TY - JOUR T1 - Cortical Presynaptic Boutons Progressively Engulf Spinules As They Mature JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0426-19.2020 SP - ENEURO.0426-19.2020 AU - Charles Campbell AU - Sarah Lindhartsen AU - Adam Knyaz AU - Alev Erisir AU - Marc Nahmani Y1 - 2020/09/18 UR - http://www.eneuro.org/content/early/2020/09/18/ENEURO.0426-19.2020.abstract N2 - Despite decades of discussion in the neuroanatomical literature, the role of the synaptic ‘spinule’ in synaptic development and function remains elusive. Canonically, spinules are finger-like projections that emerge from postsynaptic spines and can become enveloped by presynaptic boutons. When a presynaptic bouton encapsulates a spinule in this manner, the membrane apposition between the spinule and surrounding bouton can be significantly larger than the membrane interface at the synaptic active zone. Hence, spinules may represent a mechanism for extrasynaptic neuronal communication, and/or may function as structural ‘anchors’ that increase the stability of cortical synapses. Yet despite their potential to impact synaptic function, we have little information on the percentages of developing and adult cortical bouton populations that contain spinules, the percentages of these cortical spinule-bearing boutons (SBBs) that contain spinules from distinct neuronal/glial origins, or whether the onset of activity or cortical plasticity are correlated with increased prevalence of cortical SBBs. Here, we employed 2D and 3D electron microscopy to determine the prevalence of spinules in excitatory presynaptic boutons at key developmental time points in the primary visual cortex (V1) of female and male ferrets. We find that the prevalence of SBBs in V1 increases across postnatal development, such that ∼25% of excitatory boutons in late adolescent ferret V1 contain spinules. In addition, we find that a majority of spinules within SBBs at later developmental time points emerge from postsynaptic spines and adjacent boutons/axons, suggesting that synaptic spinules may enhance synaptic stability and allow for axo-axonal communication in mature sensory cortex.Significance Statement Synaptic spinules are finger-like projections from neurites that can become completely embedded within presynaptic boutons, potentially enhancing synaptic communication and stability. Yet while their existence has been discussed for decades, spinule prevalence, projection origins, and relationship to neocortical sensory activity remain unknown. In this study, we employed 2D and 3D electron microscopy techniques to characterize the development of excitatory cortical spinule-bearing boutons (SBBs) and their relationship to sensory activity and plasticity. Our results demonstrate that neocortical presynaptic SBB prevalence is not correlated with the onset of sensory activity or heightened cortical plasticity, and that by late adolescence nearly one-quarter of presynaptic boutons contain a spinule. Hence, synaptic spinules may play progressively important roles in cortical function as these synapses mature. ER -