Measurement of neuro-energetics and neurotransmission in the rat olfactory bulb using 1H and 1H–[13C] NMR spectroscopy

Abstract

The olfactory bulb (OB) plays a fundamental role in the sense of smell and has been implicated in several pathologies, including Alzheimer's disease. Despite its importance, high metabolic activity and unique laminar architecture, the OB is not frequently studied using MRS methods, likely due to the small size and challenging location. Here we present a detailed metabolic characterization of OB metabolism, in terms of both static metabolite concentrations using 1H MRS and metabolic fluxes associated with neuro-energetics and neurotransmission by tracing the dynamic 13C flow from intravenously administered [1,6-13C2]-glucose, [2-13C]-glucose and [2-13C]-acetate to downstream metabolites, including [4-13C]-glutamate, [4-13C]-glutamine and [2-13C]-GABA. The unique laminar architecture and associated metabolism of the OB, distinctly different from that of the cerebral cortex, is characterized by elevated GABA and glutamine levels, as well as increased GABAergic and astroglial energy metabolism and neurotransmission. The results show that, despite the technical challenges, high-quality 1H and 1H–[13C] MR spectra can be obtained from the rat OB in vivo. The derived metabolite concentrations and metabolic rates demonstrate a unique metabolic profile for the OB. The metabolic model provides a solid basis for future OB studies on functional activation or pathological conditions.