I'm looking for resources or any information about the formation of dendritic spines and synaptogenesis, especially in relation to how new connections are formed on a daily basis.

Does the electrotonic signalling along the axons and through the spines cause new connections to be made based on some kind of spatial condition (maybe an electrical or chemical attraction), or is there some larger heuristic here?


3 Answers 3


Spine formation (spinogenesis) is almost certainly due to chemical, rather than electrical, signalling between neurons. Although there are exceptions (gap junctions, for one), most forms of inter-cellular communication are mediated by chemicals released by one cell and detected by another. You are right that the cues for synaptogenesis are probably localized (the "spatial condition"), but I'm willing to bet the farm that those local cues are chemical in nature.

A recent paper from Kwon and Sabatini (2011) shows that local release of the neurotransmitter glutamate is sufficient to cause a functional spine to form. Glutamate receptors on the dendrite detect the glutamate and a spine forms (within seconds). At least under these conditions, the presynaptic machinery isn't required at all! Of course, in a less reduced preparation, electrical activity in the axon will signal the glutamate release from the presynaptic side. Thus, in this case, spine formation is activity-dependent but is mediated by chemical cues.

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    $\begingroup$ Please note that the phenomenon Kwon and Sabatini describe only manifests itself in brain slices from very young animals and not at all in brain slices from adults. $\endgroup$
    – vkehayas
    Commented Sep 3, 2017 at 12:17

Dendritic spines are thought to grow and recede under LTP and LTD, respectively. See (Bosch and Hayoshi 2011) for a review.

From there, much of the synaptogenesis occurs due to surface molecules present both on the dendrite and the presynaptic axon in the growth cone. Localization and guidance are achieved through gradients of growth factors in the developing nervous system See (Kolodkin and Tessier-Lavigne 2011) for a review of all of these mechanics.

How this maps back onto the human CNS and thinking/learning/memorizing is still up for debate, but some of these mechanisms must have been preserved in higher species.


Bosch M, Hayashi Y. (2012) Structural plasticity of dendritic spines. Curr Opin Neurobiol.,22(3):383-8. (Epub 2011 Sep 28).

Kolodkin AL, Tessier-Lavigne M. (2011). Mechanisms and molecules of neuronal wiring: a primer. Cold Spring Harb Perspect Biol., 3(6). [DOI]

  • $\begingroup$ Although both classes of phenomena are relevant for synaptic and spine dynamics: 1) LTP and LTD are classically thought to require a pre-existing synapse, 2) what happens in development may be different than what happens in adult life. $\endgroup$
    – vkehayas
    Commented Sep 3, 2017 at 17:57
  • $\begingroup$ I think the insightful comments you've made on my answer and the one above really are worthy of a new answer. I've been out of the neuroscience game for almost 10 years now, so I definitely defer to your expertise! Thanks for commenting. $\endgroup$
    – jonsca
    Commented Sep 3, 2017 at 21:52

Two classes of factors contributing to spinogenesis have been described in the literature, based on whether they can be considered extrinsic or intrinsic to the dendrite (my classification). Here is a shortlist of evidence in favour of either:

A. Extrinsic:

  1. the presence of extracellular glutamate facilitates spine formation in tissue from very young mice (Richards et al., 2005; Kwon and Sabatini, 2011)

  2. new spines preferentially form towards boutons with pre-existing synaptic contacts (Toni et al., 1999, 2007; Knott et al., 2006; Nägerl et al., 2007)

B. Intrinsic:

  1. new spines tend to form away from pre-existing spines on the dendrite (Fu et al. 2012)

  2. dendrites with lower spine densities display a higher degree of spinogenesis (Holtmaat et al. 2005)

A proposed mechanism extrinsic to the dendrite that can lead to spinogenesis is glutamate spill-over. Conceivable mechanisms intrinsic to the dendrite that can control spinogenesis can be the competition for resources (structural proteins, mRNA etc).

