Convergence and function of distinct corticocortical and transthalamic synapses across sensory processing hierarchies
- 1University at Buffalo
Abstract
Communication among cortical regions underlies fundamental functions of the brain. Thus, it is essential to understand the synaptic mechanisms by which distinct cortical regions become functionally connected. While direct corticocortical synaptic connections between cortical regions have traditionally been considered the primary mode of cortex- wide interaction, these regions can also interact indirectly through transthalamic pathways that engage higher-order regions of the thalamus. Yet, the mechanisms by which these two distinct inter-cortical synaptic pathways exert their influence on their target cortical neurons are largely unknown. A major obstacle to the targeted synaptic analysis of these pathways has been the lack of an appropriate method to genetically label them, especially in the same preparation. Here, using a combination of viral vector methods for anterograde transsynaptic and retrograde labeling along with optogenetic activation of long-range synaptic terminals in ex vivo slices of mouse visual cortical areas, we uncover a number of previously unknown features of corticocortical pathways and their transthalamic counterparts. First, corticocortical and transthalamic pathways originating from the same cortical source are largely monosynaptically integrated by target cortical neurons, though with an integration frequency that depends on the hierarchical level of the sensory processing stream. Second, feedforward transthalamic and corticocortical synapses are dynamically distinct and activate responses with distinct postsynaptic receptor composition, whereas these same pathways in the feedback direction elicit synaptic responses that are largely comparable. Overall, these results provide a novel synaptic-level framework for understanding how cortical and thalamic axon pathways shape the flow of information across interareal cortical networks.
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BibTeX
@misc{haller2026convergence,
title = {{Convergence and function of distinct corticocortical and transthalamic synapses across sensory processing hierarchies}},
author = {M. Haller and G. T. Neske},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.08.750213},
url = {https://www.biorxiv.org/content/10.64898/2026.09.08.750213v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Convergence and function of distinct corticocortical and transthalamic synapses across sensory processing hierarchies
AU - M. Haller
AU - G. T. Neske
PY - 2026
DA - 2026/09/08
PB - bioRxiv
DO - 10.64898/2026.09.08.750213
UR - https://www.biorxiv.org/content/10.64898/2026.09.08.750213v1
AB - Communication among cortical regions underlies fundamental functions of the brain. Thus, it is essential to understand the synaptic mechanisms by which distinct cortical regions become functionally connected. While direct corticocortical synaptic connections between cortical regions have traditionally been considered the primary mode of cortex- wide interaction, these regions can also interact indirectly through transthalamic pathways that engage higher-order regions of the thalamus. Yet, the mechanisms by which these two distinct inter-cortical synaptic pathways exert their influence on their target cortical neurons are largely unknown. A major obstacle to the targeted synaptic analysis of these pathways has been the lack of an appropriate method to genetically label them, especially in the same preparation. Here, using a combination of viral vector methods for anterograde transsynaptic and retrograde labeling along with optogenetic activation of long-range synaptic terminals in ex vivo slices of mouse visual cortical areas, we uncover a number of previously unknown features of corticocortical pathways and their transthalamic counterparts. First, corticocortical and transthalamic pathways originating from the same cortical source are largely monosynaptically integrated by target cortical neurons, though with an integration frequency that depends on the hierarchical level of the sensory processing stream. Second, feedforward transthalamic and corticocortical synapses are dynamically distinct and activate responses with distinct postsynaptic receptor composition, whereas these same pathways in the feedback direction elicit synaptic responses that are largely comparable. Overall, these results provide a novel synaptic-level framework for understanding how cortical and thalamic axon pathways shape the flow of information across interareal cortical networks.
ER -