RESUMEN
BACKGROUND: Parkinson's disease (PD) neuropathology is characterized by intraneuronal protein aggregates composed of misfolded α-Synuclein (α-Syn), as well as degeneration of substantia nigra dopamine neurons. Deficits in olfactory perception and aggregation of α-Syn in the olfactory bulb (OB) are observed during early stages of PD, and have been associated with the PD prodrome, before onset of the classic motor deficits. α-Syn fibrils injected into the OB of mice cause progressive propagation of α-Syn pathology throughout the olfactory system and are coupled to olfactory perceptual deficits. OBJECTIVE: We hypothesized that accumulation of pathogenic α-Syn in the OB impairs neural activity in the olfactory system. METHODS: To address this, we monitored spontaneous and odor-evoked local field potential dynamics in awake wild type mice simultaneously in the OB and piriform cortex (PCX) one, two, and three months following injection of pathogenic preformed α-Syn fibrils in the OB. RESULTS: We detected α-Syn pathology in both the OB and PCX. We also observed that α-Syn fibril injections influenced odor-evoked activity in the OB. In particular, α-Syn fibril-injected mice displayed aberrantly high odor-evoked power in the beta spectral range. A similar change in activity was not detected in the PCX, despite high levels of α-Syn pathology. CONCLUSION: Together, this work provides evidence that synucleinopathy impacts in vivo neural activity in the olfactory system at the network-level.
Asunto(s)
Bulbo Olfatorio/fisiopatología , Corteza Piriforme/fisiopatología , Sinucleinopatías/fisiopatología , alfa-Sinucleína/farmacología , Animales , Ritmo beta/fisiología , Modelos Animales de Enfermedad , Potenciales Evocados/fisiología , Ratones , Bulbo Olfatorio/efectos de los fármacos , Bulbo Olfatorio/metabolismo , Bulbo Olfatorio/patología , Percepción Olfatoria/fisiología , Corteza Piriforme/efectos de los fármacos , Corteza Piriforme/metabolismo , Corteza Piriforme/patología , Sinucleinopatías/inducido químicamente , Sinucleinopatías/metabolismo , Sinucleinopatías/patología , alfa-Sinucleína/administración & dosificaciónRESUMEN
Olfactory impairments, including deficits in odor detection, discrimination, recognition, and changes in odor hedonics, are reported in the early stages of Alzheimer's disease (AD). Rodent models of AD display deficits in odor learning, detection, and discrimination-recapitulating the clinical condition. However, the impact of familial AD genetic mutations on odor hedonics is unknown. We tested 2-, 4-, and 6-month-old 5XFAD (Tg6799) mice in the 5-port odor multiple-choice task designed to assay a variety of odor-guided behaviors, including odor preferences/hedonics. We found that 5XFAD mice investigated odors longer than controls, an effect that was driven by 6-month-old mice. Interestingly, this effect was carried by females in the 5XFAD group, who investigated odors longer than age-matched males. Upon examining behavior directed toward individual odors to test for aberrant odor preferences, we uncovered that 5XFAD females at several ages displayed heightened preferences toward some of the odors, indicating aberrant hedonics. We observed no impairments in the ability to engage in the task in 5XFAD mice. Taken together, 5XFAD mice, particularly 5XFAD females, displayed prolonged odor investigation behavior and enhanced preferences to certain odors. The data provide insight into hedonic alterations that may occur in AD mouse models and how these are influenced by biological sex. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Asunto(s)
Enfermedad de Alzheimer , Modelos Animales de Enfermedad , Odorantes , Filosofía , Caracteres Sexuales , Enfermedad de Alzheimer/genética , Animales , Femenino , Masculino , Ratones , Ratones TransgénicosRESUMEN
Odors are well known to elicit strong emotional and behavioral responses that become strengthened throughout learning, yet the specific cellular systems involved in odor learning and the direct influence of these on behavior are unclear. Here, we investigate the representation of odor-reward associations within two areas recipient of dense olfactory input, the posterior piriform cortex (pPCX) and the olfactory tubercle (OT), using electrophysiological recordings from mice engaged in reward-based learning. Neurons in both regions represent conditioned odors and do so with similar information content, yet the proportion of neurons recruited by conditioned rewarded odors and the magnitudes and durations of their responses are greater in the OT. Using fiber photometry, we find that OT D1-type dopamine-receptor-expressing neurons flexibly represent odors based on reward associations, and using optogenetics, we show that these neurons influence behavioral engagement. These findings contribute to a model whereby OT D1 neurons support odor-guided motivated behaviors.