{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:28:33Z","timestamp":1793237313887,"version":"4.5.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Dendritic spines are highly dynamic and changes in their density, size, and shape underlie structural synaptic plasticity in cognition and memory. Fine membranous protrusions of spines, termed dendritic spinules, can contact neighboring neurons or glial cells and are positively regulated by neuronal activity. Spinules are thinner than filopodia, variable in length, and often emerge from large mushroom spines. Due to their nanoscale, spinules have frequently been overlooked in diffraction-limited microscopy datasets. Until recently, our knowledge of spinules has been interpreted largely from single snapshots in time captured by electron microscopy. We summarize herein the current knowledge about the molecular mechanisms of spinule formation. Additionally, we discuss possible spinule functions in structural synaptic plasticity in the context of development, adulthood, aging, and psychiatric disorders. The literature collectively implicates spinules as a mode of structural synaptic plasticity and suggests the existence of morphologically and functionally distinct spinule subsets. A recent time-lapse, enhanced resolution imaging study demonstrated that the majority of spinules are small, short-lived, and dynamic, potentially exploring their environment or mediating retrograde signaling and membrane remodeling <jats:italic>via<\/jats:italic> trans-endocytosis. A subset of activity-enhanced, elongated, long-lived spinules is associated with complex PSDs, and preferentially contacts adjacent axonal boutons not presynaptic to the spine head. Hence, long-lived spinules can form secondary synapses with the potential to alter synaptic connectivity. Published studies further suggest that decreased spinules are associated with impaired synaptic plasticity and intellectual disability, while increased spinules are linked to hyperexcitability and neurodegenerative diseases. In summary, the literature indicates that spinules mediate structural synaptic plasticity and perturbations in spinules can contribute to synaptic dysfunction and psychiatric disease. Additional studies would be beneficial to further delineate the molecular mechanisms of spinule formation and determine the exact role of spinules in development, adulthood, aging, and psychiatric disorders.<\/jats:p>","DOI":"10.3389\/fnmol.2023.1059730","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T07:04:40Z","timestamp":1674198280000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Dendritic spinule-mediated structural synaptic plasticity: Implications for development, aging, and psychiatric disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Colleen R.","family":"Zaccard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Gippo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changiz","family":"Geula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Penzes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41572-021-00280-3","article-title":"Parkinson disease-associated cognitive impairment","volume":"7","author":"Aarsland","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1006\/neur.1996.0018","article-title":"Synaptic plasticity in the caudate nucleus of patients with Parkinson's disease","volume":"5","author":"Anglade","year":"1996","journal-title":"Neurodegeneration"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/nn.2462","article-title":"PIP3 controls synaptic function by maintaining AMPA receptor clustering at the postsynaptic membrane","volume":"13","author":"Arendt","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref4","first-page":"193","article-title":"Synaptic reorganizations in epileptic human and rat kainate hippocampus may contribute to feedback and feedforward excitation","volume":"9","author":"Babb","year":"1992","journal-title":"Epilepsy Res. Suppl."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/0166-2236(90)90135-W","article-title":"Brief seizure episodes induce long-term potentiation and mossy fibre sprouting in the hippocampus","volume":"13","author":"Ben-Ari","year":"1990","journal-title":"Trends Neurosci."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"123","DOI":"10.3389\/fnana.2014.00123","article-title":"Structural plasticity: mechanisms and contribution to developmental psychiatric disorders","volume":"8","author":"Bernardinelli","year":"2014","journal-title":"Front. Neuroanat."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3389\/fnana.2015.00013","article-title":"Deletion of KIBRA, protein expressed in kidney and brain, increases filopodial-like long dendritic spines in neocortical and hippocampal neurons in vivo and in vitro","volume":"9","author":"Blanque","year":"2015","journal-title":"Front. Neuroanat."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.conb.2007.04.009","article-title":"Do thin spines learn to be mushroom spines that remember?","volume":"17","author":"Bourne","year":"2007","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1002\/(SICI)1096-9861(19970901)385:3<385::AID-CNE4>3.0.CO;2-%23","article-title":"Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats","volume":"385","author":"Buckmaster","year":"1997","journal-title":"J. Comp. Neurol."},{"key":"ref10","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0426-19.2020","article-title":"Cortical presynaptic Boutons progressively engulf spinules as they mature","volume":"7","author":"Campbell","year":"2020","journal-title":"eNeuro"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0022-5320(72)80012-1","article-title":"Ultrastructure and synaptic relations in the optic lobe of the brain of Eledone and octopus","volume":"39","author":"Case","year":"1972","journal-title":"J. Ultrastruct. Res."