Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo

Abstract

Summary Many lines of evidence suggest that memory in the mammalian brain is stored with distinct spatiotemporal patterns1,2. Despite recent progresses in identifying neuronal populations involved in memory coding3–5, the synapse-level mechanism is still poorly understood. Computational models and electrophysiological data have shown that functional clustering of synapses along dendritic branches leads to nonlinear summation of synaptic inputs and greatly expands the computing power of a neural network6–10. However, whether neighboring synapses are involved in encoding similar memory and how task-specific cortical networks develop during learning remain elusive. Using transcranial two-photon microscopy11, we followed apical dendrites of layer 5 (L5) pyramidal neurons in the motor cortex while mice practiced novel forelimb skills. Here we show that a third of new dendritic spines (postsynaptic structures of most excitatory synapses) formed during the acquisition phase of learning emerge in clusters, and the majority of such clusters are neighboring spine pairs. These clustered new spines are more likely to persist throughout prolonged learning sessions and even long after training stops, compared to non-clustered counterparts. Moreover, formation of new spine clusters requires repetition of the same motor task, and the emergence of succedent new spine(s) accompanies the strengthening of the first new spine in the cluster. We also show that under control conditions new spines appear to avoid existing stable spines, rather than being uniformly added along dendrites. However, succedent new spines in clusters overcome such a spatial constraint and form in close vicinity to neighboring stable spines. Our findings suggest that clustering of new synapses along dendrites is induced by repetitive activation of the cortical circuitry during learning, providing a structural basis for spatial coding of motor memory in the mammalian brain.

Increased axonal bouton dynamics in the aging mouse cortex

“…Long-term rather than short-term changes in synaptic weight may be at the basis of memory encoding (41). Indeed changes in the volume of spine heads have been measured successfully in vivo both in normal (22) and altered (14,23,40) sensoryexperience paradigms and can correlate with functional changes. We find that even over extensive periods of time EPBs undergo substantial volume fluctuations (Ag 4-d intensity ratio: 42%; range, 0-618%; YA 4-d intensity ratio, 36%; range, 0-383%) comparable to those in dendritic spines in vivo (14,22) and in vitro (42).…”

“…Stabilization of newly formed dendritic spines in response to potentiation, novel experience, or learning is associated with a small increase in the average volume of the spine head both in vitro (39) and in vivo (40). Current research on the mechanisms of learning and memory has highlighted the importance of such stabilization of new spines together with concomitant elimination of previously existing ones.…”

A metaplasticity view of the interaction between homeostatic and Hebbian plasticity

“…Indeed, neighbouring synapses tend to share similar activity pattern [65,143]. Likewise, experience-induced synaptic changes also tend to exhibit highly structured spatial patterns favouring branch-based organization [144][145][146][147]. It will be of interest to investigate whether local homeostatic plasticity mechanisms contribute to the spatial organization of both synaptic and structural plasticity.…”

Evaluating Sparse Codes on Handwritten Digits

“…In the original ASP algorithm [19] the synapse permanence values have a potential range of 0 to 1 with the threshold set at 0.2 and initial permanences bound to be within 0.1 of the threshold. We use these values in our current study (see lines [4][5].…”