscarinic response.

Electrophysiological evidence from glutamate microapplications for local excitatory circuits in the CA1 area of rat hippocampal slices

1988 ◽  
Vol 59 (1) ◽  
pp. 110-123 ◽  
Author(s):  
E. P. Christian ◽  
F. E. Dudek
Keyword(s):  
Hippocampal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Inhibitory Synapses ◽  
Excitatory Synapses ◽  
Recording Site ◽  
Postsynaptic Potentials ◽  
Inhibitory Postsynaptic Potentials ◽  
Ca1 Area ◽  
Transverse Slice

1. Evidence for local excitatory synaptic connections in CA1 of the rat hippocampus was obtained by recording excitatory postsynaptic potentials (EPSPs) intracellularly from pyramidal cells during local microapplications of glutamate. 2. Experiments were performed in hippocampal slices cut parallel to (transverse slice) or perpendicular to (longitudinal slice) alvear fibers. In normal solutions, glutamate microdrops (10–20 mM, 10–20 micron diam) applied in CA1 within 400 micron of recorded cells sometimes increased the frequency of inhibitory postsynaptic potentials for 5–10 s in both transverse and longitudinal slices. Increases in EPSP frequency were also occasionally observed, but only in transverse slices. Tetrodotoxin (1 microgram/ml) blocked glutamate-induced increases in PSP frequency, thus indicating that they were not caused by subthreshold effects on presynaptic terminals. Increases in PSP frequency were interpreted to result from glutamate activation of hippocampal neurons with inhibitory and excitatory connections to recorded neurons. 3. In both slice orientations, local excitatory circuits were studied in more isolated conditions by surgically separating CA1 from CA3 (transverse slices) and by blocking GABAergic inhibitory synapses with picrotoxin (5–10 microM). Microdrops were systematically applied at 200 and 400 micron on each side of the recording site. Significant glutamate-induced increases in EPSP frequency were observed in neurons from both slice orientations to microdrops in at least one of the locations. This provided evidence that excitatory synapses are present in both transverse and longitudinal slices. 4. Substantial increases in EPSP frequency only occurred in neurons from longitudinal slices when glutamate was microapplied 200 micron or less from the recording site. In transverse slices, however, large increases in EPSP frequency were observed to glutamate microapplications at 200 or 400 micron. These data suggest that CA1 local excitatory connections project for longer distances in the transverse than in the longitudinal plane of section. 5. Increases in EPSP frequency, averaged across cells, did not differ significantly in the four microapplication sites in either transverse or longitudinal slices. Thus local excitation in CA1 does not appear to be asymmetrically arranged in the way suggested for CA3. 6. The densities of local excitatory circuits in CA1 versus CA3 were studied by quantitatively comparing glutamate-induced increases in EPSP frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses

2008 ◽  
Vol 105 (40) ◽  
pp. 15581-15586 ◽  
Author(s):  
Angharad M. Kerr ◽  
Ellen Reisinger ◽  
Peter Jonas
Keyword(s):  
Transmitter Release ◽  
Granule Cells ◽  
Inhibitory Synapses ◽  
Pcr Analysis ◽  
Excitatory Synapses ◽  
Postsynaptic Currents ◽  
Reverse Transcription Quantitative Pcr ◽  
Synaptotagmin 1 ◽  
Organotypic Slice Cultures ◽  
Inhibitory Transmitter

Previous studies revealed that synaptotagmin 1 is the major Ca2+ sensor for fast synchronous transmitter release at excitatory synapses. However, the molecular identity of the Ca2+ sensor at hippocampal inhibitory synapses has not been determined. To address the functional role of synaptotagmin 1 at identified inhibitory terminals, we made paired recordings from synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus in organotypic slice cultures from wild-type and synaptotagmin 1-deficient mice. As expected, genetic elimination of synaptotagmin 1 abolished synchronous transmitter release at excitatory GC–BC synapses. However, synchronous release at inhibitory BC–GC synapses was maintained. Quantitative analysis revealed that elimination of synaptotagmin 1 reduced release probability and depression but maintained the synchrony of transmitter release at BC–GC synapses. Elimination of synaptotagmin 1 also increased the frequency of both miniature excitatory postsynaptic currents (measured in BCs) and miniature inhibitory postsynaptic currents (recorded in GCs), consistent with a clamping function of synaptotagmin 1 at both excitatory and inhibitory terminals. Single-cell reverse-transcription quantitative PCR analysis revealed that single BCs coexpressed multiple synaptotagmin isoforms, including synaptotagmin 1–5, 7, and 11–13. Our results indicate that, in contrast to excitatory synapses, synaptotagmin 1 is not absolutely required for synchronous release at inhibitory BC–GC synapses. Thus, alternative fast Ca2+ sensors contribute to synchronous release of the inhibitory transmitter GABA in cortical circuits.

scholarly journals Synaptic phospholipids as a new target for cortical hyperexcitability and E/I balance in psychiatric disorders

