Asymmetric Voltage Attenuation in Dendrites Can Enable Hierarchical Heterosynaptic Plasticity

Area of Science:

• Neuroscience
• Computational Neuroscience
• Synaptic Plasticity

Background:

• Long-term synaptic plasticity is crucial for learning and memory.
• Cytosolic calcium concentrations (Ca2+) are key mediators of synaptic plasticity.
• Two primary sources of calcium influx at synapses are NMDA receptors and voltage-gated calcium channels (VGCCs).

Purpose of the Study:

• To investigate the interplay between NMDA receptors and VGCCs in mediating synaptic plasticity.
• To explore the heterosynaptic effects arising from the spatial distribution of synaptic inputs.
• To understand how dendritic electrical asymmetry influences the spatial targeting of heterosynaptic plasticity.

Main Methods:

• Development of a synaptic model incorporating calcium-based long-term plasticity.
• Implementation of two calcium sources: NMDA receptors and VGCCs.
• Conducting dendritic cable simulations to analyze calcium dynamics and plasticity.

Main Results:

• The interaction between NMDA receptors and VGCCs generates diverse heterosynaptic effects.
• Local NMDA spikes induce dendritic depolarization, activating VGCCs at non-activated spines, leading to heterosynaptic plasticity.
• Dendritic electrical asymmetry causes NMDA spikes to preferentially induce plasticity distally, creating hierarchical effects in branching dendrites.

Conclusions:

• The interplay of different calcium sources allows for complex synaptic plasticity mechanisms.
• Dendritic electrical asymmetry provides a basis for spatially targeted control of heterosynaptic plasticity.
• This study reveals sophisticated schemes for regulating synaptic plasticity based on input location and electrical properties.