CCKergic Tufted Cells Differentially Drive Two Anatomically Segregated Inhibitory Circuits in the Mouse Olfactory Bulb

• Published in: The Journal of neuroscience Vol. 40; no. 32; pp. 6189 - 6206
• Main Authors: Sun, Xicui, Liu, Xiang, Starr, Eric R, Liu, Shaolin
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 05.08.2020
• Subjects: Animals; Axon collaterals; Cholecystokinin; Cholecystokinin - genetics; Cholecystokinin - metabolism; Circuits; Dendrites; Electrophysiology; Female; Frequency dependence; GABAergic Neurons - metabolism; GABAergic Neurons - physiology; Genetics; Granule cells; Information processing; Interneurons; Interneurons - metabolism; Interneurons - physiology; Male; Mice; Mice, Inbred C57BL; Mitral cells; Neural Inhibition; Neural networks; Neurons; Olfactory bulb; Olfactory Bulb - cytology; Olfactory Bulb - physiology; Olfactory pathways; Olfactory Pathways - cytology; Olfactory Pathways - physiology; Olfactory receptor neurons; Olfactory stimuli; Optics; Sensory integration; Sensory neurons; Signal processing; Smell; Subpopulations; Synapses; Synaptic depression; Synaptic Potentials; Synaptic transmission; γ-Aminobutyric acid; olfactory bulb; synaptic transmission; synaptic plasticity; projection neurons; neural circuits; inhibitory interneuron
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.0769-20.2020

Delineation of functional synaptic connections is fundamental to understanding sensory processing. Olfactory signals are synaptically processed initially in the olfactory bulb (OB) where neural circuits are formed among inhibitory interneurons and the output neurons mitral cells (MCs) and tufted cells (TCs). TCs function in parallel with but differently from MCs and are further classified into multiple subpopulations based on their anatomic and functional heterogeneities. Here, we combined optogenetics with electrophysiology to characterize the synaptic transmission from a subpopulation of TCs, which exclusively express the neuropeptide cholecystokinin (CCK), to two groups of spatially segregated GABAergic interneurons, granule cells (GCs) and glomerular interneurons in mice of both sexes with four major findings. First, CCKergic TCs receive direct input from the olfactory sensory neurons (OSNs). This monosynaptic transmission exhibits high fidelity in response to repetitive OSN input. Second, CCKergic TCs drive GCs through two functionally distinct types of monosynaptic connections: (1) dendrodendritic synapses onto GC distal dendrites via their lateral dendrites in the superficial external plexiform layer (EPL); (2) axodendritic synapses onto GC proximal dendrites via their axon collaterals or terminals in the internal plexiform layer (IPL) on both sides of each bulb. Third, CCKergic TCs monosynaptically excite two subpopulations of inhibitory glomerular interneurons via dendrodendritic synapses. Finally, sniff-like patterned activation of CCKergic TCs induces robust frequency-dependent depression of the dendrodendritic synapses but facilitation of the axodendritic synapses. These results demonstrated important roles of the CCKergic TCs in olfactory processing by orchestrating OB inhibitory activities. Neuronal morphology and organization in the olfactory bulb (OB) have been extensively studied, however, the functional operation of neuronal interactions is not fully understood. We combined optogenetic and electrophysiological approaches to investigate the functional operation of synaptic connections between a specific population of excitatory output neuron and inhibitory interneurons in the OB. We found that these output neurons formed distinct types of synapses with two populations of spatially segregated interneurons. The functional characteristics of these synapses vary significantly depending on the presynaptic compartments so that these output neurons can dynamically rebalance inhibitory feedback or feedforward to other neurons types in the OB in response to dynamic rhythmic inputs.