Dataset Information

Cell-autonomous role of GFR?1 in the development of olfactory bulb GABAergic interneurons.

ABSTRACT: GFR?1, a receptor for glial cell line-derived neurotrophic factor (GDNF), is critical for the development of the main olfactory system. The olfactory bulb (OB) of Gfra1 knockout mice shows significant reductions in the number of olfactory sensory neurons, mitral and tufted cells, as well as all major classes of OB GABAergic interneurons. However, the latter do not express significant levels of GFR?1, leaving the mechanism of action of GFR?1 in OB interneuron development unexplained. Here we report that GFR?1 is highly expressed in the precursor cells that give rise to all major classes of OB interneurons, but is downregulated as these neurons mature. Conditional ablation of GFR?1 in embryonic GABAergic cells recapitulated the cell losses observed in global Gfra1 knockouts at birth. GFR?1 was also required for the sustained generation and allocation of OB interneurons in adulthood. Conditional loss of GFR?1 altered the migratory behaviour of neuroblasts along the rostral migratory stream (RMS) as well as RMS glial tunnel formation. Together, these data indicate that GFR?1 functions cell-autonomously in subpopulations of OB interneuron precursors to regulate their generation and allocation in the mammalian OB.

SUBMITTER: Zechel S

PROVIDER: S-EPMC5992528 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Cell-autonomous role of GFRα1 in the development of olfactory bulb GABAergic interneurons.

Zechel Sabrina S Fernandez-Suarez Diana D Ibáñez Carlos F CF

Biology open 20180518 5

GFRα1, a receptor for glial cell line-derived neurotrophic factor (GDNF), is critical for the development of the main olfactory system. The olfactory bulb (OB) of Gfra1 knockout mice shows significant reductions in the number of olfactory sensory neurons, mitral and tufted cells, as well as all major classes of OB GABAergic interneurons. However, the latter do not express significant levels of GFRα1, leaving the mechanism of action of GFRα1 in OB interneuron development unexplained. Here we repo ...[more]

PMID: 29716946

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Project description:Within the olfactory bulb (OB), periglomerular (PG) cells consist of various types of interneurons, generally classified by their chemical properties such as neurotransmitter and calcium binding proteins. Calretinin (CR) characterizes morphologically and functionally the more numerous and one of the less known subpopulation of PG cells in the OB. Using of transgenic mice expressing eGFP under the CR promoter, we have tried to obtain the first functional characterization of these cells. Electrophysiological recordings were made in these cells using the patch-clamp technique in thin slices. Using ion substitution methods and specific blockers, we dissected the main voltage-dependent conductances present, obtaining a complete kinetic description for each of them. The more peculiar property of these cells from the electrophysiological point of view is the presence only of a single K-current, A-type - there is no trace of delayed rectifier or of Ca-dependent K-current. Other currents identified, isolated and fully characterized are a fast sodium current, a small L-type calcium current, and an inward rectifier, h-type cationic current. As a consequence of the peculiar complement of voltage-dependent conductances present in these cells, and in particular the absence of delayed-rectifier potassium currents, under the functional point of view these cells present two interesting properties. First, in response to prolonged depolarisations, after the inactivation of the A-current these cells behave as a purely ohmic elements, showing no outward rectification. Second, the CR cells studied can respond only with a single action potential to excitatory inputs; since they send inhibitory synapses to projection neurones, they seem to be designed to inhibit responses of the main neurones to isolated, random excitatory signals, rapidly losing their vetoing effect in response to more structured, repetitive excitatory signals. We propose that a possible role for these rather untalkative interneurons in the intense exchange of messages within the OB might be that of improving the signal-to-noise ratio in the first stages of the olfactory information processing.

Dataset Information

Cell-autonomous role of GFR?1 in the development of olfactory bulb GABAergic interneurons.

Publications

Cell-autonomous role of GFRα1 in the development of olfactory bulb GABAergic interneurons.

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