An Olfactory Memory Circuit

Episodic memory is defined simply as memory for what happened, when, and where. The hippocampus mediates episodic memory and represents contextual information using the parameters of space and time, including where an event unfolded and the sequential order of related events. Episodic recollections are characterized by rich multisensory details, yet the mechanisms underlying the reinstatement of these non-spatiotemporal aspects of experience are unknown. In this thesis, we identified direct, topographically organized hippocampal projections to a poorly understood ring-like structure known as the anterior olfactory nucleus (AON). We demonstrated that manipulation of the hippocampal-AON pathway can influence odour perception and odour-guided behaviours. Selective inhibition of hippocampal-AON projections impaired mice in their ability to recognize odours associated with the spatial and/or temporal aspects of their environment. We also revealed that AON activity is generated by coincident olfactory and contextual inputs arriving from the olfactory bulb and hippocampus, respectively. Thus, we hypothesized that the AON acts as the physical repository for populations of neurons representing previously encountered odours within the context in which they occurred. The precise pattern of activity produced by the AON therefore composes the olfactory memory trace, or “odour engram”. To this end, we used a tamoxifen-inducible Cre recombinase system to control the timing of gene expression in the AON. In combination with chemo- and optogenetic tools, we manipulated tagged AON neuronal populations in a carefully designed set of behavioural paradigms. We found that AON activity is necessary and sufficient for driving the behavioural expression of specific odour memories, thereby establishing the AON as the long-term storage site for contextually-based odour engrams. This thesis represents the first demonstration of the neural substrate of odour memory in vertebrates, satisfying all criteria used for defining an engram. The ease and suitability of using olfaction will undoubtedly position the hippocampal-AON pathway as an ideal circuit model for investigating fundamental mnemonic and cognitive principles. Indeed, this model can become particularly important in translational research that may yet lead to the development of therapeutic targets for disorders of memory, such as Alzheimer’s disease.Ph.D

Topographic Organization of Hippocampal Inputs to the Anterior Olfactory Nucleus

Top-down processes conveying contextual information play a major role in shaping odor representations within the olfactory system, yet the underlying mechanisms are poorly understood. The hippocampus (HPC) is a major source of olfactory top-down modulation, providing direct excitatory inputs to the anterior olfactory nucleus (AON). However, HPC-AON projections remain uncharacterized. In an effort to understand how hippocampal inputs are distributed within the AON, we systematically outlined their organization using anterograde and retrograde tracing methods. We found that AON-projecting hippocampal pyramidal neurons are located mostly in the ventral two-thirds of the HPC and are organized topographically such that cells with a ventral to intermediate hippocampal point of origin terminate, respectively, at the medial to lateral AON. Our neuroanatomical findings suggest a potential role for the HPC in the early processing and contextualization of odors which merits further investigation

Evidence for a left ear bias in incidence of Meniere’s disease

Objective: to explore a side of lesion differences in Meniere’s disease (MD).Design: a retrospective review (2019–2021) was conducted of patients with definite MD, as defined by 2015 Bárány Society diagnostic criteria. Testing information included pure tone audiometry, tympanometry, and extra-tympanic electrocochleography (ECochG). Normative ECochG data from healthy subjects determined the 95% cut-off value for clinical abnormality.Study sample: 107 patients with definite MD were included in the study and 40 healthy controls.Results: the review identified 75 patients with unilateral MD and 32 patients with bilateral MD according to their clinical histories. 79% of unilateral cases were found to have MD on the L ear. 94% of bilateral MD cases had L ears more affected than R ears. Objective ECochG testing indicated a greater incidence of elevated SP/AP area curve and amplitude ratios in L ears. On binomial testing, all results indicate a highly significant bias of MD to the L side.Conclusions: unilateral MD appears more common on the L side than the R, suggesting that the disease process underlying MD is not symmetrical. MD also appears more common in females than males. It appears that there is a physiological asymmetry in the progression/cause of MD.Financial disclosures: this study was funded by Deanship of Scientific Research, the University of Jordan.Disclosure statement: no potential conflict of interest was reported by the authors. <br/