Robust emergence of sharply tuned place-cell responses in hippocampal neurons with structural and biophysical heterogeneities


Hippocampal pyramidal neurons sustain propagation of fast electrical signals and are electrotonically non-compact structures exhibiting cell-to-cell variability in their complex dendritic arborization. In this study, we demonstrate that sharp place-field tuning and several somatodendritic functional maps concomitantly emerge despite the presence of geometrical heterogeneities in these neurons. We establish this employing an unbiased stochastic search strategy involving thousands of models that spanned several morphologies and distinct profiles of dispersed synaptic localization and channel expression. Mechanistically, employing virtual knockout models (VKMs), we explored the impact of bidirectional modulation in dendritic spike prevalence on place-field tuning sharpness. Consistent with the prior literature, we found that across all morphologies, virtual knockout of either dendritic fast sodium channels or N-methyl-d-aspartate receptors led to a reduction in dendritic spike prevalence, whereas A-type potassium channel knockouts resulted in a non-specific increase in dendritic spike prevalence. However, place-field tuning sharpness was critically impaired in all three sets of VKMs, demonstrating that sharpness in feature tuning is maintained by an intricate balance between mechanisms that promote and those that prevent dendritic spike initiation. From the functional standpoint of the emergence of sharp feature tuning and intrinsic functional maps, within this framework, geometric variability was compensated by a combination of synaptic democracy, the ability of randomly dispersed synapses to yield sharp tuning through dendritic spike initiation, and ion-channel degeneracy. Our results suggest electrotonically non-compact neurons to be endowed with several degrees of freedom, encompassing channel expression, synaptic localization and morphological microstructure, in achieving sharp feature encoding and excitability homeostasis

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Last time updated on 16/03/2020

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