Sudden Intrabulbar Amyloid Increase Simultaneously Disrupts Olfactory Bulb Oscillations and Odor Detection

Abstract

There seems to be a correlation between soluble amyloid beta protein (Aβ) accumulation in the main olfactory bulb (OB) and smell deterioration in both Alzheimer’s disease (AD) patients and animal models. Moreover, this loss of smell appears to be related to alterations in neural network activity in several olfactory-related circuits, including the OB, as has been observed in anesthetized animals and brain slices. It is possible that there is a correlation between these two pathological phenomena, but a direct and simultaneous evaluation of the acute and direct effect of Aβ on OB activity while animals are actually smelling has not been performed. Thus, here, we tested the effects of acute intrabulbar injection of Aβ at a low dose (200 pmol) on the OB local field potential before and during the presence of a hidden piece of smelly food. Our results show that Aβ decreases the power of OB network activity while impairing the animal’s ability to reach the hidden food. We found a strong relationship between the power of the OB oscillations and the correlation between OBs and the olfactory detection test scores. These findings provide a direct link between Aβ-induced OB network dysfunction and smell loss in rodents, which could be extrapolated to AD patients.

Protective effects of intracerebroventricular adiponectin against olfactory impairments in an amyloid β1–42 rat model

“…Furthermore, in ex vivo experiments, acute incubation of the OB with oligomeric AβO increases in the spontaneous firing rate of the mitral cells [ 9 ], which in turn send excitatory inputs back to the neurons in the glomerular layer [ 41 ]. Supporting our hypothesis that the acute effects in neuronal excitability of the OB circuits might be involved in the olfactory impairments observed in the present study, Alvarado-Martínez and others [ 36 , 43 ] have demonstrated alterations in the synchronized activity of the OB after AβO exposure, specifically, a decrease in the activation of the granular cell layer, which in turn inhibit the neurons in the mitral cell layer, leading to the hyperexcitability of the MC’s and the glomerular layer, ultimately leading to olfactory impairments after AβO i.c.v. and intra-bulbar administrations.…”

“…In the present study, we did not find significant changes in AβO accumulation in OB or HIPP. This is contrast with what has been reported in genetic models such as the AβPP/PS1 and Tg2576 where AβO accumulation appears at 3 months of age [ 6 , 8 , 10 ], or in chronic models, where AβO is accumulated in high quantities [ 33 – 36 ]. The lack of accumulation is probably due to brain clearance mechanisms, given that the infusions were performed in previously healthy animals [ 37 , 38 ].…”

Increased oscillatory power in a computational model of the olfactory bulb due to synaptic degeneration

“…While the research mentioned above found increases in gamma oscillations, it should also be noted that some studies have found decreases in OB oscillations in the presence of Aβ. Hernández-Soto et al applied Aβ by injection and measured activity in vivo in rat OBs an hour after application [33], and Alvarado-Martínez et al measuring cell activity in mouse and rat OB slices in vitro after bath application of Aβ [78]. Both found overall decreases in OB activity.…”

“…Other frequencies of oscillations are present in the bulb as well, namely theta (2-12 Hz) and beta (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). The precise manner in which PD or AD impacts these oscillations and other OB functions is still a matter of investigation [1,2], although studies have found perturbations in this oscillatory activity in animal OBs in the presence of both PD-like pathology [16,32] and AD-like pathology [18][19][20][21]33].…”

“…Hernández-Soto et al applied Aβ by injection and measured activity in vivo in rat OBs an hour after application[33], and Alvarado-Martínez et al measuring cell activity in mouse and rat OB slices in vitro after bath application of Aβ[78]. Both found overall decreases in OB activity.To our knowledge, few studies have measured olfactory bulb neural activity in the presence of PD-like pathology.…”