scholarly journals The Molecular Logic Organizing the Functional Compartmentalization of Reciprocal Synapses

2021 ◽  
Author(s):  
Cosmos Yuqi Wang ◽  
Justin H. Trotter ◽  
Kif Liakath-Ali ◽  
Sung-jin Lee ◽  
Xinran Liu ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Granule Cells ◽  
Protein Complexes ◽  
Interaction Network ◽  
Mitral Cell ◽  
Mitral Cells ◽  
Molecular Logic ◽  
Organizational Principle ◽  
Cis Interaction ◽  
Dendrodendritic Synapses

Reciprocal synapses are formed by neighboring dendritic processes that create the smallest possible neural circuit. Reciprocal synapses are widespread in brain and essential for information processing, but constitute a conceptual conundrum: How are adjacent pre- and post synaptic specializations maintained as separate functional units? Here, we reveal an organizational principle for reciprocal synapses, using dendrodendritic synapses between mitral and granule cells in the mouse olfactory bulb as a paradigm. We show that mitral cells secrete cerebellin-1 to block the cis-interaction of mitral cell neurexins with neuroligins, thereby enabling their separate trans-interactions. Ablating either cerebellin-1 or neuroligins in mitral cells severely impaired granule cell→mitral cell synapses, as did overexpression of postsynaptic neurexins that form ciscomplexes with neuroligins, but not of mutant neurexins unable to bind to neuroligins. Our data uncover a cis/trans-protein interaction network as a general design principle that organizes reciprocal dendro dendritic synapses by compartmentalizing neurexin-based trans-synaptic protein complexes.

Group I Metabotropic Glutamate Receptors Are Differentially Expressed by Two Populations of Olfactory Bulb Granule Cells

2007 ◽  
Vol 97 (4) ◽  
pp. 3136-3141 ◽  
Author(s):  
Thomas Heinbockel ◽  
Kathryn A. Hamilton ◽  
Matthew Ennis
Keyword(s):  
Olfactory Bulb ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Granule Cells ◽  
Mitral Cell ◽  
Mitral Cells ◽  
Patch Clamp Recording ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Bath Application

In the main olfactory bulb, several populations of granule cells (GCs) can be distinguished based on the soma location either superficially, interspersed with mitral cells within the mitral cell layer (MCL), or deeper, within the GC layer (GCL). Little is known about the physiological properties of superficial GCs (sGCs) versus deep GCs (dGCs). Here, we used patch-clamp recording methods to explore the role of Group I metabotropic glutamate receptors (mGluRs) in regulating the activity of GCs in slices from wildtype and mGluR−/− mutant mice. In wildtype mice, bath application of the selective Group I mGluR agonist DHPG depolarized and increased the firing rate of both GC subtypes. In the presence of blockers of fast synaptic transmission (APV, CNQX, gabazine), DHPG directly depolarized both GC subtypes, although the two GC subtypes responded differentially to DHPG in mGluR1−/− and mGluR5−/− mice. DHPG depolarized sGCs in slices from mGluR5−/− mice, although it had no effect on sGCs in slices from mGluR1−/− mice. By contrast, DHPG depolarized dGCs in slices from mGluR1−/− mice but had no effect on dGCs in slices from mGluR5−/− mice. Previous studies showed that mitral cells express mGluR1 but not mGluR5. The present results therefore suggest that sGCs are more similar to mitral cells than dGCs in terms of mGluR expression.

The Mitral and Short Axon Cells of the Olfactory Bulb

1970 ◽  
Vol 7 (3) ◽  
pp. 631-651
Author(s):  
J. L. PRICE ◽  
T. P. S. POWELL
Keyword(s):  
Electron Microscope ◽  
Olfactory Bulb ◽  
Granule Cells ◽  
Primary Dendrite ◽  
Plexiform Layer ◽  
Mitral Cell ◽  
Granule Cell Layer ◽  
Mitral Cells ◽  
Axon Initial Segments ◽  
Large Neurons

A description is given of the mitral and short axon cells of the olfactory bulb of the rat from Golgi material examined with the light microscope and from material examined with the electron microscope. The mitral cells are large neurons with primary and secondary dendrites which both extend into the overlying external plexiform layer, although only the primary dendrite enters the glomerular formations. No predominant antero-posterior orientation of the secondary dendrites has been found. Within the glomeruli the mitral cell dendrites are in synaptic contact with the olfactory nerves and also with the periglomerular cells, but elsewhere the only synapses on the mitral cells are the ‘reciprocal synapses’ with the granule cells. Synaptic-type vesicles are found in all parts of the mitral cells, including the axon initial segments; they appear to be especially concentrated in the distal portions of the dendrites. Several types of short axon cells have been found in the granule cell layer in Golgi-impregnated material. Their cell bodies can also be distinguished with the electron microscope, and from previous work it is probable that the axons of at least some of these cells form flattened-vesicle symmetrical synapses upon the granule cells.

