The anterior olfactory nucleus revisited - An emerging role for neuropathological conditions?

Olfaction is an important sensory modality for many species and greatly influences animal and human behavior. Still, much about olfactory perception remains unknown. The anterior olfactory nucleus is one of the brain's central early olfactory processing areas. Located directly posterior to the olfactory bulb in the olfactory peduncle with extensive in- and output connections and unique cellular composition, it connects olfactory processing centers of the left and right hemispheres. Almost 20 years have passed since the last comprehensive review on the anterior olfactory nucleus has been published and significant advances regarding its anatomy, function, and pathophysiology have been made in the meantime. Here we briefly summarize previous knowledge on the anterior olfactory nucleus, give detailed insights into the progress that has been made in recent years, and map out its emerging importance in translational research of neurological diseases.

Minimally-invasive insertion strategy and in vivo evaluation of multi-shank flexible intracortical probes.

Chronically implanted neural probes are powerful tools to decode brain activity however, recording population and spiking activity over long periods remains a major challenge. Here, we designed and fabricated flexible intracortical Michigan-style arrays with a shank cross-section per electrode of 250 µm[Formula: see text] utilizing the polymer paryleneC with the goal to improve the immune acceptance. As flexible neural probes are unable to penetrate the brain due to the low buckling force threshold, a tissue-friendly insertion system was developed by reducing the effective shank length. The insertion strategy enabled the implantation of the four, bare, flexible shanks up to 2 mm into the mouse brain without increasing the implantation footprint and therefore, minimizing the acute trauma. In acute recordings from the mouse somatosensory cortex and the olfactory bulb, we demonstrated that the flexible probes were able to simultaneously detect local field potentials as well as single and multi-unit activity. Additionally, the flexible arrays outperformed stiff probes with respect to yield of single unit activity. Following the successful in vivo validation, we further improved the microfabrication towards a double-metal-layer process, and were able to double the number of electrodes per shank by keeping the shank width resulting in a cross-section per electrode of 118 µm[Formula: see text].

Dynamic Impairment of Olfactory Behavior and Signaling Mediated by an Olfactory Corticofugal System.

Processing of olfactory information is modulated by centrifugal projections from cortical areas, yet their behavioral relevance and underlying neural mechanisms remain unclear in most cases. The anterior olfactory nucleus (AON) is part of the olfactory cortex, and its extensive connections to multiple upstream and downstream brain centers place it in a prime position to modulate early sensory information in the olfactory system. Here, we show that optogenetic activation of AON neurons in awake male and female mice was not perceived as an odorant equivalent cue. However, AON activation during odorant presentation reliably suppressed behavioral odor responses. This AON-mediated effect was fast and constant across odors and concentrations. Likewise, activation of glutamatergic AON projections to the olfactory bulb (OB) transiently inhibited the excitability of mitral/tufted cells (MTCs) that relay olfactory input to the cortex. Single-unit MTC recordings revealed that optogenetic activation of glutamatergic AON terminals in the OB transiently decreased sensory-evoked MTC spiking, regardless of the strength or polarity of the sensory response. The reduction in MTC firing during optogenetic stimulation was confirmed in recordings in awake mice. These findings suggest that glutamatergic AON projections to the OB impede early olfactory signaling by inhibiting OB output neurons, thereby dynamically gating sensory throughput to the cortex.SIGNIFICANCE STATEMENT The anterior olfactory nucleus (AON) as an olfactory information processing area sends extensive projections to multiple brain centers, but the behavioral consequences of its activation have been scarcely investigated. Using behavioral tests in combination with optogenetic manipulation, we show that, in contrast to what has been suggested previously, the AON does not seem to form odor percepts but instead suppresses behavioral odor responses across odorants and concentrations. Furthermore, this study shows that AON activation inhibits olfactory bulb output neurons in both anesthetized as well as awake mice, pointing to a potential mechanism by which the olfactory cortex can actively and dynamically gate sensory throughput to higher brain centers.