Dendritic spikes in apical oblique dendrites of cortical layer 5 pyramidal neurons

Abstract

Dendritic spikes in layer 5 pyramidal neurons (L5PNs) play a major role in cortical computation. While dendritic spikes have been studied extensively in apical and basal dendrites of L5PNs, whether oblique dendrites, which ramify in the input layers of the cortex, also generate dendritic spikes is unknown. Here we report the existence of dendritic spikes in apical oblique dendrites of L5PNs. In silico investigations indicate that oblique branch spikes are triggered by brief, low-frequency action potential (AP) trains (~40 Hz) and are characterized by a fast sodium spike followed by activation of voltage-gated calcium channels. In vitro experiments confirmed the existence of oblique branch spikes in L5PNs during brief AP trains at frequencies of around 60 Hz. Oblique branch spikes offer new insights into branch-specific computation in L5PNs and may be critical for sensory processing in the input layers of the cortex.

Analyzing Branch‐specific Dendritic Spikes Using an Ultrafast Laser Scalpel

“…Other dendrites, such as the proximal oblique O#1, do not evoke a D-spike as observed by the absence of a temporally broad depolarization ( Figure 1E). In this particular L5PN model, branch-specific D-spikes are evoked only at two oblique dendrites: O#3 ( Figure 1D) and O#5 (data not shown) [21].…”

“…The procedure for numerical experiments is described in the Supplementary Methods 1. We slightly modified the L5PN model to shape the neuron's response closer to our empirical data [21]. Our experiments show that oblique branches of L5PNs are less excitable compared to the model.…”

“…We have recently reported that D-spikes also occur in apical oblique dendrites of L5PNs [20,21]. D-spikes in apical oblique branches are triggered by a low-frequency (f ≥ 60 Hz) train of action potentials (APs), which we initially investigated using a multi-compartment model of a L5PN and confirmed experimentally via functional calcium imaging [21]. As APs back-propagate to the dendritic tree, they activate VGCCs at the dendrite to generate a spike.…”

“…Although their work did not focus on D-spikes evoked in particular dendritic domains, their findings show that dendrotomy of the apical trunk of L5PNs reduced the overall excitability and the afterdepolarization (ADP) at the soma. While the ADP comes from multiple sources across the dendritic tree [25], it has been primarily associated with the recruitment of D-spikes in specific regions such as the nexus of the apical tuft [15,16] and oblique branches of L5PNs [21]. However, unlike the wide reach of a D-spike at the nexus that extends throughout the tuft, investigating spikes in select oblique branches requires identifying the specificity of spike generation.…”

“…Hence, we adopted a highly-targeted optical ablation approach using a tightly-focused ultrafast laser scalpel [26]. We evoked D-spikes in apical oblique dendrites [21] and observed the changes in the ADP profile following dendrotomy. Since dendrotomy via an ultrafast laser scalpel is an irreversible process, it would take a large number of experiments to draw neuro-physiological conclusions as to the extent of specificity of spike generation among oblique branches.…”