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.15252\/embj.201488837","article-title":"Nanoscale segregation of actin nucleation and elongation factors determines dendritic spine protrusion","volume":"33","author":"Chazeau","year":"2014","journal-title":"EMBO J."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/sj.npp.1301559","article-title":"Synaptic plasticity: multiple forms, functions, and mechanisms","volume":"33","author":"Citri","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/S0092-8674(01)00579-7","article-title":"Remodeling of synaptic actin induced by photoconductive stimulation","volume":"107","author":"Colicos","year":"2001","journal-title":"Cells"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/nrn3680","article-title":"Wallerian degeneration: an emerging axon death pathway linking injury and disease","volume":"15","author":"Conforti","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1152\/jn.00585.2016","article-title":"Calcium dynamics and regulation in horizontal cells of the vertebrate retina: lessons from teleosts","volume":"117","author":"Country","year":"2017","journal-title":"J. Neurophysiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/hipo.10172","article-title":"Expression of long-term potentiation in aged rats involves perforated synapses but dendritic spine branching results from high-frequency stimulation alone","volume":"14","author":"Dhanrajan","year":"2004","journal-title":"Hippocampus"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"456857","DOI":"10.1155\/2013\/456857","article-title":"Bidirectional microglia-neuron communication in the healthy brain","volume":"2013","author":"Eyo","year":"2013","journal-title":"Neural Plast."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"8900","DOI":"10.1523\/JNEUROSCI.18-21-08900.1998","article-title":"Synaptogenesis via dendritic filopodia in developing hippocampal area CA1","volume":"18","author":"Fiala","year":"1998","journal-title":"J. Neurosci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"3027","DOI":"10.1073\/pnas.83.9.3027","article-title":"Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats","volume":"83","author":"Geinisman","year":"1986","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"968404","DOI":"10.3389\/fnsyn.2022.968404","article-title":"Synaptic spinules are reliable indicators of excitatory presynaptic Bouton size and strength and are ubiquitous components of excitatory synapses in CA1 hippocampus","volume":"14","author":"Gore","year":"2022","journal-title":"Front. Synaptic Neurosci."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1523\/JNEUROSCI.12-07-02685.1992","article-title":"Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation","volume":"12","author":"Harris","year":"1992","journal-title":"J. Neurosci."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1146\/annurev.ne.17.030194.002013","article-title":"Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function","volume":"17","author":"Harris","year":"1994","journal-title":"Annu. Rev. Neurosci."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/35104061","article-title":"Dendritic spines: structure, dynamics and regulation","volume":"2","author":"Hering","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/nrn2699","article-title":"Experience-dependent structural synaptic plasticity in the mammalian brain","volume":"10","author":"Holtmaat","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.conb.2015.12.004","article-title":"New insights on the role of microglia in synaptic pruning in health and disease","volume":"36","author":"Hong","year":"2016","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/0006-8993(91)90312-J","article-title":"Perforated and non-perforated synapses in rat neocortex: three-dimensional reconstructions","volume":"556","author":"Jones","year":"1991","journal-title":"Brain Res."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"10153","DOI":"10.1523\/JNEUROSCI.19-22-10153.1999","article-title":"Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats","volume":"19","author":"Jones","year":"1999","journal-title":"J. Neurosci."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"C641","DOI":"10.1152\/ajpcell.00222.2006","article-title":"Mitochondria and neuronal activity","volume":"292","author":"Kann","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.tins.2010.01.001","article-title":"Structural dynamics of dendritic spines in memory and cognition","volume":"33","author":"Kasai","year":"2010","journal-title":"Trends Neurosci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.neuroscience.2012.04.061","article-title":"Beyond counts and shapes: studying pathology of dendritic spines in the context of the surrounding neuropil through serial section electron microscopy","volume":"251","author":"Kuwajima","year":"2013","journal-title":"Neuroscience"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/j.1460-9568.1989.tb00771.x","article-title":"Absence of Wallerian degeneration does not hinder regeneration in peripheral nerve","volume":"1","author":"Lunn","year":"1989","journal-title":"Eur. J. Neurosci."