Alterations in Piriform and Bulbar Activity/Excitability/Coupling Upon Amyloid-β Administration in vivo Related to Olfactory Dysfunction

Issue title: Translational Research and Drug Discovery for Neurodegeneration: Challenges for Latin America

Guest editors: K.S. Jagannatha Rao, Gabrielle B. Britton, Luisa Lilia Rocha Arrieta, Norberto Garcia-Cairasco, Alberto Lazarowski, Adrián Palacios, Antoni Camins Espuny and Ricardo B. Maccioni

Article type: Research Article

Authors: Martínez-García, Ignacio | Hernández-Soto, Rebeca | Villasana-Salazar, Benjamín | Ordaz, Benito | Peña-Ortega, Fernando^{; *}

Affiliations: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, UNAM-Campus Juriquilla, México

Correspondence: [*] Correspondence to: Fernando Peña-Ortega, PhD. Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Querétaro, QRO, 76230, México. Email: [email protected].

Abstract: Background:Deficits in odor detection and discrimination are premature symptoms of Alzheimer’s disease (AD) that correlate with pathological signs in the olfactory bulb (OB) and piriform cortex (PCx). Similar olfactory dysfunction has been characterized in AD transgenic mice that overproduce amyloid-β peptide (Aβ), which can be prevented by reducing Aβ levels by immunological and pharmacological means, suggesting that olfactory dysfunction depends on Aβ accumulation and Aβ-driven alterations in the OB and/or PCx, as well as on their activation. However, this possibility needs further exploration. Objective:To characterize the effects of Aβ on OB and PCx excitability/coupling and on olfaction. Methods:Aβ oligomerized solution (containing oligomers, monomers, and protofibrils) or its vehicle were intracerebroventricularlly injected two weeks before OB and PCx excitability and synchrony were evaluated through field recordings in vivo and in brain slices. Synaptic transmission from the OB to the PCx was also evaluated in slices. Olfaction was assessed through the habituation/dishabituation test. Results:Aβ did not affect lateral olfactory tract transmission into the PCx but reduced odor habituation and cross-habituation. This olfactory dysfunction was related to a reduction of PCx and OB network activity power in vivo. Moreover, the coherence between PCx-OB activities was also reduced by Aβ. Finally, Aβ treatment exacerbated the 4-aminopyridine-induced excitation in the PCx in slices. Conclusion:Our results show that Aβ-induced olfactory dysfunction involves a complex set of pathological changes at different levels of the olfactory pathway including alterations in PCx excitability and its coupling with the OB. These pathological changes might contribute to hyposmia in AD.

Keywords: Alzheimer’s disease, coherence, hyperexcitability, local field potential, main olfactory bulb, olfactory function, piriform cortex

DOI: 10.3233/JAD-201392

Journal: Journal of Alzheimer's Disease, vol. 82, no. s1, pp. S19-S35, 2021