Flash Photolysis Reveals a Diversity of Ionotropic Glutamate Receptors on the Mitral Cell Somatodendritic Membrane

2003 ◽  
Vol 90 (3) ◽  
pp. 1737-1746 ◽  
Author(s):  
Graeme Lowe
Keyword(s):  
Glutamate Receptors ◽  
Gaba Receptors ◽  
Granule Cells ◽  
Flash Photolysis ◽  
Competitive Inhibition ◽  
Synaptic Cleft ◽  
Mitral Cell ◽  
Transmission Model ◽  
Wide Field ◽  
Mitral Cells

It is widely held that the soma and basal dendrites of olfactory bulb mitral cells receive exclusively inhibitory synaptic input from local interneurons. However, the mitral somatodendritic membrane exhibits immunoreactivity for a variety of glutamate receptors, and blocking GABA receptors unmasks mitral cell self-excitation. This excitation is proposed to be mediated either by diffuse spillover of the mitral cells' own released glutamate, or by punctate transmission from glutamate-releasing granule cells. This study examined the pharmacology and kinetics of glutamate sensitivity of mitral cells by flash photolysis of nitroindoline caged glutamates, which facilitate reliable activation of receptors in the synaptic cleft. Wide-field laser uncaging (3.5-ms flash) of approximately 0.5–1 mM glutamate onto the soma activated large currents with fast (3.4-ms rise, 7.5-ms decay) and slow (64-ms rise, >10-s decay) components. In 100 μM APV, slow currents were reduced to 53% of control (257-ms rise, 2-s decay), displayed outward rectification in 1.3 mM Mg2+, and blocked by 15 μM 5,7-dichlorokynurenate. Responses to ≲100 μM glutamate were fully antagonized by 100 μM APV, consistent with competitive inhibition at high-affinity NMDA receptors. An APV-resistant NMDA receptor was not observed, refuting the punctate transmission model. Fast currents were blocked by 10 μM NBQX, boosted 3.28-fold by 100 μM cyclothiazide, and resolved into AMPA (40%) and kainate (60%) receptor components by 100 μM SYM2206. The results suggest that self-excitation depends on AMPA, kainite, and conventional NMDA autoreceptors on the mitral cell.

Dendrodendritic Inhibition and Simulated Odor Responses in a Detailed Olfactory Bulb Network Model

2003 ◽  
Vol 90 (3) ◽  
pp. 1921-1935 ◽  
Author(s):  
Andrew P. Davison ◽  
Jianfeng Feng ◽  
David Brown
Keyword(s):  
Experimental Data ◽  
Spatial Distribution ◽  
Olfactory Bulb ◽  
Time Course ◽  
Granule Cells ◽  
Temporal Structure ◽  
Network Connectivity ◽  
Realistic Model ◽  
Mitral Cells ◽  
Dendrodendritic Synapses

In the olfactory bulb, both the spatial distribution and the temporal structure of neuronal activity appear to be important for processing odor information, but it is currently impossible to measure both of these simultaneously with high resolution and in all layers of the bulb. We have developed a biologically realistic model of the mammalian olfactory bulb, incorporating the mitral and granule cells and the dendrodendritic synapses between them, which allows us to observe the network behavior in detail. The cell models were based on previously published work. The attributes of the synapses were obtained from the literature. The pattern of synaptic connections was based on the limited experimental data in the literature on the statistics of connections between neurons in the bulb. The results of simulation experiments with electrical stimulation agree closely in most details with published experimental data. This gives confidence that the model is capturing features of network interactions in the real olfactory bulb. The model predicts that the time course of dendrodendritic inhibition is dependent on the network connectivity as well as on the intrinsic parameters of the synapses. In response to simulated odor stimulation, strongly activated mitral cells tend to suppress neighboring cells, the mitral cells readily synchronize their firing, and increasing the stimulus intensity increases the degree of synchronization. Preliminary experiments suggest that slow temporal changes in the degree of synchronization are more useful in distinguishing between very similar odorants than is the spatial distribution of mean firing rate.

