Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons

Background : Chronic olfactory inflammation (COI) in conditions such as chronic rhinosinusitis significantly impairs the functional and anatomical components of the olfactory system. COI induced by intranasal administration of lipopolysaccharide (LPS) results in atrophy, gliosis, and pro-inflammatory cytokine production in the OB. Although chronic rhinosinusitis patients have smaller olfactory bulbs (OBs), the consequences of olfactory inflammation on OB neurons are largely unknown. Methods : In this study, we investigated the neurological consequence of COI on OB projection neurons, mitral cells (MCs) and tufted cells (TCs). To induce COI, we performed unilateral intranasal administration of LPS to mice for 4 and 10 weeks. Effects of COI on the OB were examined using RNA-sequencing approaches and immunohistochemical analyses. Results : We found that repeated LPS administration upregulated immune-related biological pathways in the OB after 4 weeks. We also determined that the length of TC lateral dendrites in the OB significantly decreased after 10 weeks of COI. The axon initial segment of TCs decreased in number and in length after 10 weeks of COI. The lateral dendrites and axon initial segments of MCs, however, were largely unaffected. In addition, dendritic arborization and axon initial segment reconstruction both took place following a 10-week recovery period. Conclusion : Our findings suggests that olfactory inflammation specifically affects TCs and their integrated circuitry, whereas MCs are potentially protected from this condition. This data demonstrates unique characteristics of the OBs ability to undergo neuroplastic changes in response to stress.

Axon initial segment geometry in relation to motoneuron excitability

The axon initial segment (AIS) responsible for action potential initiation is a dynamic structure that varies and changes together with neuronal excitability. Like other neuron types, alpha motoneurons in the mammalian spinal cord express heterogeneity and plasticity in AIS geometry, including length (AISl) and distance from soma (AISd). The present study aimed to establish the relationship of AIS geometry with a measure of intrinsic excitability, rheobase current, that varies by 20-fold or more among normal motoneurons. We began by determining whether AIS length or distance differed for motoneurons in motor pools that exhibit different activity profiles. Motoneurons sampled from the medial gastrocnemius (MG) motor pool exhibited values for average AISd that were significantly greater than that for motoneurons from the soleus (SOL) motor pool, which is more readily recruited in low-level activities. Next, we tested whether AISd covaried with intrinsic excitability of individual motoneurons. In anesthetized rats, we measured rheobase current intracellularly from MG motoneurons in vivo before labeling them for immunohistochemical study of AIS structure. For 16 motoneurons sampled from the MG motor pool, this combinatory approach revealed that AISd, but not AISl, was significantly related to rheobase, as AIS tended to be located further from the soma on motoneurons that were less excitable. Although a causal relation with excitability seems unlikely, AISd falls among a constellation of properties related to the recruitability of motor units and their parent motoneurons.

BILATERAL COMPLETE FORAMEN OF CIVININI ON ARTIFICIALLY DEFORMED SKULL

The study aimed to investigate the foramen of Civinini using craniological material. 75 skulls were examined, foramen of Civinini was found on one artificially deformed female skull (1.3%) from a catacomb burial, dated I-VII centuries AD. The study used cranioscopic and craniometric methods. Artificial deformation of the skull was classified according to Georg K. Neumann (1942) and was identified as parallelo-fronto-occipital, subtype-saddle-like depression. The skull was metopic; the metopic suture length was 111.11 mm. The initial segment of the metopic suture, 5.26 mm long, was weakly serrated. The Foramen of Civinini was complete and bilateral. The length of the left foramen of Civinini was 3.77 mm, the width was 3.48 mm. The foramen spinosum was absent on the left side; in the basal norm, the pterygospinous bar divided the foramen ovale into two parts, as it were. The length of the right foramen of Civinini was 4.14 mm, the width was 6.19 mm, in other words, the size of the foramen was larger than that of the left one. As on the left side, the pterygospinous bar divided the foramen ovale into two parts in the basal norm.

A sticky situation: regulation and function of protein palmitoylation with a spotlight on the axon and axon initial segment

In neurons, the axon and axon initial segment (AIS) are critical structures for action potential initiation and propagation. Their formation and function rely on tight compartmentalisation, a process where specific proteins are trafficked to and retained at distinct subcellular locations. One mechanism which regulates protein trafficking and association with lipid membranes is the modification of protein cysteine residues with the 16-carbon palmitic acid, known as S-acylation or palmitoylation. Palmitoylation, akin to phosphorylation, is reversible, with palmitate cycling being mediated by substrate-specific enzymes. Palmitoylation is well-known to be highly prevalent among neuronal proteins and is well studied in the context of the synapse. Comparatively, how palmitoylation regulates trafficking and clustering of axonal and AIS proteins remains less understood. This review provides an overview of the current understanding of the biochemical regulation of palmitoylation, its involvement in various neurological diseases, and the most up-to-date perspective on axonal palmitoylation. Through a palmitoylation analysis of the AIS proteome, we also report that an overwhelming proportion of AIS proteins are likely palmitoylated. Overall, our review and analysis confirm a central role for palmitoylation in the formation and function of the axon and AIS and provide a resource for further exploration of palmitoylation-dependent protein targeting to and function at the AIS.