Table 1.
Investigations of mammalian spinule structure, induction, and possible functions.
| Author, journal, year | Spinule origination and contacts | Cell type, brain region, and species | Mode of induction or developmental state | Microscopy technique and spinule morphology | Proposed spinule functions |
|---|---|---|---|---|---|
| Westrum and Blackstad, J Comp Neurol, 1962 | Postsynaptic projections from the head or stalk of a spine invaginated the presynaptic terminal membrane | Hippocampal stratum radiatum of adult rats | Adulthood | EM; Spinule lengths from 75 to 150 nm and widths from 25 to 100 nm; Narrow, flattened, or leaflike in shape; Continuous with spines, except for very small spines | A feature of Grey type 1 synapses, suggestive of some relationship to impulse transmission |
| Tarrant and Routtenberg, Tissue Cell, 1977 | Postsynaptic membrane projections invaginated presynaptic axonal membranes; Surrounded by presynaptic vesicles in the presynaptic terminal | Hippocampal dentate gyrus and caudate nucleus of adult rats | Adulthood; Spinules occurred within asymmetric synapses; 10.1% of hippocampal synapses contained spinules; 8.5% of caudate nucleus synapses contained spinules | EM; Spherical double membrane structures in cross section; Size varied from simple and shallow to deep and branched with coated vesicles | Material transport between presynaptic with postsynaptic processes and information transmission between neurons |
| Desmond and Levy, Brain Research, 1983 | Postsynaptic structures from concave (cup-shaped) spines invaginated presynaptic terminals of asymmetric synapses | Hippocampal dentate gyrus molecular layer of adult male rats | <13% of the total number of synapses contained spinules in controls; High-frequency stimulation increased number of concave spines | EM; Some concave spine heads bore spinules and were shaped like a W, often with a split PSD | Enhanced synaptic functions |
| Schuster et al., Brain Res, 1990 | Postsynaptic spinules found at axospinous synapses | Hippocampal CA3, CA4, and dentate gyrus of adult rats | Increased density of axospinous synapses containing spinules in the inner molecular layer following LTP via stimulation electrode, implanted stereotactically | EM; Postsynaptic membrane protrusions ran parallel to presynaptic invaginations; Occurred in active zones | Synapse modification via enhanced synaptic efficacy, or trans-endocytosis of postsynaptic membrane or other cargoes for recycling or communication |
| Jones and Calverley, Brain Res, 1991 | Postsynaptic spinules associated with perforated synapses; Large spinules projected into presynaptic terminals | Parietal cortex of rats | Perforated synapses were assessed at 9 ages, from 0.5 months (m) to 22 m, i.e., from youth to old-age; Spinules most prominent in middle age at 12 m | EM; Small spinules noted in young rats (0.5 and 1 m), Short broad spinules in adulthood (7 and 10 m); Large spinules peaked in middle age (12 m) and decreased in old age (18 and 22 m) | A feature of perforated spines that may function in maintenance of PSD surface area |
| Sorra et al., J Comp Neurol, 1998 | Postsynaptic; Originated from edges of nonperforated PSDs or from spine necks; Extended into distal axonal boutons | Developing hippocampus of rats | Development (postnatal day 15) | EM; Projections from spines extended from perforations in PSDs | Synaptic remodeling, formation, and stability; Enhance synaptic transmission |
| Toni et al., J Neurosci, 2001 | Extensions from the postsynaptic membrane into the presynaptic ending | Hippocampal CA1 stratum radiatum of rats | Induction of LTP increased enlarged synapses with segmented and partitioned PSDs, typically containing coated vesicles and large PSD-associated spinules | EM; Small, finger like protrusions were classified as small if shorter than 0.2 μm and large if longer than 0.2 μm | Synaptic remodeling; May underlie the formation of synapses with perforated PSDs |
| Colicos et al., Cell, 2001 | Postsynaptic actin sprouted projections toward new presynaptic actin puncta, resembling axon-dendrite interactions during synaptogenesis | Dissociated hippocampal neurons of rats | Targeted photoconductive stimulation to elicit neuronal excitation; Single tetanus elicited reversable remodeling; Repeated tetanus trains induced stable remodeling and small postsynaptic projections | Live video imaging using standard light microscopy; Small projections | Postsynaptic actin spinules appear to contact the presynaptic actin condensation points and may facilitate presynaptic and postsynaptic actin alignment |
| Dhanrajan et al., Hippocampus, 2004 | Postsynaptic mushroom spine; Emerged from edge of segmented PSD and projected into presynaptic bouton | Hippocampal dentate gyrus of aged (22-month-old) rats | High-frequency stimulation in vivo to induce LTP | Optical microcopy and EM; Increased formation of segmented perforated synapses, which in one example bore a spinule | Increase synaptic strength; Participate in learning and LTP |
| Spacek and Harris, J Neurosci, 2004 | Spinules originated from thin and mushroom spine heads, necks, and axons; Engulfed by presynaptic axons, neighboring axons, or astrocytic processes | Hippocampal stratum radiatum of mature rats | Adulthood | Serial section EM; Short vesicular or long vermiform evaginations | Interact with glia; Mechanism for synaptic competition in the mature brain; Retrograde signaling; Membrane remodeling |
