The Synaptic Architecture of Layer 5 Thick Tufted Excitatory Neurons in the Visual Cortex of Mice

Bodor, A. L.; Schneider-Mizell, C. M.; Zhang, C.; Elabbady, L.; Mallen, A.; Bergeson, A.; Brittain, D.; Buchanan, J.; Bumbarger, D. J.; Dalley, R.; Gamlin, C.; Joyce, E.; Kapner, D.; Kinn, S.; Mahalingam, G.; Seshamani, S.; Suckow, S.; Takeno, M.; Torres, R.; Yin, W.; Bae, J. A.; Castro, M. A.; Dorkenwald, S.; Halageri, A.; Jia, Z.; Jordan, C.; Kemnitz, N.; Lee, K.; Li, K.; Lu, R.; Macrina, T.; Mitchell, E.; Mondal, S. S.; Mu, S.; Nehoran, B.; Popovych, S.; Silversmith, W.; Turner, N. L.; Yu, S.-c.; Wong, W.; Wu, J.; Celii, B.; Campagnola, L.; Seeman, S.; Jarsky, T.; Ren, N.; Arkhipov, A.; The

doi:10.1101/2023.10.18.562531

Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.10.18.562531

The Synaptic Architecture of Layer 5 Thick Tufted Excitatory Neurons in the Visual Cortex of Mice

View original source ↗Export metadata ↓

Abstract

The neocortex is one of the most critical structures that makes us human, and it is involved in a variety of cognitive functions from perception to sensory integration and motor control. Composed of repeated modules, or microcircuits, the neocortex relies on distinct cell types as its fundamental building blocks. Despite significant progress in characterizing these cell types 1-5, an understanding of the complete synaptic partners associated with individual excitatory cell types remain elusive. Here, we investigate the connectivity of arguably the most well recognized and studied excitatory neuron in the neocortex: the thick tufted layer 5 pyramidal cell 6-10 also known as extra telencephalic (ET) 11 neurons. Although the synaptic interactions of ET neurons have been extensively explored, a comprehensive characterization of their local connectivity remains lacking. To address this knowledge gap, we leveraged a 1 mm3 electron microscopic (EM) dataset. We found that ET neurons primarily establish connections with inhibitory cells in their immediate vicinity. However, when they extend their axons to other cortical regions, they tend to connect more with excitatory cells. We also find that the inhibitory cells targeted by ET neurons are a specific group of cell types, and they preferentially inhibit ET cells. Finally, we observed that the most common excitatory targets of ET neurons are layer 5 IT neurons and layer 6 pyramidal cells, whereas synapses with other ET neurons are not as common. These findings challenge current views of the connectivity of ET neurons and suggest a circuit design that involves local competition among ET neurons and collaboration with other types of excitatory cells. Our results also highlight a specific circuit pattern where a subclass of excitatory cells forms a network with specific inhibitory cell types, offering a framework for exploring the connectivity of other types of excitatory cells.

Explore related subjects

neuroscience Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Bodor, A. L., Schneider-Mizell, C. M., Zhang, C., Elabbady, L., Mallen, A., Bergeson, A., Brittain, D., Buchanan, J., Bumbarger, D. J., Dalley, R., Gamlin, C., Joyce, E., Kapner, D., Kinn, S., Mahalingam, G., Seshamani, S., Suckow, S., Takeno, M., Torres, R., Yin, W., Bae, J. A., Castro, M. A., Dorkenwald, S., Halageri, A., Jia, Z., Jordan, C., Kemnitz, N., Lee, K., Li, K., Lu, R., Macrina, T., Mitchell, E., Mondal, S. S., Mu, S., Nehoran, B., Popovych, S., Silversmith, W., Turner, N. L., Yu, S.-c., Wong, W., Wu, J., Celii, B., Campagnola, L., Seeman, S., Jarsky, T., Ren, N., Arkhipov, A., The. 2023-10-20. The Synaptic Architecture of Layer 5 Thick Tufted Excitatory Neurons in the Visual Cortex of Mice. https://doi.org/10.1101/2023.10.18.562531