Dendrites of pyramidal cells in some areas of the cortex and the hippocampus exhibit a relatively high turn-over of spine formation and elimination (Holtmaat et al. 2005, Attardo et al. 2015), at least as compared to axonal boutons (e.g. de Paola 2006). Whereas some of these new spines stabilize, many disappear soon after their formation. This indicates that, at least in part, their creation is not fully specified by the existence of a pre-synaptic partner, if we assume that the pre-synaptic partner continues to "attract" them (and that's a big if). The relative independence of spinogenesis from presynaptic activity is further corroborated by the fact that most new spines lack a synapse (Knott et al., 2006).

It appears, then, that dendrites over-produce spines in order to sample their environment for potential synaptic partners. The advantage of such a mechanism can be seen when considering the potential wiring diagram changes that neurons can achieve with such relatively cost-less microscopic changes (Stepanyants et al. 2002). It is unclear at the moment at what point between spinogenesis and synapse formation presynaptic activity becomes an influencing factor in the intact adult brain. A theory incorporating the existing information on spinogenesis is forthcoming.


  • Attardo A, Fitzgerald JE, Schnitzer MJ. (2015) Impermanence of dendritic spines in live adult CA1 hippocampus. Nature, 523(7562), 592-596. https://doi.org/10.1038/nature14467

  • De Paola, V., Holtmaat, A., Knott, G., Song, S., Wilbrecht, L., Caroni, P., & Svoboda, K. (2006). Cell Type-Specific Structural Plasticity of Axonal Branches and Boutons in the Adult Neocortex. Neuron, 49(6), 861–875. https://doi.org/10.1016/j.neuron.2006.02.017

  • Fu, M., Yu, X., Lu, J., & Zuo, Y. (2012). Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo. Nature, 483(7387), 92–95. https://doi.org/10.1038/nature10844

  • Holtmaat, A. J. G. D., Trachtenberg, J. T., Wilbrecht, L., Shepherd, G. M., Zhang, X., Knott, G. W., & Svoboda, K. (2005). Transient and Persistent Dendritic Spines in the Neocortex In Vivo. Neuron, 45(2), 279–291. https://doi.org/10.1016/j.neuron.2005.01.003

  • Knott, G. W., Holtmaat, A., Wilbrecht, L., Welker, E., & Svoboda, K. (2006). Spine growth precedes synapse formation in the adult neocortex in vivo. Nature Neuroscience, 9(9), 1117–1124. https://doi.org/10.1038/nn1747

  • Kwon, H.-B., & Sabatini, B. L. (2011). Glutamate induces de novo growth of functional spines in developing cortex. Nature, 474(7349), 100–104. https://doi.org/10.1038/nature09986

  • Nägerl, U. V., Köstinger, G., Anderson, J. C., Martin, K. A. C., & Bonhoeffer, T. (2007). Protracted synaptogenesis after activity-dependent spinogenesis in hippocampal neurons. The Journal of Neuroscience, 27(30), 8149–56. https://doi.org/10.1523/JNEUROSCI.0511-07.2007

  • Richards, D. A., Mateos, J. M., Hugel, S., de Paola, V., Caroni, P., Gahwiler, B. H., & McKinney, R. A. (2005). Glutamate induces the rapid formation of spine head protrusions in hippocampal slice cultures. Proceedings of the National Academy of Sciences, 102(17), 6166–6171. https://doi.org/10.1073/pnas.0501881102

  • Stepanyants, A., Hof, P. R., & Chklovskii, D. B. (2002). Geometry and structural plasticity of synaptic connectivity. Neuron, 34(2), 275–88. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11970869

  • Toni, N., Buchs, P. A., Nikonenko, I., Bron, C. R., & Muller, D. (1999). LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature, 402(6760), 421–5. https://doi.org/10.1038/46574

  • Toni, N., Teng, E. M., Bushong, E. a, Aimone, J. B., Zhao, C., Consiglio, A., … Gage, F. H. (2007). Synapse formation on neurons born in the adult hippocampus. Nature Neuroscience, 10(6), 727–734. https://doi.org/10.1038/nn1908


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