Efficient neuronal processing mechanisms in the olfactory system & insights into impaired brain function in autism spectrum disorder using SHANK3 mice

Le-Jahns, Thi Kim Chi; Rothermel, Markus (Thesis advisor); Spehr, Marc (Thesis advisor); Lampert, Angelika (Thesis advisor)

Aachen : RWTH Aachen University (2022, 2023)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2022


The sense of smell guides our basic human functions - beyond that, it strongly shapes emotion and memory functions and is essential for complex behaviors. The computations mastering brain functions underlying the sense of smell are not yet understood - neither in the healthy brain state, nor when interrupted in neurological conditions. 1) In this doctoral work, we combined two-photon calcium imaging with an AAV-mediated retrograde tracing approach to record from target-defined output streams in the olfactory bulb. We give the first evidence for parallel processing mechanisms in the olfactory system and add new insights into the complexity and multifaceted strategy of neuronal coding efficiency. 2) Using the genetic SHANK3 mouse model for autism, we first of all developed olfactory assays to decipher autism-associated changes in olfactory behavior. Secondly, we established chronic two-photon calcium imaging of GABAergic interneurons in SHANK3 mice during an olfactory discrimination learning task. Our preliminary data could point to a potential contribution of GABAergic interneurons to altered olfactory bulb circuit function, related to the autism risk gene SHANK3 and open up an interesting avenue to decipher the neural cause of Autism Spectrum Disorder.