Perioperative Intravenous Dexamethasone Improves Pain and Functional Outcomes After Arthroscopic Rotator Cuff Repair.

Neurons have several dendrites and one special neurite, the axon. Since the times of Ramon y Cajal () typical morphological criteria distinguish the axon from dendrites, all confirmed decades later by neurite-specific molecular signatures. The majority of human neurons in Cajal’s drawings have axons arising from the cell body. Axons start with a smooth, tapering hillock which is followed by the axon initial segment (AIS), the electrogenic domain generating the action potential (Kole and Brette ). The axon continues as non-tapering descending fiber which in pyramidal cells gives rise—often at right angles or recurrent—to thinner collaterals with varicosities. However, axons may as well emerge from a dendrite, a feature now referred to as ‘axon-carrying dendrite’ (AcD) and ‘AcD neurons’. Functionally, mouse hippocampal CA1 AcD pyramidal cells are privileged since the input onto the AcD bypasses the soma, circumvents somatic integration and somatic inhibition, and can initiate action potentials in the axon (Thome et al. ). AcDs are intrinsically more excitable, generating dendritic spikes with higher probability and greater strength. Synaptic input onto AcDs efficiently elicits action potentials with lower thresholds compared to those of non-AcDs due to the short electrotonic distance between input and AIS. These features enable allocortical CA1 AcD pyramidal cells to generate ripple oscillations (Hodapp et al. 2024). Whether or not the same accounts for AcD pyramidal cells of the neocortex and how the AcD configuration affects the working mode of the inhibitory interneurons remains to be shown. AcDs occur in pyramidal neurons of all neocortical layers in rodents, lagomorphs, ungulates, and carnivores, infant and adult macaque and adult and aged human (Peters et al. ; Smit and Uyling ; Van der Loos Peters and Kara ; Ferrer et al. , ; Hübener et al. ; Reblet et al. ; Matsubara et al. ; Prieto and Winer ; Mendizabal-Zubiaga et al. ; Hamada et al. ; Ernst et al. ; Wahle et al. ). In non-primate species, 15–20% of pyramidal cells of layers 2–6 have basal AcD. Axons from apical dendrites are extremely rare. The proportion of basal AcD was lower in macaque and particularly low for supragranular neurons of the human neocortex. Ontogenetically older pyramidal cells of subplate and interstitial cells of the white matter exhibit AcDs to much higher percentages than gray matter pyramidal cells suggestive of evolutionary regulation and cell-type specificity. For instance, subplate axonal loop cells rarely have axons from dendrites (Wahle et al. ). Gray matter interneurons and Cajal-Retzius cells have AcDs at higher percentages than pyramidal cells (Retzius ; Jones ; Meyer ; Meyer and Wahle ; Kisvárday et al. ; Wahle ; Höfflin et al. ; Wahle et al. ; Sobierajski et al. ). The proportion of AcD pyramidal cells in mouse CA1 ranges from about 20% (Benavides-Piccione et al. ) determined with dye injections to about 50% (Thome et al. ) with genetic labeling. Differences in proportions could have been due to sampling strategies since the majority of rodent CA1 AcD pyramidal cells resides in the superficial sublayer of the central part of CA1 in dorsal hippocampus, with much lower proportions in ventral hippocampus and subiculum (Thome et al. ). Alternatively, differences of methods could contribute, such as the validation of the AIS done in the latter study to unequivocally identify the axon in > 700 neurons. In human CA1, AcD pyramidal cells represent 44% (Benavides-Piccione et al. ). A variance by a factor of two has also been found in Thy-1 labeled mouse neocortical pyramidal cells (Wahle et al. ) either due to individual differences of Thy-1 expression or to biological variability. This indicates that only the assessment of large numbers of neurons will yield reliable data. A recent study (Han et al. ) in dissociated hippocampal neurons of Wistar Unilever HsdCpb: WU (Envigo) rats reports AcD neurons as early as 3 days after plating before the onset of synaptogenesis. Interestingly, from days in vitro (DIV) 3 to DIV 5/7 the proportion of hippocampal AcD neurons increases to up to 20% followed by a decrease to about 10% at DIV 21 (Han et al. ). The in vitro proportions are lower than proportions reported in CA1/CA3 in vivo (Thome et al. ; Hodapp et al. ) but comparable to proportions reported in adult non-primate neocortex (Wahle et al. ). Importantly, Han et al. () have meticulously worked out that the axon grows first, that the dendrite which lateron will carry the axon emerges as collateral of the axon close to the soma, and that the joint root harbors tyrosinated microtubuli in an orientation typical for axons. In other words, the ‘axon-is-first’ observation in dissociated cells (Han et al. ) could suggest that an AcD cell actually starts as a ‘dendrite-carrying axon’ (DcA) cell.