Early and Late Phases of Sensory-Evoked Olfactory Bulb Inhibition Are Mediated by Parallel Local Circuits: Attenuation of Fast Tufted Cell Axo-dendritic Inputs to Granule Cells by Adenosine A1 Receptors

感觉诱发的嗅球抑制的早期和晚期阶段由平行的局部回路介导:腺苷A1受体减弱快速簇状细胞轴突树突对颗粒细胞的输入

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Abstract

Across species, simple olfactory operations primarily utilize long-range excitatory interconnections. More complex tasks, such as fine odor discrimination and plasticity, rely on local inhibitory circuits. In the olfactory bulb, previous studies focused on measuring activity patterns following broad activation of sensory inputs and highlighted the central role canonical dendrodendritic circuits play in sculpting principal cell firing patterns. The primary goal of this study is to define the inhibitory local circuits activated by focal stimulation of a single olfactory bulb glomerulus in olfactory bulb slices prepared from rats of either sex. This approach enables dissection of circuit mechanisms normally obscured by the multiglomerular activation patterns natural odorants elicit. Using glomerular stimulation, we identified two distinct local circuits that contribute to sensory-evoked inhibition and operate at different time periods. We further show these circuits are differentially affected by adenosine A1 receptor (A1R) activation. We utilize multiple experimental approaches to show early-phase mitral cell inhibition arises through excitatory synapses formed by axon collaterals of tufted cells onto the proximal dendrites of GABAergic granule cells. Blockade of NMDARs greatly attenuates dendrodendritic inhibition but fails to block the large initial phase of mitral cell inhibition. In contrast, activation of A1Rs attenuates both early-phase mitral cell inhibition and the underlying axo-dendritic excitation of granule cells. We conclude that two independent bulbar excitatory circuits converge on granule cells to generate temporally distinct phases of sensory-evoked inhibition, with A1R activation revealing a novel tufted cell-mediated pathway that contributes to early-phase responses.

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