Synaptic Plasticity in CA1 Pyramidal Dendrites Depends on Specific Input Patterns
Post by Amanda McFarlan
What's the science?
Pyramidal neurons in the brain receive many complex inputs, and these electrical signals are then integrated and propagated by dendrites to the cell body of the neuron. Although dendritic activity is known to be involved in long term potentiation (LTP), the classical Hebbian view of plasticity still considers the backpropagating action potential (propagation back towards the dendrites) to be critical for inducing LTP. However, recent studies have shown that local dendritic activity may play an important role in mediating synaptic plasticity. This week in the Journal of Neuroscience, Magό and colleagues used 2-photon glutamate uncaging to investigate the plasticity rules at proximal (near the neuronal cell body) and distal (far from the neuronal cell body) dendritic spines.
How did they do it?
The authors used 2-photon glutamate uncaging to activate dendritic spines in CA1 pyramidal neurons that were targeted for whole-cell recording in acute hippocampal slices from adult male rats. To investigate the plasticity rules at these dendritic spines, the authors first recorded baseline excitatory post-synaptic potentials (EPSPs) in response to asynchronous activation of either proximal or distal dendritic spines. Then, they applied an LTP induction protocol whereby specific clusters of proximal or distal dendritic spines were synchronously activated and recorded proximal and distal dendritic spine EPSPs to measure LTP-induced changes in synaptic function.
Next, the authors investigated whether dendritic spiking plays a role in inducing plasticity at proximal and distal dendritic spines. Dendritic spiking allows for non-linear amplification of electric inputs that are spatially and temporally correlated. To study this, they activated small clusters of either proximal or distal dendritic spines during the LTP induction while simultaneously inducing dendritic spiking. Then, they explored the spatial rules of plasticity at distal dendrites by applying the LTP induction protocol to distal dendritic spines that were spread out along the dendrite (rather than clustered together) with and without dendritic spiking. Finally, the authors investigated whether changes in plasticity in targeted clusters of dendritic spines induced heterosynaptic plasticity (when a change in synaptic strength in one neuron occurs following the activation of another neuron or pathway) in nearby spines.
What did they find?
The authors found that the activation of proximal dendritic spines resulted in robust and long-lasting LTP only when it was coupled with dendritic spiking, suggesting that inducing LTP at synapses located on proximal dendrites requires a large depolarization from a local or backpropagating action potential. Next, the authors revealed that unlike proximal dendritic spines, the coactivation of a few distal dendritic spines alone was sufficient to induce LTP when the spines were located close in proximity to one another. They also showed that LTP was induced in distal dendritic spines that were spread out along the dendrite when their activation was coupled with dendritic spiking. Additionally, they found that LTP was induced using a much lower stimulus number in distal dendritic spines when the activation of these spines was coupled with dendritic spiking. Together, these results suggest that dendritic spiking is not required for the induction of LTP in synapses located in the distal dendrite but can be beneficial for reducing the number of coincident activity events required for LTP induction and for allowing cooperativity between spatially distant dendritic spines. Finally, the authors determined that following the LTP induction and dendritic spiking, dendritic spines that were not directly targeted for activation, but that were in close proximity to activated spines, showed evidence of LTP. Wash-in experiments with blockers revealed that this effect was abolished when the NMDA receptor, as well as the MEK/ERK pathway (important for mediating local plasticity of GTPases), were inhibited. Together, these results suggest that the activation of nearby dendritic spines by dendritic spiking induces heterosynaptic plasticity that is mediated by NMDA receptor and MEK/ERK signaling.
What’s the impact?
This is the first study to show that several mechanisms are involved in facilitating LTP at dendritic spines. The authors found that the LTP is induced when distal dendritic spines close in proximity to one another are synchronously activated. Additionally, they revealed that dendritic spiking coupled with dendritic spine activation enables cooperativity between dendritic spines that are spatially distant as well as induces heterosynaptic plasticity at nearby synapses. Together, these findings provide insight into the many forms of plasticity that are occurring locally at the dendrite and are allowing neurons to store new information in the absence of somatic firing.
Magό et al. Synaptic Plasticity Depends on the Fine-Scale Input Pattern in Thin Dendrites of CA1 Pyramidal Neurons. Journal of Neuroscience (2020). Access the original scientific publication here.