Somatostatin Serves a Modulatory Role in the Mouse Olfactory Bulb: Neuroanatomical and Behavioral Evidence

Somatostatin (SOM) and somatostatin receptors (SSTR1–4) are present in all olfactory structures, including the olfactory bulb (OB), where SOM modulates physiological gamma rhythms and olfactory discrimination responses. In this work, histological, viral tracing and transgenic approaches were used to characterize SOM cellular targets in the murine OB. We demonstrate that SOM targets all levels of mitral dendritic processes in the OB with somatostatin receptor 2 (SSTR2) detected in the dendrites of previously uncharacterized mitral-like cells. We show that inhibitory interneurons of the glomerular layer (GL) express SSTR4 while SSTR3 is confined to the granule cell layer (GCL). Furthermore, SOM cells in the OB receive synaptic inputs from olfactory cortical afferents. Behavioral studies demonstrate that genetic deletion of SSTR4, SSTR2 or SOM differentially affects olfactory performance. SOM or SSTR4 deletion have no major effect on olfactory behavioral performances while SSTR2 deletion impacts olfactory detection and discrimination behaviors. Altogether, these results describe novel anatomical and behavioral contributions of SOM, SSTR2 and SSTR4 receptors in olfactory processing

Physiologie de la somatostatine dans le bulbe olfactif de souris (des interneurones somatostatinergiques à la modulation du comportement olfactif)

Le neuropeptide somatostatine est largement exprimé dans le cerveau et son rôle modulateur via ses six récepteurs est bien établi dans les fonctions neuroendocriniennes et cognitives. La présence de la somatostatine et de ses récepteurs dans le système olfactif, et leur déclin dans plusieurs maladies neurodégénératives associées à des troubles précoces du sens de l odorat, suggèrent que ce peptide participe au traitement de l information olfactive. Notre travail démontre que, dans le bulbe olfactif de souris, la somatostatine est exprimée par des interneurones de van Gehuchten précisément situés dans la partie interne de la couche plexiforme externe. Ces interneurones sans axone établissent des synapses dendrodendritiques réciproques avec les dendrites latérales des cellules de projection du bulbe, les cellules mitrales. En agissant sur les récepteurs sst2 exprimés par leurs dendrites, la somatostatine influence la transmission synaptique dendrodendritique entre cellules principales et cellules granulaires qui est l origine d oscillations gamma dans le réseau neuronal bulbaire (40-100 Hz). Les variations de la puissance de ces oscillations induites par le blocage ou l activation du récepteur sst2 sont associées à des modifications du seuil de discrimination olfactive. Ainsi, nos résultats démontrent que la libération endogène de somatostatine participe à la modulation des oscillations gamma bulbaires et à la discrimination olfactive. Ce travail ouvre donc des perspectives sur l implication de la somatostatine dans le traitement de l information sensorielle et dans le fonctionnement des réseaux neuronaux du télencéphale.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Somatostatin interneurons delineate the inner part of the external plexiform layer in the mouse main olfactory bulb

International audienceNeuropeptides play a major role in the modulation of information processing in neural networks. Somatostatin, one of the most concentrated neuropeptides in the brain, is found in many sensory systems including the olfactory pathway. However, its cellular distribution in the mouse main olfactory bulb (MOB) is yet to be characterized. Here we show that approximately 95% of mouse bulbar somatostatin-immunoreactive (SRIF-ir) cells describe a homogeneous population of interneurons. These are restricted to the inner lamina of the external plexiform layer (iEPL) with dendritic field strictly confined to the region. iEPL SRIF-ir neurons share some morphological features of Van Gehuchten short-axon cells, and always express glutamic acid decarboxylase, calretinin, and vasoactive intestinal peptide. One-half of SRIF-ir neurons are parvalbumin-ir, revealing an atypical neurochemical profile when compared to SRIF-ir interneurons of other forebrain regions such as cortex or hippocampus. Somatostatin is also present in fibers and in a few sparse presumptive deep short-axon cells in the granule cell layer (GCL), which were previously reported in other mammalian species. The spatial distribution of somatostatin interneurons in the MOB iEPL clearly outlines the region where lateral dendrites of mitral cells interact with GCL inhibitory interneurons through dendrodendritic reciprocal synapses. Symmetrical and asymmetrical synaptic contacts occur between SRIF-ir dendrites and mitral cell dendrites. Such restricted localization of somatostatin interneurons and connectivity in the bulbar synaptic network strongly suggest that the peptide plays a functional role in the modulation of olfactory processing

Olfactory discrimination learning increases the survival of adult-born neurons in the olfactory bulb.

