Clustered Inputs Maximize Efficiency for Stable Place Field Encoding in Hippocampal Pyramidal Neurons
Year: 2025
Type: preprint
Abstract: The synaptic mechanisms driving feature selectivity in specific neuron types remains a fundamental and unresolved challenge in neuroscience. In hippocampal CA1 pyramidal neurons (PNs), the development of place selectivity, manifested as place fields, is believed to result from dendritic integration of spatially distributed inputs combined with behavioral time scale plasticity (BTSP). BTSP involves dendritic spikes that temporally regulate synaptic potentiation and depotentiation. However, the role of excitatory (E) and inhibitory (I) synaptic distributions in the emergence of place specificity in CA1 PNs remains unclear, due to the lack of detailed synaptic reconstructions in vivo. Here, we present full synaptic reconstructions from individual CA1 PNs in the mouse hippocampus, revealing that these neurons receive approximately 10,000-15,000 E synapses and 900-1,400 I synapses. Computational modeling of biologically relevant E and I synaptic distributions shows that spatial tuning is preserved with co-tuned, spatially clustered E synapses, but disrupted when E distributions are randomized. Moreover, synapse clustering has a different contribution to spatial tuning in apical vs. basal domains. Our results reveal a complex and finely-tuned interplay between presynaptic input patterns and the spatial organization of their postsynaptic targets in dictating neuronal output in CA1 PNs.
Authors: Simone Tasciotti, Daniel Maxim Iascone, Spyridon Chavlis, Luke Hammond, Yardena Katz, Attila Losonczy, Franck Polleux, Panayiota Poirazi
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Stavros Niarchos Foundation, Hellenic Foundation for Research and Innovation, National Institutes of Health, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, NextGenerationEU
Awards: Whole-neuron structural input mapping of SRGAP2 regulation of synaptic development, Dissecting the role of the dentate gyrus microcircuit to improve cognitive discrimination in aging and Alzheimer's Disease, G2649730223, Local Circuit Control of Rapid Plasticity and Tunable Ensemble Formation in the Hippocampus, G2971767340, G3356783348, Transformation of a metal center that is polymerizing by a ROMP mechanism to a Ziegler mechanism., Advanced simulation, analysis and interpretation of network structures in biological data, Coupling between circadian rhythms and redox signaling in stem cell differentiation and adult neurogenesis, G4036834266, G410473053, G4222550140, G434337789, G4412624445, G4664136842, G5894368506, Microcircuit, cellular and molecular dissection of impaired hippocampal function in a mouse model of the 22q11.2 deletion, Mechanisms of cognitive flexibility across primates, rodents and machines, A dendro-centric framework for learning optimization in biological and artificial systems, Control of Axon Initial Segment in Epilepsy, Development, Maintenance, and Human-Specific Evolution of Cortical Circuits
OpenAlex ID: W4410936382