Emergence of local and global synaptic organization on cortical dendrites

Abstract

Synaptic inputs on cortical dendrites are organized with remarkable subcellular precision at the micron level. This organization emerges during early postnatal development through patterned spontaneous activity and manifests both locally where nearby synapses are significantly correlated, and globally with distance to the soma. We propose a biophysically motivated synaptic plasticity model to dissect the mechanistic origins of this organization during development and elucidate synaptic clustering of different stimulus features in the adult. Our model captures local clustering of orientation in ferret and receptive field overlap in mouse visual cortex based on the receptive field diameter and the cortical magnification of visual space. Including action potential back-propagation explains branch clustering heterogeneity in the ferret and produces a global retinotopy gradient from soma to dendrite in the mouse. Therefore, by combining activity-dependent synaptic competition and species-specific receptive fields, our framework explains different aspects of synaptic organization regarding stimulus features and spatial scales.

Heterosynaptic Plasticity and the Experience-Dependent Refinement of Developing Neuronal Circuits

“…Several modeling studies have made predictions on the mechanisms that underlie the formation of functional clusters (Legenstein and Maass, 2011 ; Limbacher and Legenstein, 2020 ). Kirchner and Gjorgjieva ( 2021 ) successfully recapitulated previous experimental findings on the functional clustering of excitatory synapses in visual cortical areas by using a heterosynaptic plasticity model based on activity-dependent interactions between BDNF and proBDNF (Winnubst et al, 2015 ). The authors found that this introduced a distance-dependent and timing-dependent competition between synapses.…”

“…Due to these differences, we have some insight into the prerequisites for functional clustering. For example, the presence of cortical columns or topographic maps, in which there exists a spatial organization of neurons with similar response properties, can explain differences in functional clustering between species (Kirchner and Gjorgjieva, 2021 ). In V1, neurons demonstrate functional clustering for orientation preference specifically in species that have orientation columns and small receptive field diameters for visual space, such as macaques and ferrets (Wilson et al, 2016 ; Ju et al, 2020 ; Scholl et al, 2021 ).…”

Local dendritic balance enables learning of efficient representations in networks of spiking neurons

“…We argue that these two disparities can be resolved, if the individual continuous inputs provided to our model are seen as the resulting currents of clustered, correlated synapses. How this clustering could be organized by synaptic plasticity is a matter of ongoing research ( 68 ), and it will have to be the subject of future work to reconcile these plasticity mechanisms with representation learning.…”

Emergence of synaptic organization and computation in dendrites

“…There is accumulating evidence that a substantial amount of the dendritic organization across these scales emerges already during early development ( ; ; ; ; ; ). This early emergence is particularly noteworthy as neural activity during these early phases primarily arises spontaneously ( ), raising the question of how the brain can precisely arrange synaptic inputs across scales without sensory input.…”

“…Specific activity-dependent plasticity mechanisms drive this connectivity refinement ( ). The exact form of these plasticity mechanisms and their functional implications are an active area of research ( ; ; ; ; ).…”