International audienceIn the olfactory bulb (OB), new neurons are added throughout life, forming an integral part of the functioning circuit. Yet only some of them survive more than a month. To determine whether this turnover depends on olfactory learning, we examined the survival of adult newborn cells labeled with the cell division marker BrdU, administered before learning in an olfactory discrimination task. We report that discrimination learning increases the number of newborn neurons in the adult OB by prolonging their survival. Simple exposure to the pair of olfactory cues did not alter neurogenesis, indicating that the mere activation of sensory inputs during the learning task was insufficient to alter neurogenesis. The increase in cell survival after learning was not uniformly distributed throughout angular sectors of coronal sections of the OB. Monitoring odor activation maps using patterns of Zif268 immediate early gene expression revealed that survival was greater in regions more activated by the non-reinforced odorant. We conclude that sensory activation in a learning context not only controls the total number of newborn neurons in the adult OB, but also refines their precise location. Shaping the distribution of newborn neurons by influencing their survival could optimize the olfactory information processing required for odor discrimination

Pseudomonas fluorescens C7R12 type III secretion system impacts mycorrhization of Medicago truncatula and associated microbial communities

International audienceType three secretion systems (T3SSs) mediate cell-to-cell interactions between Gram-negative bacteria and eukaryotes. We hypothesized that fluorescent pseudomonads harboring T3SS (T3SS+) would be beneficial to arbuscular mycorrhizal symbiosis because non-pathogenic fluorescent pseudomonads have been previously shown to be much more abundant in mycorrhizal than in non-mycorrhizal roots. We tested this hypothesis by comparing mycorrhization and the associated rhizosphere microbial communities of Medicago truncatula grown in a non-sterile soil inoculated with either the T3SS+ mycorrhiza helper bacterium Pseudomonas fluorescens (C7R12) or a T3SS- mutant of the strain. Results showed that the bacterial secretion system was responsible for the promotion of mycorrhization because root colonization by arbuscular mycorrhizal fungi was not promoted by the T3SS- mutant. The observed T3SS-mediated promotion of mycorrhization was associated with changes in the rhizosphere bacterial communities and the increased occurrence of Claroidoglomeraceae within the intraradical arbuscular mycorrhizal fungi. Furthermore, both pseudomonad strains promoted the host-free growth of a model arbuscular mycorrhizal fungus in vitro, suggesting that T3SS-mediated promotion of mycorrhization occurs during plant-fungal interactions rather than during the pre-symbiotic phase of fungal growth. Taken together, these data provide evidence for the involvement of T3SS in promoting arbuscular mycorrhization by a model fluorescent pseudomonad and suggest the implication of interactions between the bacterium and mycorrhizas

Somatostatin Serves a Modulatory Role in the Mouse Olfactory Bulb: Neuroanatomical and Behavioral Evidence

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnbeh.2019.00061/full#supplementary-material PMCID: PMC6465642International audienceSomatostatin (SOM) and somatostatin receptors (SSTR1-4) are present in all olfactory structures, including the olfactory bulb (OB), where SOM modulates physiological gamma rhythms and olfactory discrimination responses. In this work, histological, viral tracing and transgenic approaches were used to characterize SOM cellular targets in the murine OB. We demonstrate that SOM targets all levels of mitral dendritic processes in the OB with somatostatin receptor 2 (SSTR2) detected in the dendrites of previously uncharacterized mitral-like cells. We show that inhibitory interneurons of the glomerular layer (GL) express SSTR4 while SSTR3 is confined to the granule cell layer (GCL). Furthermore, SOM cells in the OB receive synaptic inputs from olfactory cortical afferents. Behavioral studies demonstrate that genetic deletion of SSTR4, SSTR2 or SOM differentially affects olfactory performance. SOM or SSTR4 deletion have no major effect on olfactory behavioral performances while SSTR2 deletion impacts olfactory detection and discrimination behaviors. Altogether, these results describe novel anatomical and behavioral contributions of SOM, SSTR2 and SSTR4 receptors in olfactory processing

