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The structural plasticity of the axon initial segment (AIS) contributes to the homeostatic control of activity and optimizes the function of neural circuits; however, the underlying mechanisms are not fully understood. In this study, we prepared a slice culture containing nucleus magnocellularis from chickens of both sexes that reproduces most features of AIS plasticityin vivo, regarding its effects on characteristics of AIS and cell-type specificity, and revealed that microtubule reorganization via activation of CDK5 underlies plasticity. Treating the culture with a high-K+medium shortened the AIS and reduced sodium current and membrane excitability, specifically in neurons tuned to high-frequency sound, creating a tonotopic difference in AIS length in the nucleus. Pharmacological analyses revealed that this AIS shortening was driven by multiple Ca2+pathways and subsequent signaling molecules that converge on CDK5 via the activation of ERK1/2. AIS shortening was suppressed by overexpression of dominant-negative CDK5, whereas it was facilitated by the overexpression of p35, an activator of CDK5. Notably, p35(T138A), a phosphorylation-inactive mutant of p35, did not shorten the AIS. Moreover, microtubule stabilizers occluded AIS shortening during the p35 overexpression, indicating that CDK5/p35 mediated AIS shortening by promoting disassembly of microtubules at distal AIS. This study highlights the importance of microtubule reorganization and regulation of CDK5 activity in structural AIS plasticity and the tuning of AIS characteristics in neurons.SIGNIFICANCE STATEMENTThe structural plasticity of AIS has a strong impact on the output of neurons and plays a fundamental role in the physiology and pathology of the brain. However, the mechanisms linking neuronal activity to structural changes in AIS are not well understood. In this study, we prepared an organotypic culture of avian auditory brainstem, reproducing most AIS plasticity featuresin vivo, and we revealed that activity-dependent AIS shortening occurs through the disassembly of microtubules at distal AIS via activation of CDK5/p35 signals. This study emphasizes the importance of microtubule reorganization and regulation of CDK5 activity in structural AIS plasticity and tonotopic differentiation of AIS structures in the brainstem auditory circuit.

Background: Video analysis of body and gaze movements has recently become widespread, mainly in the field of engineering, however, few medical studies have used motion capture and eye-tracking systems. The aim of this study was to test the hypothesis that head movements and gaze distribution during tracheal intubation differ between practitioners who are expert at tracheal intubation and those who are novice at tracheal intubation as a secondary analysis of our previous study. Methods: Practitioners who were either novices or experts at tracheal intubation using Macintosh laryngoscopes were recruited. Head movement and gaze distribution during tracheal intubation into a mannequin were recorded using motion capture and eye-tracking systems and analyzed according to 3 phases: phase A (mouth opening), B (obtaining vocal cord view), and C (tracheal intubation). The values obtained were compared between novices and experts. Results: Intra-group comparison showed significant differences in the height of the head and forward-backward head tilt during tracheal intubation in the experts and novices, respectively. Inter-group comparison showed significant differences at each phase except for the height of the head at phase A

Background: Video laryngoscopy (VL) is an attractive airway management device; however, its userʼs motion during tracheal intubation (TI) has not been evaluated. Therefore, this study aimed to investigate the differences in head and eye movement during TI using VL, McGRATH ® , between experts and novices. Methods: Time for TI, head movements, and gaze distribution during TI in a mannequin with McGRATH ® were recorded using motion capture and eye-tracking systems. TI was divided into three phases: A) from mouth opening to laryngoscope insertion, B) from the insertion into the mouth to enable visualization of the vocal cords, and C) from holding a constant vocal cord view to the finish of intubation. Data were compared between the experts and novices according to the phases. Results: In the experts, total TI time was significantly shorter (17.5 vs. 20.5 sec, p<0.001), and the duration of Phases A and C were significantly shorter (A: 5.0 vs. 6.4 sec, p<0.001; C: 8.1 vs. 9.2 sec, p=0.031). The intra-group comparison showed the head height in both groups significantly decreased until the Phase B and significantly increased in Phase C. Inter-group comparison showed the head heights in the Phases B and C were significantly lower in the novices (B: 152.2 vs. 142.6 cm, p<0.001; C: 157.4 vs. 145.9 cm, p<0.001). The height differences between the occipital and temporal regions indicated both groups turned their faces down from Phase A to B and upward in Phase C. The extent of head tilting in each phase was significantly larger in the novices. Gaze analysis indicated that while the experts continued looking down and further throughout TI, the novices looked up during Phases B and C. Conclusion: Posture and gaze distribution during TI using McGRATH® were different between the novices and experts. These results should be considered in instructing and learning TI.

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