2018 ◽  
Vol 23 (8) ◽  
pp. 1699-1710 ◽  
Author(s):  
Carine Thalman ◽  
Guilherme Horta ◽  
Lianyong Qiao ◽  
Heiko Endle ◽  
Irmgard Tegeder ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Cortical Excitability ◽  
Sensory Information ◽  
Inhibitory Synapses ◽  
Excitatory Synapses ◽  
Glutamatergic Transmission ◽  
Cortical Hyperexcitability ◽  
Sensory Information Processing ◽  
Novel Drug ◽  
General Method

Summary Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses. This ATX sorting, as well as the enzymatic activity of astrocyte-derived ATX are dynamically regulated by neuronal activity via astrocytic glutamate receptors. Pharmacological and genetic ATX inhibition both rescued schizophrenia-related hyperexcitability syndromes caused by altered bioactive lipid signaling in two genetic mouse models for psychiatric disorders. Interestingly, ATX inhibition did not affect naive animals. However, as our data suggested that pharmacological ATX inhibition is a general method to reverse cortical excitability, we applied ATX inhibition in a ketamine model of schizophrenia and rescued thereby the electrophysiological and behavioral schizophrenia-like phenotype. Our data show that astrocytic ATX is a novel modulator of glutamatergic transmission and that targeting ATX might be a versatile strategy for a novel drug therapy to treat cortical hyperexcitability in psychiatric disorders.

scholarly journals Multifaceted Changes in Synaptic Composition and Astrocytic Involvement in a Mouse Model of Fragile X Syndrome

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anish K. Simhal ◽  
Yi Zuo ◽  
Marc M. Perez ◽  
Daniel V. Madison ◽  
Guillermo Sapiro ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fragile X Syndrome ◽  
Knockout Mouse ◽  
Fragile X ◽  
Inhibitory Synapses ◽  
Excitatory Synapses ◽  
Array Tomography ◽  
Layer 4 ◽  
Fmr1 Knockout Mouse ◽  
Circuit Function

Abstract Fragile X Syndrome (FXS), a common inheritable form of intellectual disability, is known to alter neocortical circuits. However, its impact on the diverse synapse types comprising these circuits, or on the involvement of astrocytes, is not well known. We used immunofluorescent array tomography to quantify different synaptic populations and their association with astrocytes in layers 1 through 4 of the adult somatosensory cortex of a FXS mouse model, the FMR1 knockout mouse. The collected multi-channel data contained approximately 1.6 million synapses which were analyzed using a probabilistic synapse detector. Our study reveals complex, synapse-type and layer specific changes in the neocortical circuitry of FMR1 knockout mice. We report an increase of small glutamatergic VGluT1 synapses in layer 4 accompanied by a decrease in large VGluT1 synapses in layers 1 and 4. VGluT2 synapses show a rather consistent decrease in density in layers 1 and 2/3. In all layers, we observe the loss of large inhibitory synapses. Lastly, astrocytic association of excitatory synapses decreases. The ability to dissect the circuit deficits by synapse type and astrocytic involvement will be crucial for understanding how these changes affect circuit function, and ultimately defining targets for therapeutic intervention.

scholarly journals Interaction between autism-linked MDGAs and neuroligins suppresses inhibitory synapse development

2013 ◽  
Vol 200 (3) ◽  
pp. 321-336 ◽  
Author(s):  
Katherine L. Pettem ◽  
Daisaku Yokomaku ◽  
Hideto Takahashi ◽  
Yuan Ge ◽  
Ann Marie Craig
Keyword(s):  
Neurodevelopmental Disorders ◽  
Hippocampal Neurons ◽  
Rare Variants ◽  
Inhibitory Synapse ◽  
Excitatory Synapse ◽  
Inhibitory Synapses ◽  
Excitatory Synapses ◽  
Synapse Development ◽  
Multiple Protein ◽  
Synapse Density

Rare variants in MDGAs (MAM domain–containing glycosylphosphatidylinositol anchors), including multiple protein-truncating deletions, are linked to autism and schizophrenia, but the function of these genes is poorly understood. Here, we show that MDGA1 and MDGA2 bound to neuroligin-2 inhibitory synapse–organizing protein, also implicated in neurodevelopmental disorders. MDGA1 inhibited the synapse-promoting activity of neuroligin-2, without altering neuroligin-2 surface trafficking, by inhibiting interaction of neuroligin-2 with neurexin. MDGA binding and suppression of synaptogenic activity was selective for neuroligin-2 and not neuroligin-1 excitatory synapse organizer. Overexpression of MDGA1 in cultured rat hippocampal neurons reduced inhibitory synapse density without altering excitatory synapse density. Furthermore, RNAi-mediated knockdown of MDGA1 selectively increased inhibitory but not excitatory synapse density. These results identify MDGA1 as one of few identified negative regulators of synapse development with a unique selectivity for inhibitory synapses. These results also place MDGAs in the neurexin–neuroligin synaptic pathway implicated in neurodevelopmental disorders and support the idea that an imbalance between inhibitory and excitatory synapses may contribute to these disorders.

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