Biology subjects

Kirchner, J. H.

Publications and source records attributed to Kirchner, J. H..

4 recordsLinked to original sources

bioRxiv2024

Correlated spontaneous activity sets up multi-sensory integration in the developing higher-order cortex

To perceive and navigate complex sensory environments, animals combine sensory information from multiple modalities in specialized brain circuits. Known as multisensory integration, this process typically depends on the existence of co-aligned topographic connections from several sensory areas to downstream circuits exhibiting multimodal representations. How such topographically co-aligned connectivity necessary for multisensory integration gets set up in early stages of development is still unknown. Inspired by the role of spontaneous activity in refining topographic connectivity between early sensory circuits, here we investigated the potential of such spontaneous activity to also guide the co-alignment of multiple sensory modalities in RL, a higher-order associative cortical area rostro-lateral to V1. Analyzing spontaneous activity simultaneously recorded in primary visual and somatosensory cortex and area RL at different developmental ages before sensory experience, we identify candidate features of this activity to guide the emergence of co-aligned topographic multisensory projections with somatosensory leading the visual projection. We confirm this hypothesis using a computational model of activity-dependent circuit refinement, and show that the correlation of spontaneous activity between the visual and somatosensory primary cortex can establish an optimal fraction of multisensory neurons in RL for stimulus decoding. Our model provides an exciting new computational perspective of the role of spontaneous activity in the emergence of topographically co-aligned multimodal sensory representations in downstream circuits, specialized for the processing of rich sensory environments.

neuroscience↗

bioRxiv2022

A local activity-dependent learning rule shapes dendritic morphologies and synaptic organization

Dendritic branching and synaptic organization shape single-neuron and network computations. How they emerge simultaneously during brain development as neurons become integrated into functional networks is still not mechanistically understood. Here, we propose a mechanistic model in which dendrite growth and the organization of synapses arise from the interaction of activity-independent cues from potential synaptic partners and local activity-dependent synaptic plasticity. Consistent with experiments, three phases of dendritic growth - overshoot, pruning, and stabilization - emerge naturally in the model. The model generates stellate-like dendritic morphologies that capture several morphological features of biological neurons under normal and perturbed learning rules, reflecting biological variability. Model-generated dendrites have approximately optimal wiring length consistent with experimental measurements. In addition to establishing dendritic morphologies, activity-dependent plasticity rules organize synapses into spatial clusters according to the correlated activity they experience. We demonstrate that a trade-off between activity-dependent and -independent factors influences dendritic growth and synaptic location throughout development, suggesting that early developmental variability can affect mature morphology and synaptic function. Therefore, a single mechanistic model can capture dendritic growth and account for the synaptic organization of correlated inputs during development. Our work suggests concrete mechanistic components underlying the emergence of dendritic morphologies and synaptic formation and removal in function and dysfunction, and provides experimentally testable predictions for the role of individual components.

neuroscience↗

bioRxiv2020

Adaptation of spontaneous activity in the developing visual cortex

Spontaneous activity drives the establishment of appropriate connectivity in different circuits during brain development. In the mouse primary visual cortex, two distinct patterns of spontaneous activity occur before vision onset: local low-synchronicity events originating in the retina, and global high-synchronicity events originating in the cortex. We sought to determine the contribution of these activity patterns to jointly organize network connectivity through different activity-dependent plasticity rules. We found that local events shape cortical input selectivity and topography, while global events have a homeostatic role regulating connection strength. To generate robust selectivity, we predicted that global events should adapt their amplitude to the history of preceding cortical activation, and confirmed by analyzing in vivo spontaneous cortical activity. This adaptation led to the sparsification of spontaneous activity on a slower timescale during development, demonstrating the remarkable capacity of the developing sensory cortex to acquire sensitivity to visual inputs after eye-opening.

neuroscience↗

bioRxiv2019

A unifying framework for synaptic organization on cortical dendrites

Dendritic synaptic inputs are organized into functional clusters 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 vs. receptive field overlap in mouse visual cortex based on the cortical magnification of visual space. Including a back-propagating action potential explains branch clustering heterogeneity in the ferret, and produces a global retinotopy gradient from soma to dendrite in the mouse. Therefore, our framework suggests that sub-cellular precision in connectivity can already be established in development, and unifies different aspects of synaptic organization across species and scales.

neuroscience↗