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1002\/1096-9861(20010115)429:3<388::AID-CNE3>3.0.CO;2-I","article-title":"Expression of kalirin, a neuronal GDP\/GTP exchange factor of the trio family, in the central nervous system of the adult rat","volume":"429","author":"Ma","year":"2001","journal-title":"J. Comp. Neurol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.neuron.2011.08.017","article-title":"Regulation of AMPA receptor function by the human memory-associated gene KIBRA","volume":"71","author":"Makuch","year":"2011","journal-title":"Neuron"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"767.e8","DOI":"10.1016\/j.neuron.2018.04.011","article-title":"Filopodia conduct target selection in cortical neurons using differences in signal kinetics of a single kinase","volume":"98","author":"Mao","year":"2018","journal-title":"Neuron"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"13541","DOI":"10.1074\/jbc.M115.636746","article-title":"An N-terminal amphipathic helix binds Phosphoinositides and enhances Kalirin Sec14 domain-mediated membrane interactions","volume":"290","author":"Miller","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1126\/science.1129837","article-title":"Common Kibra alleles are associated with human memory performance","volume":"314","author":"Papassotiropoulos","year":"2006","journal-title":"Science"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1111\/j.1460-9568.1990.tb00433.x","article-title":"Evidence that the rate of Wallerian degeneration is controlled by a single autosomal dominant gene","volume":"2","author":"Perry","year":"1990","journal-title":"Eur. J. Neurosci."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.arr.2014.01.003","article-title":"Communication breakdown: the impact of ageing on synapse structure","volume":"14","author":"Petralia","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s12017-015-8358-6","article-title":"Structure, distribution, and function of neuronal\/synaptic Spinules and related Invaginating projections","volume":"17","author":"Petralia","year":"2015","journal-title":"NeuroMolecular Med."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s12017-017-8445-y","article-title":"Invaginating presynaptic terminals in neuromuscular junctions, photoreceptor terminals, and other synapses of animals","volume":"19","author":"Petralia","year":"2017","journal-title":"NeuroMolecular Med."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3389\/fnsyn.2018.00004","article-title":"Invaginating structures in mammalian synapses","volume":"10","author":"Petralia","year":"2018","journal-title":"Front. Synaptic Neurosci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1002\/cne.22573","article-title":"Three-dimensional synaptic ultrastructure in the dentate gyrus and hippocampal area CA3 in the Ts65Dn mouse model of down syndrome","volume":"519","author":"Popov","year":"2011","journal-title":"J. Comp. Neurol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S0166-2236(00)02118-4","article-title":"Rho proteins, mental retardation and the cellular basis of cognition","volume":"25","author":"Ramakers","year":"2002","journal-title":"Trends Neurosci."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"6166","DOI":"10.1073\/pnas.0501881102","article-title":"Glutamate induces the rapid formation of spine head protrusions in hippocampal slice cultures","volume":"102","author":"Richards","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0304-3940(99)00374-2","article-title":"Ultrastructural change of synapses of Betz cells in patients with amyotrophic lateral sclerosis","volume":"268","author":"Sasaki","year":"1999","journal-title":"Neurosci. Lett."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.neuron.2012.03.026","article-title":"Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner","volume":"74","author":"Schafer","year":"2012","journal-title":"Neuron"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/0006-8993(90)91654-Y","article-title":"Spinules in axospinous synapses of the rat dentate gyrus: changes in density following long-term potentiation","volume":"523","author":"Schuster","year":"1990","journal-title":"Brain Res."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"a005678","DOI":"10.1101\/cshperspect.a005678","article-title":"The postsynaptic organization of synapses","volume":"3","author":"Sheng","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1002\/(SICI)1096-9861(19980824)398:2<225::AID-CNE5>3.0.CO;2-2","article-title":"Critical assessment of the involvement of perforations, spinules, and spine branching in hippocampal synapse formation","volume":"398","author":"Sorra","year":"1998","journal-title":"J. Comp. Neurol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"4233","DOI":"10.1523\/JNEUROSCI.0287-04.2004","article-title":"Trans-endocytosis via spinules in adult rat hippocampus","volume":"24","author":"Spacek","year":"2004","journal-title":"J. Neurosci."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1146\/annurev-neuro-061010-113810","article-title":"The complement system: an unexpected role in synaptic pruning during development and disease","volume":"35","author":"Stephan","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"735919","DOI":"10.3389\/fnmol.2021.735919","article-title":"The curious anti-pathology of the Wld (s) mutation: paradoxical postsynaptic spine growth accompanies delayed presynaptic Wallerian degeneration","volume":"14","author":"Steward","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.1111\/j.1528-1157.1990.tb05859.x","article-title":"Experimental models of temporal lobe epilepsy: new insights from the study of kindling and synaptic reorganization","volume":"31","author":"Sutula","year":"1990","journal-title":"Epilepsia"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.neuroscience.2009.02.031","article-title":"Rapid turnover of spinules at synaptic terminals","volume":"160","author":"Tao-Cheng","year":"2009","journal-title":"Neuroscience"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/0040-8166(77)90006-4","article-title":"The synaptic spinule in the dendritic spine: electron microscopic study of the hippocampal dentate gyrus","volume":"9","author":"Tarrant","year":"1977","journal-title":"Tissue Cell"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1523\/JNEUROSCI.05-04-01016.1985","article-title":"Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats","volume":"5","author":"Tauck","year":"1985","journal-title":"J. Neurosci."