Network-neuron interactions underlying sensory responses of layer 5 pyramidal tract neurons in barrel cortex

PLoS Comput Biol. 2024 Apr 16;20(4):e1011468. doi: 10.1371/journal.pcbi.1011468. eCollection 2024 Apr.

Abstract

Neurons in the cerebral cortex receive thousands of synaptic inputs per second from thousands of presynaptic neurons. How the dendritic location of inputs, their timing, strength, and presynaptic origin, in conjunction with complex dendritic physiology, impact the transformation of synaptic input into action potential (AP) output remains generally unknown for in vivo conditions. Here, we introduce a computational approach to reveal which properties of the input causally underlie AP output, and how this neuronal input-output computation is influenced by the morphology and biophysical properties of the dendrites. We demonstrate that this approach allows dissecting of how different input populations drive in vivo observed APs. For this purpose, we focus on fast and broadly tuned responses that pyramidal tract neurons in layer 5 (L5PTs) of the rat barrel cortex elicit upon passive single whisker deflections. By reducing a multi-scale model that we reported previously, we show that three features are sufficient to predict with high accuracy the sensory responses and receptive fields of L5PTs under these specific in vivo conditions: the count of active excitatory versus inhibitory synapses preceding the response, their spatial distribution on the dendrites, and the AP history. Based on these three features, we derive an analytically tractable description of the input-output computation of L5PTs, which enabled us to dissect how synaptic input from thalamus and different cell types in barrel cortex contribute to these responses. We show that the input-output computation is preserved across L5PTs despite morphological and biophysical diversity of their dendrites. We found that trial-to-trial variability in L5PT responses, and cell-to-cell variability in their receptive fields, are sufficiently explained by variability in synaptic input from the network, whereas variability in biophysical and morphological properties have minor contributions. Our approach to derive analytically tractable models of input-output computations in L5PTs provides a roadmap to dissect network-neuron interactions underlying L5PT responses across different in vivo conditions and for other cell types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials* / physiology
  • Animals
  • Computational Biology
  • Computer Simulation
  • Dendrites / physiology
  • Models, Neurological*
  • Nerve Net / physiology
  • Pyramidal Cells / physiology
  • Pyramidal Tracts / physiology
  • Rats
  • Somatosensory Cortex* / cytology
  • Somatosensory Cortex* / physiology
  • Synapses / physiology
  • Vibrissae / physiology

Grants and funding

Funding was provided by the European Research Council (ERC; grants 633428 and 101069192 to MO), the German Research Foundation (DFG; grants SFB 1089 and SPP 2041 to MO), the German Federal Ministry of Education and Research (BMBF; grant 01IS18052 to MO), the Neuroscience Network North Rhine-Westphalia grant iBehave (to MO), and the NWO Open Competition grant (ENW-M2, project OCENW.M20.285, to CK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.