Noradrenergic Activity in the Olfactory Bulb Is a Key Element for the Stability of Olfactory Memory

International audienceMemory stability is essential for animal survival when environment and behavioral state change over short or long time spans. The stability of a memory can be expressed by its duration, its perseverance when conditions change as well as its specificity to the learned stimulus. Using optogenetic and pharmacological manipulations in male mice, we show that the presence of noradrenaline in the olfactory bulb during acquisition renders olfactory memories more stable. We show that while inhibition of noradrenaline transmission during an odor-reward acquisition has no acute effects, it alters perseverance, duration, and specificity of the memory. We use a computational approach to propose a proof of concept model showing that a single, simple network effect of noradrenaline on olfactory bulb dynamics can underlie these seemingly different behavioral effects. Our results show that acute changes in network dynamics can have long-term effects that extend beyond the network that was manipulated.SIGNIFICANCE STATEMENT Olfaction guides the behavior of animals. For successful survival, animals have to remember previously learned information and at the same time be able to acquire new memories. We show here that noradrenaline in the olfactory bulb, the first cortical relay of the olfactory information, is important for creating stable and specific olfactory memories. Memory stability, as expressed in perseverance, duration and specificity of the memory, is enhanced when noradrenergic inputs to the olfactory bulb are unaltered. We show that, computationally, our diverse behavioral results can be ascribed to noradrenaline-driven changes in neural dynamics. These results shed light on how very temporary changes in neuromodulation can have a variety of long-lasting effects on neural processing and behavior

Microstructured thin-film electrode technology enables proof of concept of scalable, soft auditory brainstem implants

Auditory brainstem implants (ABIs) provide sound awareness to deaf individuals who are not candidates for the cochlear implant. The ABI electrode array rests on the surface of the cochlear nucleus (CN) in the brainstem and delivers multichannel electrical stimulation. The complex anatomy and physiology of the CN, together with poor spatial selectivity of electrical stimulation and inherent stiffness of contemporary multichannel arrays, leads to only modest auditory outcomes among ABI users. Here, we hypothesized that a soft ABI could enhance biomechanical compatibility with the curved CN surface. We developed implantable ABIs that are compatible with surgical handling, conform to the curvature of the CN after placement, and deliver efficient electrical stimulation. The soft ABI array design relies on precise microstructuring of plastic-metal-plastic multilayers to enable mechanical compliance, patterning, and electrical function. We fabricated soft ABIs to the scale of mouse and human CN and validated them in vitro. Experiments in mice demonstrated that these implants reliably evoked auditory neural activity over 1 month in vivo. Evaluation in human cadaveric models confirmed compatibility after insertion using an endoscopic-assisted craniotomy surgery, ease of array positioning, and robustness and reliability of the soft electrodes. This neurotechnology offers an opportunity to treat deafness in patients who are not candidates for the cochlear implant, and the design and manufacturing principles are broadly applicable to implantable soft bioelectronics throughout the central and peripheral nervous system