The Role of Hub Neurons in Modulating Cortical Dynamics

Abstract

Many neurodegenerative diseases are associated with the death of specific neuron types in particular brain regions. What makes the death of specific neuron types particularly harmful for the integrity and dynamics of the respective network is not well understood. To start addressing this question we used the most up-to-date biologically realistic dense neocortical microcircuit (NMC) of the rodent, which has reconstructed a volume of 0.3 mm3 and containing 31,000 neurons, ∼37 million synapses, and 55 morphological cell types arranged in six cortical layers. Using modern network science tools, we identified hub neurons in the NMC, that are connected synaptically to a large number of their neighbors and systematically examined the impact of abolishing these cells. In general, the structural integrity of the network is robust to cells’ attack; yet, attacking hub neurons strongly impacted the small-world topology of the network, whereas similar attacks on random neurons have a negligible effect. Such hub-specific attacks are also impactful on the network dynamics, both when the network is at its spontaneous synchronous state and when it was presented with synchronized thalamo-cortical visual-like input. We found that attacking layer 5 hub neurons is most harmful to the structural and functional integrity of the NMC. The significance of our results for understanding the role of specific neuron types and cortical layers for disease manifestation is discussed.

Linking hubness, embryonic neurogenesis, transcriptomics and diseases in human brain networks

“…Within the neocortex, where different neuronal populations are generated at sequential neurogenic stages 33 , but where these birth-dated circuits cannot be tracked by MRI, hubs are related to neurogenesis. A recent computational study of neocortical circuits reported that targeted-injuries on the layer-five hub-neurons was producing the greatest damage to the structural functional integrity of neocortical circuits 34 . Layer 5 neurons are amongst the earliest generated in the neocortex.…”

Parallel reconstruction of the excitatory and inhibitory inputs received by single neurons reveals the synaptic basis of recurrent spiking

“…Finally, we investigated the circuit architecture that supported the observed spiking regime. Highly connected hub neurons are believed to be important for the coordination of network activity (Bonifazi et al 2009; Cossart 2014; Gal et al 2021), but electrophysiological characterizations of their connections are scarce. Here, we also identified a minority of cells with high connection outdegrees.…”

Gestational immune activation disrupts hypothalamic neurocircuits of maternal care behavior

“…However, not all Gal + neurons expressed tlr3 , Ifnar1, and Ifnar2 mRNAs at the time point of sequencing of open-source data. There are a number of possibilities given this heterogeneity: (i) the expression profiles of these genes are environment-driven, or metabolism-driven and could fluctuate during pregnancy; (ii) a small subset of cells alike “hub” neurons in the hippocampus or neocortex [ 80 , 81 ] could imprint large-scale neurocircuit modifications as starter cells. Thus, a circumspect number of expression foci could be sufficient for re-entraining the mPOA; (iii) neither single-cell RNA-seq nor epigenome-related sequencing data exist on glial cells of the mPOA, or more broadly the brain.…”