scholarly journals Spontaneous activity generated within the olfactory bulb establishes the discrete wiring of mitral cell dendrites

2019 ◽  
Author(s):  
Satoshi Fujimoto ◽  
Marcus N. Leiwe ◽  
Richi Sakaguchi ◽  
Yuko Muroyama ◽  
Reiko Kobayakawa ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Spontaneous Activity ◽  
Neuronal Activity ◽  
Primary Dendrite ◽  
Sensory Information ◽  
Mitral Cell ◽  
Network Activity ◽  
Mitral Cells ◽  
Tufted Cells

ABSTRACTIn the mouse olfactory bulb, sensory information detected by ∼1,000 types of olfactory sensory neurons (OSNs) is represented by the glomerular map. The second-order neurons, mitral and tufted cells, connect a single primary dendrite to one glomerulus. This forms discrete connectivity between the ∼1,000 types of input and output neurons. It has remained unknown how this discrete dendrite wiring is established during development. We found that genetically silencing neuronal activity in mitral cells, but not from OSNs, perturbs the dendrite pruning of mitral cells. In vivo calcium imaging of awake neonatal animals revealed two types of spontaneous neuronal activity in mitral/tufted cells, but not in OSNs. Pharmacological and knockout experiments revealed a role for glutamate and NMDARs. The genetic blockade of neurotransmission among mitral/tufted cells reduced spontaneous activity and perturbed dendrite wiring. Thus, spontaneous network activity generated within the olfactory bulb self-organizes the parallel discrete connections in the mouse olfactory system.

scholarly journals Bursting mitral cells time the oscillatory coupling between olfactory bulb and entorhinal networks in neonatal mice

2020 ◽  
Author(s):  
Johanna K. Kostka ◽  
Sabine Gretenkord ◽  
Ileana L. Hanganu-Opatz
Keyword(s):  
Olfactory Bulb ◽  
Entorhinal Cortex ◽  
Mitral Cell ◽  
Network Activity ◽  
List Type ◽  
Mitral Cells ◽  
Early Postnatal Development ◽  
Theta Phase

ABSTRACTShortly after birth, the olfactory system provides to blind, deaf, non-whisking and motorically-limited rodents not only the main source of environmental inputs, but also the drive boosting the functional entrainment of limbic circuits. However, the cellular substrate of this early communication remains largely unknown. Here we combine in vivo and in vitro patch-clamp and extracellular recordings to reveal the contribution of mitral cell (MC) firing to the early patterns of network activity in the neonatal olfactory bulb (OB) and lateral entorhinal cortex (LEC), the gatekeeper of limbic circuits. We show that MCs predominantly fire either in an irregular bursting or non-bursting pattern during discontinuous theta events in OB. However, the temporal spike-theta phase coupling is stronger for bursting MCs when compared to non-bursting cells. In line with the direct OB projections to LEC, both bursting and non-bursting firing augments during coordinated patterns of entorhinal activity, yet to a higher magnitude for bursting MCs. These cells are stronger temporally coupled to the discontinuous theta events in LEC. Thus, bursting MCs might drive the entrainment of OB-LEC network during neonatal development.KEY POINTSDuring early postnatal development mitral cells show either irregular bursting or non-bursting firing patternsBursting mitral cells preferentially fire during theta bursts in the neonatal OB, being locked to the theta phaseBursting mitral cells preferentially fire during theta bursts in the neonatal lateral entorhinal cortex and are temporally related to both respiration rhythm- and theta phaseBursting mitral cells act as cellular substrate of the olfactory drive promoting the oscillatory entrainment of entorhinal networks

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.

scholarly journals Cellular and Synaptic Mechanisms That Differentiate Mitral Cells and Superficial Tufted Cells Into Parallel Output Channels in the Olfactory Bulb

2020 ◽  
Vol 14 ◽  
Author(s):  
Shelly Jones ◽  
Joel Zylberberg ◽  
Nathan Schoppa
Keyword(s):  
Olfactory Bulb ◽  
Plexiform Layer ◽  
Input Resistance ◽  
Cell Types ◽  
Mitral Cells ◽  
Whole Cell ◽  
Wide Range ◽  
Tufted Cells ◽  
Parallel Output