| Stewart et al., Neuroscience, 2005 | Postsynaptic spinule-like protrusions projected from the PSD and connected two thorns | Hippocampal CA3 stratum radiatum of adult rats | Spatial training increased thorny excrescence (TE) volume, perforated PSDs, number of thorns, and formation of spinules | EM; Spinule-like protrusions | Increase TE plasticity and spine complexity |
| Richards et al., Proc Natl Acad Sci, 2005 | Postsynaptic spine head protrusions (SHPs) extended to reach presynaptic boutons | Organotypic hippocampal slice cultures of 6-day-old mice | Glutamate was exogenously applied to TTX treated slices to stimulate neuronal activity, inducing SHPs within 8 min with directionality toward glutamate | Time-lapse confocal microscopy and EM; Glutamate-induced SHPs where longer than those that occurred spontaneously after TTX treatment | Meditate contact with nearby boutons for the formation new synapses in response to glutamate in spines not recently activated by presynaptic glutamate |
| Tao-Cheng et al., Neurosci, 2009 | Postsynaptic spinules invaginated into presynaptic terminals | Organotypic hippocampal slice cultures of 7-day-old rats | Exposure to high K+ for 0.5–5 min to induce depolarization induced numerous spinules at excitatory and inhibitory synapses, which peaked at ~1 min of treatment | EM; Parallel double-membranes; Length from ~80 to ~500 nm; Spinules were pinch-waisted, tubular, or irregular in shape; Pinch-waisted spinules often had a clathrin coating | Absent in synapses at low levels of activity, but formed and disappeared quickly during sustained synaptic activity; Membrane retrieval during synaptic activity |
| Ueda and Hayashi, J Neurosci, 2013 | Postsynaptic spines | Organotypic hippocampal slice cultures of 6–8-day-old rats | Spinules gradually increased dependent on PIP3 during LTP induction by two-photon glutamate uncaging | Two-photon imaging; Filopodia-like; Length of spinules extended quickly, reaching 880 nm after LTP induction, and peaked at 4 min | Retrograde signaling; Formation of new synapses with functional presynaptic boutons for altered synaptic connectivity |
| Chazeau et al., EMBO J, 2014 | Postsynaptic finger-like spine head protrusions (SHPs) | Dissociated hippocampal neuron cultures of rats | Compared F-actin and Arp2/3 movements in mature spines; Cytochalasin D treatment decreased spinule formation | Super-resolution dSTORM/PALM; ~70% of globular or cup shaped spines when imaged at low resolution were composed of several finger-like extensions when imaged by super-resolution | F-actin elongation proteins concentrate at tips of SHPs moving away from PSD; F-actin-driven spine remodeling and motility during structural plasticity |
| Weinhard et al., Nat Commun, 2018 | Postsynaptic sites and dendritic shafts frequently elicited transient spine head filopodia (SHF) from mature spines at microglia contact points | Organotypic hippocampal neuron cultures of 4-day-old C57BL/6J mice | Microglia processes contacted mature, persistent spines, which extended SHFs toward microglia; Some spines relocated to sites of the SHF tips and were more stable than spines without SHFs | Light sheet fluorescence microscopy; Correlative light and electron microscopy (CLEM); Protrusions from spine heads | Microglia-induced spinules mediate synaptic switching and/or stability of mature spines and the formation of new synapses |
| Zaccard et al., Neuron, 2020 | Postsynaptic mushroom spines; Short-lived spinules extended and retracted rapidly, sometimes contacting spine head proximal boutons; Long-lived spinules contacted spine head distal presynaptic boutons and sometimes trafficked PSD fragments to their tips | Dissociated cortical neuron cultures of C57BL/6J mice; Somatosensory cortex from acute brain slices of one-month-old Thy1-YFP-H mice | Acute NMDAR activation to increase neuronal activity enhanced number and length of spinules, which extended to preferentially contact adjacent boutons; Kalirin-7 exogeneous expression increased spinules; Ca2+ chelator treatment decreased spinules | Most spinules were dynamic, small (<0.5 μm), short-lived (<60 s), associated with simple PSDs, and variously shaped; Fewer spinules were elongated, stable, long-lived (≥60 s), associated with complex PSDs, and shaped like filopodia, thin spines, or mushroom spines | Small, short-lived spinules explore their environment; Larger long-lived spinules form connections with spine head distal presynaptic terminals during increased activity; Structural plasticity and altered connectivity; Multi-synaptic spines |
| Campbell et al., eNeuro, 2020 | Postsynaptic spines or adjacent boutons and axons; Enveloped by presynaptic boutons and termed spinule-bearing boutons (SBBs) | Primary visual cortex of female and male ferrets | Prevalence of cortical SBBs in V1 increased across postnatal development; ~25% of excitatory boutons in late adolescent ferret V1 contained spinules | EM; Finger-like projections | Mechanism for extrasynaptic neuronal communication; Provide structural “anchors” to increase cortical synapse stability |
| Gore et al., Front. Synaptic Neurosci, 2022 | Adjacent excitatory axons and boutons, postsynaptic dendritic spines, or adjacent non-synaptic spines | Hippocampal CA1 stratum radiatum of adult rats | Adulthood; Ubiquitous at excitatory synapses | FIB-SEM; Thin, finger-like projections; Two subtypes included small clathrin-coated spinules, and larger non-clathrin coated spinules | Small spinules strengthen and stabilize synaptic connections or increase communication via trans-endocytosis; Large spinules increase extrasynaptic membrane interface for stability and communication |