Pharmacological manipulation of olfactory bulb granule cell excitability modulates beta oscillations: Testing a model

The mammalian olfactory bulb (OB) generates gamma (40 - 100 Hz) and beta (15 - 30 Hz) oscillations of the local field potential (LFP). Gamma oscillations arise at the peak of inhalation supported by dendrodendritic interactions between glutamatergic mitral cells (MCs) and GABAergic granule cells (GCs). Beta oscillations occur in response to odorants in learning or odor sensitization paradigms, but their generation mechanism and function are still poorly understood. When centrifugal inputs to the OB are blocked, beta oscillations disappear, but gamma oscillations persist. Centrifugal input targets primarily GABAergic interneurons in the GC layer (GCL) and regulates GC excitability, which suggests a causal link between beta oscillations and GC excitability. Previous modeling work from our laboratory predicted that convergence of excitatory/inhibitory inputs onto MCs and centrifugal inputs onto GCs can increase GC excitability sufficiently to drive beta oscillations primarily through voltage dependent calcium channel (VDCC) mediated GABA release, independently of NMDA channels. We test this model by examining the influence of NMDA and muscarinic acetylcholine receptors on GC excitability and beta oscillations. Intrabulbar scopolamine (muscarinic antagonist) infusion decreased or completely suppressed odor-evoked beta in response to a strong stimulus, but increased beta power in response to a weak stimulus, as predicted by our model. Piriform cortex (PC) beta power was unchanged. Oxotremorine (muscarinic agonist) tended to suppress all oscillations, probably from over-inhibition. APV, an NMDA receptor antagonist, suppressed gamma oscillations selectively (in OB and PC), lending support to the models prediction that beta oscillations can be supported by VDCC mediated currents.\n\nNew and NoteworthyO_LIOlfactory bulb beta oscillations rely on granule cell excitability.\nC_LIO_LIReducing granule cell excitability with scopolamine reduces high volatilityinduced beta power but increases low volatility-induced beta power.\nC_LIO_LIPiriform cortex beta oscillations maintain power when olfactory bulb beta power is low, and the system maintains beta band coherence.\nC_LI