Postnatal Development of Intrinsic and Synaptic Properties Transforms Signaling in the Layer 5 Excitatory Neural Network of the Visual Cortex

Abstract

Information flow in neocortical circuits is regulated by two key parameters: intrinsic neuronal properties and the short-term activitydependent plasticity of synaptic transmission. Using multineuronal whole-cell voltage recordings, we characterized the postnatal maturation of the electrophysiological properties and short-term plasticity of excitatory synaptic transmission between pairs of layer 5 (L5) pyramidal neurons (n ϭ 158) in acute slices of rat visual cortex over the first postnatal month. We found that the intrinsic and synaptic properties of L5 pyramidal neurons develop in parallel. Before postnatal day 15 (P15), intrinsic electrophysiological properties were tuned to low-frequency operation, characterized by high apparent input resistance, a long membrane time constant, and prolonged somatic action potentials. Unitary excitatory synaptic potentials were of large amplitude (P11-P15; median, 514 V), but showed pronounced use-dependent depression during prolonged regular and physiologically relevant presynaptic action potential firing patterns. In contrast, in mature animals we observed a developmental decline of the peak amplitude of unitary EPSPs (P25-P29; median, 175 V) paralleled by a decrease in apparent input resistance, membrane time constant, and somatic action potential duration. Notably, synaptic signaling of complex action potential firing patterns was also transformed, with P25-P29 connections faithfully signaling action potential trains at frequencies up to 40 Hz (1st to 50th action potential ratio, 0.91 Ϯ 0.12). Postnatal refinement of intrinsic properties and short-term plasticity therefore transforms the capacity of the L5 excitatory neural network of the visual cortex to generate and process patterns of action potential firing and contribute to network activity.

Electrophysiological properties of genetically identified subtypes of layer 5 neocortical pyramidal neurons: Ca2+ dependence and differential modulation by norepinephrine

“…RMP was measured immediately after entering whole cell mode. We found that the average RMP of layer 2/3 pyramidal cells was significantly more negative than either of the layer 5 subtypes (see also Breton and Stuart 2009;Etherington and Williams 2011;Higgs et al 2006;Larkman and Mason 1990), and etv1 cells had significantly more negative RMPs than glt cells (Fig. 2B, inset).…”

Electrophysiological Profiles of Induced Neurons Converted Directly from Adult Human Fibroblasts Indicate Incomplete Neuronal Conversion

“…The early postnatal development of the brain is of critical importance to assure correct wiring and firing of neuronal circuits in later life. Several studies have described postnatal changes in electrophysiological properties in a variety of rodent brain structures, including hippocampal, cortical, thalamic, and cerebellar brain areas (Belleau and Warren, 2000;Cui et al, 2010;Etherington and Williams, 2011;Kinnischtzke et al, 2012;Koppensteiner et al, 2014;McCormick and Prince, 1987;McKay and Turner, 2005;Pirchio et al, 1997;Spigelman et al, 1992;Tyzio et al, 2003). Thus, a reliable method to investigate the extent of neuronal differentiation and functionality of transdifferentiated neurons is the measurement of their electrophysiological properties.…”

Developmental Emergence of Sparse Coding: A Dynamic Systems Approach

“…To study the developmental states of visual cortical networks from before to after eye-opening, we selected four postnatal days (P) for modelling: P3 (period of physiological blindness), P10 (a few days before eye-opening), P14 (the day after eye-opening) and P20 (a few days after eye-opening) 3 . During this period, immature networks not only undergo the sparsification process but also a dramatic development in intrinsic neuronal and STP properties 10,12 ; see Table 1 and Supplementary Methods. To derive the results, we used system dynamics methods described in the Methods section (see also Supplementary Methods).…”

“…Strikingly, the time period of development during which sparsification occurs coincides with major changes in both intrinsic neuronal and synaptic properties. These include, for example, a profound decline in membrane resistance 2,10 , a steep increase in the number/density of both GABAergic and glutamatergic synapses 11,12 , an acceleration of the kinetics of postsynaptic currents 12 as well as pronounced changes in short-term synaptic plasticity 10,12 .…”