SK Channel Regulation of Dendritic Excitability and Dendrodendritic Inhibition in the Olfactory Bulb

2005 ◽  
Vol 94 (6) ◽  
pp. 3743-3750 ◽  
Author(s):  
Brady J. Maher ◽  
Gary L. Westbrook
Keyword(s):  
Olfactory Bulb ◽  
Granule Cells ◽  
Brain Slices ◽  
Mitral Cell ◽  
Mitral Cells ◽  
Sk Channels ◽  
Action Potential Firing ◽  
Sk Channel ◽  
Dendritic Excitability ◽  
Potential Firing

Small-conductance calcium-activated potassium channels (SK) regulate dendritic excitability in many neurons. In the olfactory bulb, regulation of backpropagating action potentials and dendrodendritic inhibition depend on the dendritic excitability of mitral cells. We report here that SK channel currents are present in mitral cells but are not detectable in granule cells in the olfactory bulb. In brain slices from PND 14–21 mice, long step depolarizations (100 ms) in the mitral cell soma evoked a cadmium- and apamin-sensitive outward SK current lasting several hundred milliseconds. Block of the SK current unmasked an inward N-methyl-d-aspartate (NMDA) autoreceptor current due to glutamate released from mitral cell dendrites. In low extracellular Mg2+ (100 μM), brief step depolarizations (2 ms) evoked an apamin-sensitive current that was reduced by d,l-2-amino-5-phosphonopentanoic acid. In current- clamp, block of SK channels increased action potential firing in mitral cells as well as dendrodendritic inhibition. Our results indicate that SK channels can be activated either by calcium channels or NMDA channels in mitral cell dendrites, providing a mechanism for local control of dendritic excitability.

Synaptic Organization and Neurotransmitters in the Rat Accessory Olfactory Bulb

1999 ◽  
Vol 81 (1) ◽  
pp. 345-355 ◽  
Author(s):  
Changping Jia ◽  
Wei R. Chen ◽  
Gordon M. Shepherd
Keyword(s):  
Olfactory Bulb ◽  
Granule Cells ◽  
Mitral Cell ◽  
Activity Period ◽  
Mitral Cells ◽  
Accessory Olfactory Bulb ◽  
Field Potentials ◽  
Synaptic Organization ◽  
Evoked Field Potentials ◽  
Stimulation Of

Jia, Changping, Wei R. Chen, and Gordon M. Shepherd. Synaptic organization and neurotransmitters in the rat accessory olfactory bulb. J. Neurophysiol. 81: 345–355, 1999. The accessory olfactory bulb (AOB) is the first relay station in the vomeronasal system and may play a critical role in processing pheromone signals. The AOB shows similar but less distinct lamination compared with the main olfactory bulb (MOB). In this study, synaptic organization of the AOB was analyzed in slice preparations from adult rats by using both field potential and patch-clamp recordings. Stimulation of the vomeronasal nerve (VN) evoked field potentials that showed characteristic patterns in different layers of the AOB. Current source density (CSD) analysis of the field potentials revealed spatiotemporally separated loci of inward current (sinks) that represented sequential activation of different neuronal components: VN activity (period I), synaptic excitation of mitral cell apical dendrites (period II), and activation of granule cells by mitral cell basal dendrites (period III). Stimulation of the lateral olfactory tract also evoked field potentials in the AOB, which indicated antidromic activation of the mitral cells (period I and II) followed by activation of granule cells (period III). Whole cell patch recordings from mitral and granule cells of the AOB supported that mitral cells are excited by VN terminals and subsequently activate granule cells through dendrodendritic synapses. Both CSD analysis and patch recordings provided evidence that glutamate is the neurotransmitter at the vomeronasal receptor neuron; mitral cell synapses and both NMDA and non-NMDA receptors are involved. We also demonstrated electrophysiologically that reciprocal interaction between mitral and granule cells in the AOB is through the dendrodendritic reciprocal synapses. The neurotransmitter at the mitral-to-granule synapses is glutamate and at the granule-to-mitral synapse is γ-aminobutyric acid. The synaptic interactions among receptor cell terminals, mitral cells, and granule cells in the AOB are therefore similar to those in the MOB, suggesting that processing of chemosensory information in the AOB shares similarities with that in the MOB.