A common feature of the primary processing structures of sensory systems is the presence of parallel output “channels” that convey different information about a stimulus. In the mammalian olfactory bulb, this is reflected in the mitral cells (MCs) and tufted cells (TCs) that have differing sensitivities to odors, with TCs being more sensitive than MCs. In this study, we examined potential mechanisms underlying the different responses of MCs vs. TCs. For TCs, we focused on superficial TCs (sTCs), which are a population of output TCs that reside in the superficial-most portion of the external plexiform layer, along with external tufted cells (eTCs), which are glutamatergic interneurons in the glomerular layer. Using whole-cell patch-clamp recordings in mouse bulb slices, we first measured excitatory currents in MCs, sTCs, and eTCs following olfactory sensory neuron (OSN) stimulation, separating the responses into a fast, monosynaptic component reflecting direct inputs from OSNs and a prolonged component partially reflecting eTC-mediated feedforward excitation. Responses were measured to a wide range of OSN stimulation intensities, simulating the different levels of OSN activity that would be expected to be produced by varying odor concentrations in vivo. Over a range of stimulation intensities, we found that the monosynaptic current varied significantly between the cell types, in the order of eTC > sTC > MC. The prolonged component was smaller in sTCs vs. both MCs and eTCs. sTCs also had much higher whole-cell input resistances than MCs, reflecting their smaller size and greater membrane resistivity. To evaluate how these different electrophysiological aspects contributed to spiking of the output MCs and sTCs, we used computational modeling. By exchanging the different cell properties in our modeled MCs and sTCs, we could evaluate each property's contribution to spiking differences between these cell types. This analysis suggested that the higher sensitivity of spiking in sTCs vs. MCs reflected both their larger monosynaptic OSN signal as well as their higher input resistance, while their smaller prolonged currents had a modest opposing effect. Taken together, our results indicate that both synaptic and intrinsic cellular features contribute to the production of parallel output channels in the olfactory bulb.

scholarly journals BMPR-2 gates activity-dependent stabilization of dendrites during mitral cell remodeling

2020 ◽  
Author(s):  
Shuhei Aihara ◽  
Satoshi Fujimoto ◽  
Richi Sakaguchi ◽  
Takeshi Imai
Keyword(s):  
Olfactory Bulb ◽  
Neuronal Activity ◽  
Mitral Cell ◽  
In Utero ◽  
Mitral Cells ◽  
Selective Stabilization ◽  
Multiple Primary ◽  
Cell Remodeling ◽  
Developing Neurons ◽  
Activity Dependent

SUMMARYDeveloping neurons initially form excessive neurites and then remodel them based on molecular cues and neuronal activity. Developing mitral cells in the olfactory bulb initially extend multiple primary dendrites. They then stabilize single primary dendrites, while eliminating others. However, the mechanisms underlying the selective dendrite remodeling remain elusive. Using CRISPR/Cas9-based knockout screening combined with in utero electroporation, we identified BMPR-2 as a key regulator for the selective dendrite stabilization. Bmpr2 knockout and its rescue experiments show that BMPR-2 inhibits LIMK without ligands and thereby facilitates dendrite destabilization. In contrast, the overexpression of antagonists and agonists indicate that ligand-bound BMPR-2 stabilizes dendrites, most likely by releasing LIMK. Using genetic and FRET imaging experiments, we also demonstrate that free LIMK is activated by NMDARs via Rac1, facilitating dendrite stabilization through F-actin formation. Thus, the selective stabilization of mitral cell dendrites is ensured by concomitant inputs of BMP ligands and neuronal activity.

scholarly journals Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Mensch ◽  
Jade Dunot ◽  
Sandy M. Yishan ◽  
Samuel S. Harris ◽  
Aline Blistein ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strongly Correlated ◽  
App Processing ◽  
Term Potentiation ◽  
Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

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.

Mitral and Tufted Cells Differ in the Decoding Manner of Odor Maps in the Rat Olfactory Bulb

2004 ◽  
Vol 91 (6) ◽  
pp. 2532-2540 ◽  
Author(s):  
Shin Nagayama ◽  
Yuji K. Takahashi ◽  
Yoshihiro Yoshihara ◽  
Kensaku Mori
Keyword(s):  
Olfactory Bulb ◽  
Spike Activity ◽  
Homologous Series ◽  
Morphological Difference ◽  
Aliphatic Acid ◽  
Mitral Cells ◽  
Firing Rates ◽  
Aliphatic Acids ◽  
Projection Pattern ◽  
Tufted Cells

Mitral and tufted cells in the mammalian olfactory bulb are principal neurons, each type having distinct projection pattern of their dendrites and axons. The morphological difference suggests that mitral and tufted cells are functionally distinct and may process different aspects of olfactory information. To examine this possibility, we recorded odorant-evoked spike responses from mitral and middle tufted cells in the aliphatic acid- and aldehyde-responsive cluster at the dorsomedial part of the rat olfactory bulb. Homologous series of aliphatic acids and aldehydes were used for odorant stimulation. In response to adequate odorants, mitral cells showed spike responses with relatively low firing rates, whereas middle tufted cells responded with higher firing rates. Examination of the molecular receptive range (MRR) indicated that most mitral cells exhibited a robust inhibitory MRR, whereas a majority of middle tufted cells showed no or only a weak inhibitory MRR. In addition, structurally different odorants that activated neighboring clusters inhibited the spike activity of mitral cells, whereas they caused no or only a weak inhibition in the middle tufted cells. Furthermore, responses of mitral cells to an adequate excitatory odorant were greatly inhibited by mixing the odorant with other odorants that activated neighboring glomeruli. In contrast, odorants that activated neighboring glomeruli did not significantly inhibit the responses of middle tufted cells to the adequate excitatory odorant. These results indicate a clear difference between mitral and middle tufted cells in the manner of decoding the glomerular odor maps.

