Heterosynaptic Structural Plasticity on Local Dendritic Segments of Hippocampal CA1 Neurons

Abstract

SUMMARY Competition between synapses contributes to activity-dependent refinement of the nervous system during development. Does local competition between neighboring synapses drive circuit remodeling during experience-dependent plasticity in the cerebral cortex? Here, we examined the role of activity-mediated competitive interactions in regulating dendritic spine structure and function on hippocampal CA1 neurons. We found that high-frequency glutamatergic stimulation at individual spines, which leads to input-specific synaptic potentiation, induces shrinkage and weakening of nearby unstimulated synapses. This heterosynaptic plasticity requires potentiation of multiple neighboring spines, suggesting that a local threshold of neural activity exists beyond which inactive synapses are punished. Notably, inhibition of calcineurin, IP3Rs, or group I mGluRs blocked heterosynaptic shrinkage without blocking structural potentiation, and inhibition of CaMKII blocked structural potentiation without blocking heterosynaptic shrinkage. Our results support a model in which activity-induced shrinkage signal, and not competition for limited structural resources, drives heterosynaptic structural and functional depression during neural circuit refinement.

Spontaneous Activity Drives Local Synaptic Plasticity In Vivo

“…Since previous studies have shown that spontaneous activity is necessary for the spatial clustering of co-active synapses (Kleindienst et al, 2011;Takahashi et al, 2012), we expected to find either a local plasticity mechanism for potentiation of synapses that are often co-active with their neighbors or for depression of locally desynchronized synapses. In fact, evidence for cooperation and competition among neighboring synapses, at least on longer time scales (min), has been reported previously (Frey and Morris, 1997;Harvey and Svoboda, 2007;Oh et al, 2015;review: Winnubst and Lohmann, 2012). Here, we find that synaptic clustering likely arises through a ''punishing'' plasticity rule: synapses that are only rarely co-active with neighboring synapses become less reliable and their transmission frequency decreases.…”

Hebbian plasticity requires compensatory processes on multiple timescales

“…Second, it is compensatory because it ensures stability by effectively enforcing a constraint on the afferent synaptic weights [10,57]. Biologically, such a heterosynaptic effect could be obtained, for instance, when synapses have to compete for a shared resource [57,85] or send chemical signals to each other [86]. …”

Clustered structural and functional plasticity of dendritic spines

“…This phenomenon is believed to help bind behaviorally relevant information on sub-compartments of dendrites. Another research used high-frequency glutamate uncaging to potentiate synapses of cultured hippocampal CA1 neurons (Oh et al, 2015). Interestingly, if multiple synapses on neighboring spines (≥6) are potentiated simultaneously, the inactive synapse within the cluster weakens and shrinks (see Fig.…”