Spatial learning and synaptic hippocampal plasticity in type 2 somatostatin receptor knock-out mice

International audienceSomatostatin is implicated in a number of physiological functions in the CNS. These effects are elicited through the activation of at least five receptor subtypes. Among them, sst2 receptors appear the most widely expressed in the cortex and hippocampal region. However, the specific role of this somatostatin receptor subtype in these regions is largely undetermined. In this study, we investigated the role of the sst2 receptor in the hippocampus using mice invalidated for the sst2 gene (sst2 KO mice). Complementary experimental approaches were used. First, mice were tested in behavioral tests to explore the consequences of the gene deletion on learning and memory. Spatial discrimination learning in the radial maze was facilitated in sst2 KO mice, while operant learning of a bar-pressing task was slightly altered. Mice were then processed for electrophysiological study using the ex vivo hippocampal slice preparation. Extracellular recordings in the CA1 area showed an enhancement in glutamatergic (AMPA and NMDA) responses in sst2 KO mice which displayed an increase in the magnitude of the short-term potentiation and long-term depression. In contrast, long-term potentiation was not significantly altered. Taken together, these data demonstrate that somatostatin, acting via sst2 hippocampal receptors, may contribute to a global decrease in glutamate efficiency and consequently alter glutamate-dependent plasticity and spatial learning

Activated Somatostatin Type 2 Receptors Traffic In Vivo in Central Neurons from Dendrites to the Trans Golgi Before Recycling

International audienceUnderstanding the trafficking of G-protein-coupled receptors (GPCRs) is of particular importance, especially when modifications of the neurochemic environment occur as in pathological or therapeutic circumstances. In the central nervous system, although some GPCRs were reported to internalize in vivo, little is known about their trafficking downstream of the endocytic event. To address this issue, distribution and expression pattern of the major somatostatin receptor subtype, the somatostatin type 2 (sst2), was monitored in the hippocampus using immunofluorescence, autoradiographic and immunogold experiments from 10 minutes to 7 days after in vivo injection of the receptor agonist octreotide. We then analyzed whether postendocytic trafficking of the receptor was dependent upon integrity of the microtubule network using colchicine-injected animals. Together, our results suggest that upon agonist stimulation, dendritic receptors are retrogradely transported through a microtubule-dependent mechanism to a trans Golgi domain enriched in the t-SNARE syntaxin 6 and trans Golgi network 38 proteins, before recycling. Because we show that the exit rate from the trans Golgi apparatus back to the plasma membrane (hours) is slower than the entry rate (minutes), the neuronal postendocytic trafficking of sst2 receptor is likely to have functional consequences in several neurological diseases in which an increase in somatostatin release occurs

Drug-Free Nasal Spray as a Barrier against SARS-CoV-2 and Its Delta Variant: In Vitro Study of Safety and Efficacy in Human Nasal Airway Epithelia

The nasal epithelium is a key portal for infection by respiratory viruses such as SARS-CoV-2 and represents an important target for prophylactic and therapeutic interventions. In the present study, we test the safety and efficacy of a newly developed nasal spray (AM-301, marketed as Bentrio) against infection by SARS-CoV-2 and its Delta variant on an in vitro 3D-model of the primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in pre-viral load and post-viral load application on airway epithelium. No toxic effects of AM-301 on the nasal epithelium were found. Prophylactic treatment with AM-301 significantly reduced viral titer vs. controls over 4 days, reaching a maximum reduction of 99% in case of infection from the wild-type SARS-CoV-2 variant and more than 83% in case of the Delta variant. When AM-301 administration was started 24 h after infection, viral titer was reduced by about 12-folds and 3-folds on Day 4. The results suggest that AM-301 is safe and significantly decelerates SARS-CoV-2 replication in cell culture inhibition assays of prophylaxis (pre-viral load application) and mitigation (post-viral load application). Its physical (non-pharmaceutical) mechanism of action, safety and efficacy warrant additional investigations both in vitro and in vivo for safety and efficacy against a broad spectrum of airborne viruses and allergens