Synaptic Plasticity in Clustered Dendritic Synapses on a Hippocampal CA1 Pyramidal Neuron

Abstract

Background and aim: Synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), has been believed to underlie the biological basis of learning and memory in the brain. In the hippocampal CA1 area, Schaffer collateral-pyramidal cell synapses can undergo NMDAdependent LTP and LTD following high or low neuronal activity, respectively. The aim of this study was to evaluate the effect of the synaptic cluster properties on synaptic plasticity in a CA1 pyramidal neuron using a computational modeling approach. Materials and methods: We used a detailed compartmental model of a hippocampal CA1 pyramidal neuron (Migliore et al., PLOS Comp Biology 2018) and a NMDAr-dependent voltage-based model of synaptic plasticity to study the development of synaptic strengths in the individual Shaffer collateral synapses clustered or distributed randomly across the stratum radiatum region of the cell dendrites. Fifty synapses were stimulated simultaneously applying the protocols most widely used in experimental studies of synaptic plasticity: low-frequency (LF) stimulation at 1 Hz for 900 s for LTD induction and high-frequency (HF) continuous 100 Hz tetanization for 1 s repeated at 1 s interval for LTP induction. Results: Spatially clustered synapses (cluster radius 20 μm) underwent LTP following the HF stimulation and LTD after the LF stimulation, with 76% and 74% of synapses having been potentiated or weakened, respectively. Increased radius of the synaptic cluster (50 μm) promoted LTD induction for both HF and LF stimulation protocols, while the randomly distributed synapses remained unmodified. Conclusions: Structural organization of the multiple excitatory synaptic inputs shapes synaptic modifications in a CA1 pyramidal neuron.