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/46574","article-title":"LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite","volume":"402","author":"Toni","year":"1999","journal-title":"Nature"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"6245","DOI":"10.1523\/JNEUROSCI.21-16-06245.2001","article-title":"Remodeling of synaptic membranes after induction of long-term potentiation","volume":"21","author":"Toni","year":"2001","journal-title":"J. Neurosci."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.freeradbiomed.2017.09.025","article-title":"Dendritic spine pathology and thrombospondin-1 deficits in down syndrome","volume":"114","author":"Torres","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"e1000527","DOI":"10.1371\/journal.pbio.1000527","article-title":"Microglial interactions with synapses are modulated by visual experience","volume":"8","author":"Tremblay","year":"2010","journal-title":"PLoS Biol."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"16064","DOI":"10.1523\/JNEUROSCI.4158-11.2011","article-title":"The role of microglia in the healthy brain","volume":"31","author":"Tremblay","year":"2011","journal-title":"J. Neurosci."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"11040","DOI":"10.1523\/JNEUROSCI.3122-12.2013","article-title":"PIP(3) regulates spinule formation in dendritic spines during structural long-term potentiation","volume":"33","author":"Ueda","year":"2013","journal-title":"J. Neurosci."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.tins.2012.11.007","article-title":"Microglia: actively surveying and shaping neuronal circuit structure and function","volume":"36","author":"Wake","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1038\/s41467-018-03566-5","article-title":"Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction","volume":"9","author":"Weinhard","year":"2018","journal-title":"Nat. Commun."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/S0022-5320(70)80004-1","article-title":"Ultrastructure of synapses in a primitive coelenterate","volume":"32","author":"Westfall","year":"1970","journal-title":"J. Ultrastruct. Res."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/cne.901190303","article-title":"An electron microscopic study of the stratum radiatum of the rat hippocampus (regio superior, CA 1) with particular emphasis on synaptology","volume":"119","author":"Westrum","year":"1962","journal-title":"J. Comp. Neurol."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1038\/npp.2015.203","article-title":"Impact of KIBRA polymorphism on memory function and the hippocampus in older adults","volume":"41","author":"Witte","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.it.2015.08.008","article-title":"Microglia: dynamic mediators of synapse development and plasticity","volume":"36","author":"Wu","year":"2015","journal-title":"Trends Immunol."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/j.neuron.2007.10.005","article-title":"Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines","volume":"56","author":"Xie","year":"2007","journal-title":"Neuron"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1038\/nn.4370","article-title":"Selective synaptic remodeling of amygdalocortical connections associated with fear memory","volume":"19","author":"Yang","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"99","DOI":"10.26599\/BSA.2018.2018.9050012","article-title":"Changes of synaptic structures associated with learning","volume":"4","author":"Yang","year":"2018","journal-title":"Mem. Dis. Brain Sci. Adv."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"100427","DOI":"10.1016\/j.xpro.2021.100427","article-title":"Protocol for live enhanced resolution confocal imaging of dendritic spinule dynamics in primary mouse cortical neuron culture","volume":"2","author":"Zaccard","year":"2021","journal-title":"STAR Protoc."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"522.e6","DOI":"10.1016\/j.neuron.2020.04.025","article-title":"Rapid 3D enhanced resolution microscopy reveals diversity in dendritic Spinule dynamics, regulation, and function","volume":"107","author":"Zaccard","year":"2020","journal-title":"Neuron"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1002\/(SICI)1096-9861(19990322)405:4<472::AID-CNE3>3.0.CO;2-P","article-title":"Ultrastructural localization of dynorphin in the dentate gyrus in human temporal lobe epilepsy: a study of reorganized mossy fiber synapses","volume":"405","author":"Zhang","year":"1999","journal-title":"J. Comp. Neurol."}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2023.1059730\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T07:04:45Z","timestamp":1674198285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2023.1059730\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,20]]},"references-count":75,"alternative-id":["10.3389\/fnmol.2023.1059730"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2023.1059730","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,20]]},"article-number":"1059730"}}