scholarly journals Massive normalization of olfactory bulb output in mice with a 'monoclonal nose'

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Benjamin Roland ◽  
Rebecca Jordan ◽  
Dara L Sosulski ◽  
Assunta Diodato ◽  
Izumi Fukunaga ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Transgenic Mice ◽  
Neural Correlates ◽  
Mitral Cell ◽  
Inhibitory Circuits ◽  
Cell Responses ◽  
Mechanistic Basis ◽  
Signal Normalization ◽  
Whole Cell Recordings

Perturbations in neural circuits can provide mechanistic understanding of the neural correlates of behavior. In M71 transgenic mice with a “monoclonal nose”, glomerular input patterns in the olfactory bulb are massively perturbed and olfactory behaviors are altered. To gain insights into how olfactory circuits can process such degraded inputs we characterized odor-evoked responses of olfactory bulb mitral cells and interneurons. Surprisingly, calcium imaging experiments reveal that mitral cell responses in M71 transgenic mice are largely normal, highlighting a remarkable capacity of olfactory circuits to normalize sensory input. In vivo whole cell recordings suggest that feedforward inhibition from olfactory bulb periglomerular cells can mediate this signal normalization. Together, our results identify inhibitory circuits in the olfactory bulb as a mechanistic basis for many of the behavioral phenotypes of mice with a “monoclonal nose” and highlight how substantially degraded odor input can be transformed to yield meaningful olfactory bulb output.

scholarly journals Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons

2019 ◽  
Author(s):  
Paloma P Maldonado ◽  
Alvaro Nuno-Perez ◽  
Jan Kirchner ◽  
Elizabeth Hammock ◽  
Julijana Gjorgjieva ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Spontaneous Activity ◽  
Sensory Processing ◽  
Activity Patterns ◽  
Network Activity ◽  
Synaptic Connections ◽  
Pairwise Correlations ◽  
Early Brain Development

SummarySpontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+ (SST) interneurons specifically. Accordingly, silencing SST+ neurons pharmacogenetically fully blocked oxytocin’s effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.

Direct Excitation of Mitral Cells Via Activation of α1-Noradrenergic Receptors in Rat Olfactory Bulb Slices

2001 ◽  
Vol 86 (5) ◽  
pp. 2173-2182 ◽  
Author(s):  
Abdallah Hayar ◽  
Phillip M. Heyward ◽  
Thomas Heinbockel ◽  
Michael T. Shipley ◽  
Matthew Ennis
Keyword(s):  
Olfactory Bulb ◽  
Locus Coeruleus ◽  
Equilibrium Potential ◽  
Channel Blockers ◽  
Mitral Cells ◽  
Patch Clamp Recording ◽  
Whole Cell ◽  
Inward Current

The main olfactory bulb receives a significant modulatory noradrenergic input from the locus coeruleus. Previous in vivo and in vitro studies showed that norepinephrine (NE) inputs increase the sensitivity of mitral cells to weak olfactory inputs. The cellular basis for this action of NE is not understood. The goal of this study was to investigate the effect of NE and noradrenergic agonists on the excitability of mitral cells, the main output cells of the olfactory bulb, using whole cell patch-clamp recording in vitro. The noradrenergic agonists, phenylephrine (PE, 10 μM), isoproterenol (Isop, 10 μM), and clonidine (3 μM), were used to test for the functional presence of α1-, β-, and α2-receptors, respectively, on mitral cells. None of these agonists affected olfactory nerve (ON)–evoked field potentials recorded in the glomerular layer, or ON-evoked postsynaptic currents recorded in mitral cells. In whole cell voltage-clamp recordings, NE (30 μM) induced an inward current (54 ± 7 pA, n= 16) with an EC50 of 4.7 μM. Both PE and Isop also produced inward currents (22 ± 4 pA, n = 19, and 29 ± 9 pA, n = 8, respectively), while clonidine produced no effect ( n = 6). In the presence of TTX (1 μM), and blockers of excitatory and inhibitory fast synaptic transmission [gabazine 5 μM, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) 10 μM, and (±)-2-amino-5-phosphonopentanoic acid (APV) 50 μM], the inward current induced by PE persisted (EC50 = 9 μM), whereas that of Isop was absent. The effect of PE was also observed in the presence of the Ca2+ channel blockers, cadmium (100 μM) and nickel (100 μM). The inward current caused by PE was blocked when the interior of the cell was perfused with the nonhydrolyzable GDP analogue, GDPβS, indicating that the α1 effect is mediated by G-protein coupling. The current-voltage relationship in the absence and presence of PE indicated that the current induced by PE decreased near the equilibrium potential for potassium ions. In current-clamp recordings from bistable mitral cells, PE shifted the membrane potential from the downstate (−52 mV) toward the upstate (−40 mV), and significantly increased spike generation in response to perithreshold ON input. These findings indicate that NE excites mitral cells directly via α1 receptors, an effect that may underlie, at least in part, increased mitral cell responses to weak ON input during locus coeruleus activation in vivo.

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