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Novel Tau Interaction Partners as Potential Biomarkers and Therapeutic Targets in Neurodegenerative Diseases

Alzheimers disease is a progressive neurodegenerative disorder leading to cognitive decline and ultimately death. One of the main hallmarks of this disease is the accumulation of pathological tau protein into neurofibrillary tangles. To better understand these pathological mechanisms, it is essential to characterize the tau protein interactome in health and disease. In this study, we performed a yeast two-hybrid screening using a human brain cDNA library, from which we identified 15 novel tau-interacting proteins that bind to full-length human tau, or its fragments: the N-terminus, microtubule-binding domain, or C-terminus. We subsequently validated these novel interactions using in vitro co-immunoprecipitation and colocalization assays with both physiological and pathological tau isoforms. Furthermore, their interactions with the human tau protein were analyzed using surface plasmon resonance. Finally, an in silico interactome analysis of these newly discovered tau-binding partners revealed several additional interactors that can link them to downstream processes critical to neurodegenerative pathways Our findings offer fresh insights into tau biology and highlight novel targets for therapeutic intervention and biomarker development.

neuroscience↗

bioRxiv2026

Early visual cortex is not functionally necessary for temporal attention: A TMS study

Temporal attention enhances the selective processing of information at a specific point in time and improves perception. Previous neuroimaging studies investigating its neural mechanisms have either conflated temporal attention with temporal expectation or provided correlational evidence. Thus, whether early visual cortex is functionally necessary for temporal attention remains unknown. Here, we combined psychophysics with transcranial magnetic stimulation (TMS) to examine whether V1/V2 are functionally necessary and play a causal role in temporal attention. Observers performed an orientation-discrimination task in which two consecutive stimuli, T1 and T2, were presented in the periphery, preceded by a precue providing either valid or neutral temporal information. Double-pulse TMS was delivered under four conditions: at T1 (T1-TMS), at T2 (T2-TMS), at both T1 and T2 (both-TMS), or not at all (none-TMS), to assess its effects on temporal attention and the efficacy of the stimulation was verified by pupil size analysis. Behavioral results revealed robust temporal attention benefits on d', reaction time, and the Balanced Integration Score (BIS) across all four TMS conditions, indicating that the benefits of temporal attention were unaffected by occipital TMS. Furthermore, pupil dilation was largest in the both-TMS condition, followed by the T1-TMS and T2-TMS conditions, and smallest in the none-TMS condition, providing physiological verification of the stimulation protocol. Together, these findings reveal the first causal evidence that the early visual cortex is not functionally necessary for endogenous temporal attention.

neuroscience↗

bioRxiv2026

Disentanglement of persistent and dynamic neural substrates of working memory

Competing theories of working memory have alternatively emphasized the importance of persistent and dynamic substrates of this cognitive function. Here, we directly tested these theories by computationally isolating the contributions of persistent and dynamic activity to working memory. We analyzed neuronal population activity recordings in macaques doing match/non-match working memory tasks. We first extracted signatures of persistent and dynamic activity through cue-specific temporal means, temporal principal components, and correlations of activity patterns across task epochs. We then generated synthetic data constrained by these signatures, and decoded cue stimuli from these data, separately from persistent and non-persistent neurons. We found that high decoding performance arose from a nuanced interplay of persistent and dynamic activity. Specifically, we could decode stimuli at empirical or above-chance levels across all tasks only from persistent neurons, but only after constraining correlations of activity patterns across epochs. In this way, we showed distinct roles for persistent and dynamic neuronal activity that help to unify two competing theories of working memory. More broadly, we also advanced computational controlled experiments as a principled framework for adjudicating between competing models of neuronal population activity.

neuroscience↗