Abstracts

Rationale: The main olfactory bulb (MOB) is the first relay at the central nervous system  responsible for odor stimuli processing, which maintains connections with various brain structures involved in temporal lobe epilepsy, such as the hippocampus (HPC). Several reports have indicated that ablation or electrical stimulation of the MOB induce epilepsy. However, it is currently unknown whether chronic stimulation with a wide variety of odorants, also known as olfactory enrichment (OE), influences epileptiform activity in the HPC and the MOB. Despite that OE produces therapeutic effects in a variety of neurological pathologies such as Alzheimer's disease, Parkinson's disease, anxiety and depression, its effects on epileptiform activity have not yet been reported. In this investigation, we proposed to analyze the effects of OE on the epileptiform activity in the MOB and the HPC. Methods: CD-1 male mice underwent an OE protocol (21 different odors, 1 odor per day, 2 h per day), matched with control animals that under identical conditions, but without any odor exposure. At the end of the OE, slices from both the MOB and the HPC were obtained. For in vitro experiments, the local field potential of both structures was recorded under basal conditions and, subsequently, epileptiform activity was induced by bath administration of 4-aminopyridine (4AP; 100μM). For in vivo experiments, animals were implanted with electrodes in the HPC and in the MOB. The hippocampal post-discharge threshold was evaluated as well as the spontaneous activity of both the HPC and the MOB was recorded before and during status epilepticus induced with pilocarpine (300 mg/kg). The experimental procedures were approved by the Bioethics Committee of the Institute of Neurobiology at UNAM and were performed in accordance with the guidelines of the Official Mexican Norm for the Use and Care of Laboratory Animals (Norma Oficial Mexicana NOM-062-ZOO, 1999) and the Institutional Animal Care and Use Committee Guidebook (NIH publication 80-23, Bethesda, MD,USA, 1996). Results: We found that OE induces an increase in the power of HPC and MOB spontaneous network activity, maily in the gamma frequency band (30-120 Hz), while potentiates the epileptiform activity induced with 4AP and pilocarpine, both in vitro (n= 12; p<0.05) and in vivo (n= 11; p<0.05). Likewise, the OE induces a decrease in hippocampal post-discharge threshold. Conclusions: OE increases the excitability and seizures-susceptibility of the HPC and the MOB. Our data indicate a OE induces a reconfiguration of several neural networks that makes animals susceptible for the induction of epileptiform activity. Possibly, OE favors synchronization between limbic structures involved in the processing of olfactory information, such as HPC and MOB that, however, makes them prone to seizures Funding: No funding