Modulation of the local field potential oscillation in the olfactory bulb and HDB in the basal forebrain by electrical and odorant stimulation in mice

The glymphatic clearing function has been proposed to be dependent on 40 Hz gamma oscillation, which is fundamental for the pathogenesis of neurodegenerative diseases. It is evident that multisensory and vibrotactile stimulation have been proven to enhance gamma oscillation and boost glymphatic clearance of amyloid load. These multisensory stimulations induce gamma frequency entrainment via thalamus. The cholinergic neurons in basal forebrain provide massive projections to the olfactory bulb, hippocampus, and neocortex. Degeneration of these neurons causes smell loss, memory impairment and recognition deficits during the early stage of Alzheimer’s disease. Cholinergic neuronal degeneration is among the earliest events during AD development. The Olfactory pathway provides a powerful sensation bypassing the thalamus, and the olfactory gamma oscillation is synchronized with hippocampus. The olfactory bulb, hippocampus, and neocortex are modulated by the cholinergic neurons in basal forebrain, which, based our preliminary data, have been shown to be responsive to both odorant and nociceptive stimulus. On the other hand, olfactory LFP oscillations have been proposed as the mechanism that facilitates synchronization of olfactory output and odor information processing. Our team and other labs have reported that neuronal discharge in olfactory bulbs can be increased or depressed by stimulation of horizontal diagonal band (HDB) of the basal forebrain either through electrical or optogenetic stimulation, but how do these stimulations affect the local field potential oscillation remain poorly understood. Here we used electrical stimulation on HDB and investigated the oscillation the olfactory bulb in awake and anesthetized the mice. We observed spontaneous LFP activity in both olfactory bulb and HDB consisting of theta (2 - 12 Hz), beta (15 - 36 Hz) and gamma (40 - 80 Hz) band oscillations. We found that electrical stimulation of HDB (300 mA, 100 Hz, 25 pulses) induced increased spiking activity (Zhan, et al 2014) but did not significantly affect low and high gamma oscillation in the olfactory bulb in both awake and anesthetized mice with urethane (i.e., 1.5 g/kg). We also presented Odorants (sharpie alcohol mixtures: n-propanol, n-butanol and diacetone alcohol) to a different group of mice, which induced increased spiking activity and brief increase of oscillations across all bands of frequencies in the horizontal diagonal band in anesthetized mice. In addition, we used tail pinching that induced increased spiking activity and enhanced oscillation in high (70-100 Hz) and low gamma (40-70 Hz) bands in the horizontal diagonal band in anesthetized mice, but the theta (1-10 Hz) and beta (12-35 Hz) oscillations were not affected significantly. Our experiments suggest that light nociceptive or odor stimulus can increase gamma oscillation in the basal forebrain, thus may contribute to odor representation and may be involved in glymphatic perfusion and neurodegeneration. Karen Toffler Charitable Trust, DC CFAR Pilot Grant and the HUCOM Bridge Fund to XZ This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.