The Impact of Neuron Morphology on Cortical Network Architecture

Abstract

Developmental programs that guide neurons and their neurites into specific subvolumes of the mammalian neocortex give rise to lifelong constraints for the formation of synaptic connections. To what degree do these constraints affect cortical wiring diagrams? Here we introduce an inverse modeling approach to show how cortical networks would appear if they were solely due to the spatial distributions of neurons and neurites. We find that neurite packing density and morphological diversity will inevitably translate into non-random pairwise and higher-order connectivity statistics. More importantly, we show that these non-random wiring properties are not arbitrary, but instead reflect the specific structural organization of the underlying neuropil. Our predictions are consistent with the empirically observed wiring specificity from subcellular to network scales. Thus, independent from learning and genetically encoded wiring rules, many of the properties that define the neocortex’ characteristic network architecture may emerge as a result of neuron and neurite development.

Functional network topography of the medial entorhinal cortex

“…This topographical pattern seems to go along with the anatomical separation from various other cell classes, visible within MEC and in between MEC and the neighboring parasubiculum. The dense anatomical packaging of grid cells may lead to elevated pairwise connectivity between them (Udvary et al, 2020), which is to be expected if grid cells are organized in continuous attractor networks (CAN) with dense, recurrent connectivity motifs (Burak and Fiete, 2009;Couey et al, 2013;Fuhs and Touretzky, 2006;McNaughton et al, 2006). Here we extend these measurements to all other spatially modulated cell classes and observe that, while trends for anatomical clustering do exist in some cell classes, namely OV and border cells, only grid cells seem to stably aggregate in groups of three or more cells.…”

“…Indeed, we observe that OV, border and HD cells appear anatomically intermingled, resembling a "salt and pepper" organization. This more homogeneous distribution, and thereby the anatomical closeness across compared to within types, might favor strong communication between cell types (Udvary et al, 2020), which may be more difficult to maintain if cells were arranged in anatomically isolated clusters instead. This might be necessary for the emergence and maintenance of firing patterns in these three cell types.…”

“…The underlying principles that dictate such patterning may derive from the constraints that speed and energy of information transfer impose on brain networks: Cell types that depend on frequent and dense information exchange may benefit from more direct anatomical proximity to each other than those that require less interaction (Luo, 2021;Song et al, 2014;Udvary et al, 2020;Wang and Clandinin, 2016). This is particularly true in brain regions in which circuit architecture might be less controlled by extrinsic factors than in many primary sensory cortices, and where the architecture instead follows more intrinsic organizational principles.…”

Mechanisms Underlying Target Selectivity for Cell Types and Subcellular Domains in Developing Neocortical Circuits

“…Similarly, a reconstruction of mouse visual cortex using electron microscopy showed that neurons with similar orientation tuning were preferentially connected even though the axons and dendrites of neurons of all orientation selectivities were intermingled (Lee et al, 2016). Although it remains possible that additional structural constraints contribute to predictable patterns of intracortical connectivity, such as the packing density of neuronal processes of different cortical cell types in sublamina within the cortex (Udvary et al, 2021), these results suggest that mechanisms beyond axodendritic overlap must contribute to preferential synapse formation among some cell types in the cortex.…”

“…These molecular signals guide growth and synaptogenesis, leading to cell-type-biased connectivity and function in adulthood. Udvary et al, 2021). Mechanisms establishing the characteristic intracortical axonal guidance and branching of different cell types remain incompletely understood but likely include extrinsic molecular cues such as semaphorin, Wnt, netrin, and ephrin family members, interactions with radial glia, selective stabilization of axon collaterals and the cellular migration patterns of inhibitory neurons (Fame et al, 2011;Leyva-Diaz and Lopez-Bendito, 2013;Hand et al, 2015;Dorskind and Kolodkin, 2021).…”