Extraglomerular Excitation of Rat Olfactory Bulb Mitral Cells by Depolarizing GABAergic Synaptic Input

• Published in: The Journal of neuroscience 2022-09, Vol.42 (36), p.6878-6893
• Main Authors: Pressler, R Todd, Strowbridge, Ben W
• Format: Article
• Language: English
• Subjects: Action potential; Bicuculline; Depolarization; Excitation; Glutamatergic transmission; Glutamic acid receptors (ionotropic); Granule cells; Interneurons; Mitral cells; Olfactory bulb; Olfactory stimuli; Picrotoxin; Receptors; Synapses; γ-Aminobutyric acid A receptors
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.0094-22.2022

Principal cells in the olfactory bulb (OB), mitral and tufted cells, receive direct sensory input and generate output signals that are transmitted to downstream cortical targets. Excitatory input from glutamatergic receptor neurons are the primary known sources of rapid excitation to OB principal cells. Principal cells also receive inhibitory input from local GABAergic interneurons in both the glomerular and plexiform layers. Previous work suggests that the functional effect of these inhibitory inputs, including numerous dendrodendritic synapses with GABAergic granule cells, is to reduce firing probability. In this study, we use patch-clamp recordings to demonstrate that rat (of both sexes) OB mitral cells also can be excited by GABAergic synapses formed outside the glomerular layer. Depolarizing GABAergic responses to focal extracellular stimulation were revealed when fast ionotropic glutamate receptors were blocked, and occurred with short, monosynaptic latencies. These novel synaptic responses were abolished by gabazine, bicuculline, and picrotoxin, three structurally dissimilar GABA receptor antagonists. The likely location of depolarizing GABAergic input to mitral cells was the proximal axon based on the actions of focally applied gabazine and GABA near this region. Excitatory GABAergic synaptic responses, commonly studied in cortical brain regions, have not been reported previously in OB principal cells. Excitatory GABAergic responses promote action potential firing and provide a mechanism for mitral cells to be excited independently of olfactory sensory input. Odor stimuli generate distinctive activity patterns in olfactory bulb neurons through a combination of excitatory and inhibitory synaptic interactions. Most of the excitatory drive to each principal cell is assumed to arise from a highly restricted subset of sensory neurons. This study describes a novel second source of synaptic excitation to principal cells to arise from GABAergic inputs to the proximal axon, a common site of action potential initiation. This new pathway provides a synaptic mechanism to excite OB principal cells that is independent of the canonical excitatory sensory input contained in the glomerular layer.