Dataset Information

Developmental regulation of metabotropic glutamate receptor 1 splice variants in olfactory bulb mitral cells.

ABSTRACT: Alternative splicing of the metabotropic glutamate receptor 1 (mGluR1) receptor gene generates two major receptor isoforms, mGluR1a and mGluR1b, differing in intracellular function and distribution. However, little is known on the expression profiles of these variants during development. We examined the mRNA expression profile of mGluR1a/b in microdissected layers and acutely isolated mitral cells in the developing mouse olfactory bulb. This analysis showed that the two mGluR1 variants are differentially regulated within each bulb layer. During the first postnatal week, the mGluR1a isoform replaces GluR1b in the microdissected mitral cell layer (MCL) and in isolated identified mitral cells, coinciding with a developmental epoch of mitral cell dendritic reorganization. Although mGluR1a mRNA is expressed at high levels in both the adult external plexiform layer (EPL) and MCL, Western blotting analysis reveals a marked reduction of the mGluR1a protein in the MCL, where mitral cell bodies are located, and strong labeling in the EPL, which contains mitral cell dendrites. This suggests that there is increased dendritic trafficking efficiency of the receptor in adult. The temporal and spatial shift in mGluR1b/a expression suggests distinct roles of the mGluR1 isoforms, with mGluR1b potentially involved in the early mitral cell maturation and mGluR1a in dendritic and synapse function.

SUBMITTER: Bovolin P

PROVIDER: S-EPMC2743089 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Developmental regulation of metabotropic glutamate receptor 1 splice variants in olfactory bulb mitral cells.

Bovolin P P Bovetti S S Fasolo A A Katarova Z Z Szabo G G Shipley M T MT Margolis F L FL Puche A C AC

Journal of neuroscience research 20090201 2

Alternative splicing of the metabotropic glutamate receptor 1 (mGluR1) receptor gene generates two major receptor isoforms, mGluR1a and mGluR1b, differing in intracellular function and distribution. However, little is known on the expression profiles of these variants during development. We examined the mRNA expression profile of mGluR1a/b in microdissected layers and acutely isolated mitral cells in the developing mouse olfactory bulb. This analysis showed that the two mGluR1 variants are diffe ...[more]

PMID: 18816797

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Project description:The endocannabinoid (eCB) signaling system has been functionally implicated in many brain regions. Our understanding of the role of cannabinoid receptor type 1 (CB1) in olfactory processing remains limited. Cannabinoid signaling is involved in regulating glomerular activity in the main olfactory bulb (MOB). However, the cannabinoid-related circuitry of inputs to mitral cells in the MOB has not been fully determined. Using anatomical and functional approaches we have explored this question. CB1 was present in periglomerular processes of a GAD65-positive subpopulation of interneurons but not in mitral cells. We detected eCBs in the mouse MOB as well as the expression of CB1 and other genes associated with cannabinoid signaling in the MOB. Patch-clamp electrophysiology demonstrated that CB1 agonists activated mitral cells and evoked an inward current, while CB1 antagonists reduced firing and evoked an outward current. CB1 effects on mitral cells were absent in subglomerular slices in which the olfactory nerve layer and glomerular layer were removed, suggesting the glomerular layer as the site of CB1 action. We previously observed that GABAergic periglomerular cells show the inverse response pattern to CB1 activation compared with mitral cells, suggesting that CB1 indirectly regulates mitral cell activity as a result of cellular activation of glomerular GABAergic processes . This hypothesis was supported by the finding that cannabinoids modulated synaptic transmission to mitral cells. We conclude that CB1 directly regulates GABAergic processes in the glomerular layer to control GABA release and, in turn, regulates mitral cell activity with potential effects on olfactory threshold and behavior.NEW & NOTEWORTHY Cannabinoid signaling with cannabinoid receptor type 1 (CB1) is involved in the regulation of glomerular activity in the main olfactory bulb (MOB). We detected endocannabinoids in the mouse MOB. CB1 was present in periglomerular processes of a GAD65-positive subpopulation of interneurons. CB1 agonists activated mitral cells. CB1 directly regulates GABAergic processes to control GABA release and, in turn, regulates mitral cell activity with potential effects on olfactory threshold and behavior.

Project description:Here we present a detailed statistical analysis of the discharge characteristics of mitral cells of the main olfactory bulb of urethane-anesthetized rats. Neurons were recorded from the mitral cell layer, and antidromically identified by stimuli applied to the lateral olfactory tract. All mitral cells displayed repeated, prolonged bursts of action potentials typically lasting >100 sec and separated by similarly long intervals; about half were completely silent between bursts. No such bursting was observed in nonmitral cells recorded in close proximity to mitral cells. Bursts were asynchronous among even adjacent mitral cells. The intraburst activity of most mitral cells showed strong entrainment to the spontaneous respiratory rhythm; similar entrainment was seen in some, but not all nonmitral cells. All mitral cells displayed a peak of excitability at ~25 msec after spikes, as reflected by a peak in the interspike interval distribution and in the corresponding hazard function. About half also showed a peak at about 6 msec, reflecting the common occurrence of doublet spikes. Nonmitral cells showed no such doublet spikes. Bursts typically increased in intensity over the first 20-30 sec of a burst, during which time doublets were rare or absent. After 20-30 sec (in cells that exhibited doublets), doublets occurred frequently for as long as the burst persisted, in trains of up to 10 doublets. The last doublet was followed by an extended relative refractory period the duration of which was independent of train length. In cells that were excited by application of a particular odor, responsiveness was apparently greater during silent periods between bursts than during bursts. Conversely in cells that were inhibited by a particular odor, responsiveness was only apparent when cells were active. Extensive raw (event timing) data from the cells, together with details of those analyses, are provided as supplementary material, freely available for secondary use by others.

Dataset Information

Developmental regulation of metabotropic glutamate receptor 1 splice variants in olfactory bulb mitral cells.

Publications

Developmental regulation of metabotropic glutamate receptor 1 splice variants in olfactory bulb mitral cells.

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