Synaptic mechanisms underlying the intense firing of neocortical layer 5B pyramidal neurons in response to cortico-cortical inputs

Alejandro Sempere-Ferràndez,Salvador Martínez,Emilio Geijo-Barrientos

doi:10.1007/s00429-019-01842-8

Abstract

In the neocortex, large layer 5B pyramidal neurons implement a high-density firing code. In contrast, other subtypes of pyramidal neurons, including those in layer 2/3, are functionally characterized by their sparse firing rate. Here, we investigate the synaptic basis of this behavior by comparing the properties of the postsynaptic responses evoked by cortical inputs in layer 5B and layer 2/3 pyramidal neurons in vitro. We demonstrate that a major determinant of the larger responsiveness of layer 5B with respect to layer 2/3 pyramidal neurons is the different properties in their inhibitory postsynaptic currents (IPSCs): layer 5B pyramidal neurons have IPSCs of lower amplitude and the temporal delay between the excitatory and inhibitory synaptic components is also larger in these cells. Our data also suggest that this difference depends on the lower gain of the cortical response of layer 5 parvalbumin-positive fast-spiking (PV-FS) interneurons with respect to PV-FS cells from layer 2/3. We propose that, while superficial PV-FS interneurons are well suited to provide a powerful feed-forward inhibitory control of pyramidal neuron responses, layer 5 PV-FS interneurons are mainly engaged in a feedback inhibitory loop and only after a substantial recruitment of surrounding pyramidal cells do they respond to an external input.

Highlights

A landmark of neocortical organization is its laminar arrangement (Lewis 1880), with neurons from different layers showing distinct genetic, morphologic and functional properties (Thomson and Lamy 2007)
We have studied the synaptic determinants of the responses of layer 2/3 and layer 5B pyramidal neurons in response to cortical inputs in slices of mice of 17–21 postnatal days
The postsynaptic potentials (PSPs) were larger in the L5BL pyramidal cell, which fired a burst of 2–4 action potentials in response to 200 and 500 μA, while in the L2/3 pyramidal neuron the PSPs were subthreshold for the three intensities tested

Summary

Introduction

A landmark of neocortical organization is its laminar arrangement (Lewis 1880), with neurons from different layers showing distinct genetic, morphologic and functional properties (Thomson and Lamy 2007). Electrophysiological recordings and calcium imaging in sensory, motor, and associative cortex in vivo have revealed that pyramidal neurons in layer 2/3 implement a sparse firing code (Beloozerova et al 2003a, b; Crochet and Petersen 2006; Sakata and Harris 2009; Sawinski et al 2009; Crochet et al 2011). Electrophysiological recordings in vitro have shown that in response to local inputs, layer 5 cells have a larger excitation to inhibition (E/I) balance than those in layer 2/3 (Adesnik and Scanziani 2010). Several studies indicate that superficial microcircuits are characterized by a potent feed-forward inhibitory input arising from PV-FS cells (Holmgren et al 2003; Mateo et al 2011; Avermann et al 2012), which could explain the lower E/I balance and sparse recruitment of layer 2/3 pyramidal neurons. Fewer reports have addressed the role of PV-FS inhibitory neurons in deeper layers, and a direct comparison with those in superficial layers is missing

Methods

Results

Conclusion