γ-Frequency Excitatory Input to Granule Cells Facilitates Dendrodendritic Inhibition in the Rat Olfactory Bulb

2003 ◽  
Vol 90 (2) ◽  
pp. 644-654 ◽  
Author(s):  
Brian Halabisky ◽  
Ben W. Strowbridge
Keyword(s):  
Olfactory Bulb ◽  
Nmda Receptors ◽  
Lateral Inhibition ◽  
Granule Cells ◽  
Critical Role ◽  
Recurrent Inhibition ◽  
Granule Cell Layer ◽  
Gabaergic Interneurons ◽  
Mitral Cells ◽  
Dendrodendritic Synapses

Recurrent and lateral inhibition play a prominent role in patterning the odor-evoked discharges in mitral cells, the output neurons of the olfactory bulb. Inhibitory responses in this brain region are mediated through reciprocal synaptic connections made between the dendrites of mitral cells and GABAergic interneurons. Previous studies have demonstrated that N-methyl-d-aspartate (NMDA) receptors on interneurons play a critical role in eliciting GABA release at reciprocal dendrodendritic synapses. In acute olfactory bulb slices, these receptors are tonically blocked by extracellular Mg2+, and recurrent inhibition is disabled. In the present study, we examined the mechanisms by which this tonic blockade could be reversed. We demonstrate that near-coincident activation of an excitatory pathway to the proximal dendrites of GABAergic interneurons relieves the Mg2+ blockade of NMDA receptors at reciprocal dendrodendritic synapses and greatly facilitates recurrent inhibition onto mitral cells. Gating of recurrent and lateral inhibition in the presence of extracellular Mg2+ requires γ-frequency stimulation of glutamatergic axons in the granule cell layer. Long-range excitatory axon connections from mitral cells innervated by different subpopulations of olfactory receptor neurons may provide a gating input to granule cells, thereby facilitating the mitral cell lateral inhibition that contributes to odorant encoding.

scholarly journals Odour discrimination in the olfactory bulb of goldfish: contrasting interactions between mitral cells and ruffed cells

2000 ◽  
Vol 355 (1401) ◽  
pp. 1229-1232 ◽  
Author(s):  
H. P. Zippel ◽  
M. Gloger ◽  
S. Nasser ◽  
S. Wilcke
Keyword(s):  
Granule Cells ◽  
Cell Activity ◽  
Plexiform Layer ◽  
Mitral Cell ◽  
Mitral Cells ◽  
Cell Potential ◽  
Tungsten Microelectrode ◽  
Odour Discrimination ◽  
Receptor Neurons ◽  
Familiar Stimuli

Anatomical differences characterizing mitral cells and ruffed cells have been published by T. Kosaka and K. Hama in three teleost species. Physiological responses from both types of relay neurons were recorded extracellularly and simultaneously in the plexiform layer, using a single tungsten microelectrode. During interstimulus intervals mitral cells responded with higher, frequently burst-like impulse rates triggered by the activity of epithelial receptor neurons. Mitral cell activity could be totally suppressed by local anaesthesia of the olfactory epithelium. Ruffed cell impulse rates were low, and each action potential triggered a long-lasting (3-5 ms), continuously varying, summed granule cell potential. During olfactory stimulation with non-familiar stimuli and important biological stimuli such as amino acids, preovulatory and ovulatory pheromones, and a probable alarm pheromone, contrasting interactions between mitral cells and ruffed cells were recorded frequently, which resulted in a drastic intensification of centrally transmitted information. An excitation of mitral cells' activity via granule cells laterally inhibited the ruffed cells' activity, and an inhibition of mitral cells' activity simultaneously ‘released’ an excitation of ruffed cells.

scholarly journals Frequent assembly of chimeric complexes in the protein interaction network of an interspecies yeast hybrid

2020 ◽  
Author(s):  
Rohan Dandage ◽  
Caroline M Berger ◽  
Isabelle Gagnon-Arsenault ◽  
Kyung-Mee Moon ◽  
Richard Greg Stacey ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Molecular Level ◽  
Yeast Species ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Chimeric Protein ◽  
Interaction Network ◽  
Protein Protein Interactions ◽  
Extreme Phenotypes ◽  
Yeast Hybrid

Abstract Hybrids between species often show extreme phenotypes, including some that take place at the molecular level. In this study, we investigated the phenotypes of an interspecies diploid hybrid in terms of protein-protein interactions inferred from protein correlation profiling. We used two yeast species, Saccharomyces cerevisiae and Saccharomyces uvarum, which are interfertile, but yet have proteins diverged enough to be differentiated using mass spectrometry. Most of the protein-protein interactions are similar between hybrid and parents, and are consistent with the assembly of chimeric complexes, which we validated using an orthogonal approach for the prefoldin complex. We also identified instances of altered protein-protein interactions in the hybrid, for instance in complexes related to proteostasis and in mitochondrial protein complexes. Overall, this study uncovers the likely frequent occurrence of chimeric protein complexes with few exceptions, which may result from incompatibilities or imbalances between the parental proteins.

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