Burst control: Synaptic conditions for burst generation in cortical layer 5 pyramidal neurons

Abstract

The output of neocortical layer 5 pyramidal cells (L5PCs) is expressed by a train of single spikes with intermittent bursts of multiple spikes at high frequencies. The bursts are the result of nonlinear dendritic properties, including Na+, Ca2+, and NMDA spikes, that interact with the ~10,000 synapses impinging on the neuron’s dendrites. Output spike bursts are thought to implement key dendritic computations, such as coincidence detection of bottom-up inputs (arriving mostly at the basal tree) and top-down inputs (arriving mostly at the apical tree). In this study we used a detailed nonlinear model of L5PC receiving excitatory and inhibitory synaptic inputs to explore the conditions for generating bursts and for modulating their properties. We established the excitatory input conditions on the basal versus the apical tree that favor burst and show that there are two distinct types of bursts. Bursts consisting of 3 or more spikes firing at < 200 Hz, which are generated by stronger excitatory input to the basal versus the apical tree, and bursts of ~2-spikes at ~250 Hz, generated by prominent apical tuft excitation. Localized and well-timed dendritic inhibition on the apical tree differentially modulates Na+, Ca2+, and NMDA spikes and, consequently, finely controls the burst output. Finally, we explored the implications of different burst classes and respective dendritic inhibition for regulating synaptic plasticity.

Aging-Dependent Altered Transcriptional Programs Underlie Activity Impairments in Human C9orf72-Mutant Motor Neurons

“…Together with the altered ability of firing synchronized bursts, suggesting synaptic imbalance ( Leleo and Segev, 2021 ), the early hyperactivity detected in ALS C9orf72 cultures was also matched by increased expression of synaptic transcripts and in line with the up-regulation of GluR1 at DIV17 detected by Shi and colleagues in C9orf72-mutant iMN (directly converted from fibroblasts; Shi et al, 2019 ). Though this early upregulation might appear in discordance with previously described reduced levels of synaptic genes in ALS MN ( Sareen et al, 2013 ; Hall et al, 2017 ; Catanese et al, 2021 ; Mehta et al, 2021 ), this seems to be related to the maturation state investigated.…”

The impact of Hodgkin–Huxley models on dendritic research

“…For example, the model could replicate the impact of dendritic and perisomatic inhibition on NMDA spike threshold and the subsequent somatic spike amplitude, as seen through GABA iontophoresis experiments (Jadi et al, 2012). Similar predictions were generated by models of neocortical L5 thick-tufted cells, whereby sodium, calcium and NMDA spikes were modulated by space-and time-specific apical dendrite inhibition, allowing for the fine control of bursting and synaptic plasticity (Leleo & Segev, 2021).…”

Context-sensitive processing in a model neocortical pyramidal cell with two sites of input integration

“…On the other hand, dendritic calcium spikes are controlled by inhibitory interneurons that target the apical tuft dendrites, affecting calcium spike initiation, or the apical trunk, affecting their transmission to the soma [43, 44]. [45] used detailed computer simulations of a layer 5 pyramidal cell to explore the spatio-temporal effects of inhibition on dendritic spiking and subsequent burst firing.…”