Branch-specific dendritic Ca2+ spikes cause persistent synaptic plasticity

Abstract

The brain has an extraordinary capacity for memory storage, but how it stores new information without disrupting previously acquired memories remains unknown. Here we show that different motor learning tasks induce dendritic Ca2+ spikes on different apical tuft branches of individual layer V pyramidal neurons in the mouse motor cortex. These task-related, branch-specific Ca2+ spikes cause long-lasting potentiation of postsynaptic dendritic spines active at the time of spike generation. When somatostatin-expressing interneurons are inactivated, different motor tasks frequently induce Ca2+ spikes on the same branches. On those branches, spines potentiated during one task are depotentiated when they are active seconds before Ca2+ spikes induced by another task. Concomitantly, increased neuronal activity and performance improvement after learning one task are disrupted when another task is learned. These findings indicate that dendritic-branch-specific generation of Ca2+ spikes is crucial for establishing long-lasting synaptic plasticity, thereby facilitating information storage associated with different learning experiences.

Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling

“…Importantly, in some cases, the dendritic depolarizing event responsible for LTP induction has been identified both in slice experiments and in vivo [13,[15][16][17]. These studies point to the importance of branch-specific long-duration spikes mediated by NMDA channels.…”

“…It is therefore now clear that STDP, a process that assumes that only Na spikes determine LTP/LTD, is an incorrect description of plasticity. Given how easy it is to observe Na spikes by extracellular recording, the conclusion that such spikes are not critical for synaptic plasticity is unfortunate; recording NMDA spikes in dendrites is far more difficult but possible, even in vivo [17].…”

Integrating Hebbian and homeostatic plasticity: the current state of the field and future research directions

“…Homeostatic mechanisms can be implemented at the level of individual synapses [101], dendritic branches [66,[102][103][104][105], single cells [5,59] and the network [29], but obviously the interactions between these spatial scales will play an important role in overall firing rate homeostasis. For example, if the activity at all individual synapses is homeostatically regulated, then activity in dendritic branches, single cells and the network would be affected (and somewhat regulated) by that local regulation.…”

Overcoming catastrophic forgetting in neural networks

“…Recent evidence suggests that the mammalian brain may avoid catastrophic forgetting by protecting previously acquired knowledge in neocortical circuits (11)(12)(13)(14). When a mouse acquires a new skill, a proportion of excitatory synapses are strengthened; this manifests as an increase in the volume of individual dendritic spines of neurons (13).…”