Scene and object information reach the entorhinal-hippocampal circuitry in partly segregated cortical processing streams. Converging evidence suggests that such information-specific streams organize the cortical - entorhinal interaction and the circuitry's inner communication along the transversal axis of hippocampal subiculum and CA1. Here, we leveraged ultra-high field functional imaging and advance Maass, Berron et al. (2015) who report two functional routes segregating the entorhinal cortex (EC) and the subiculum. We identify entorhinal subregions based on preferential functional connectivity with perirhinal Area 35 and 36, parahippocampal and retrosplenial cortical sources (referred to as ECArea35-based, ECArea36-based, ECPHC-based, ECRSC-based, respectively). Our data show specific scene processing in the functionally connected ECPHC-based and distal subiculum. Another route, that functionally connects the ECArea35-based and a newly identified ECRSC-based with the subiculum/CA1 border, however, shows no selectivity between object and scene conditions. Our results are consistent with transversal information-specific pathways in the human entorhinal-hippocampal circuitry, with anatomically organized convergence of cortical processing streams and a unique route for scene information. Our study thus further characterizes the functional organization of this circuitry and its information-specific role in memory function.
Source data that contain numerical data used to generate Figure 2, Figure 3, Figure 4, Appendix 1 Figure 2, Appendix 1 Figure 3, Appendix 1 Figure 4, Appendix 5 Figure 1 as well as group-level statistical maps (referred to as Source Code 1-16) that underlie Figure 1, Figure 2, Appendix 1 Figure 1, Appendix 1 Figure 2, Appendix 3 Figure 1, Appendix 3 Figure 2 and Appendix 4 Figure 1 have been provided under:Open Science Framework. ID 9v3qp. https://osf.io/9v3qp
Source Data from Functional Connectivity and Information Processing in the Entorhinal-Hippocampal CircuitryOpen Science Framework. ID 9v3qp.
- Emrah Düzel
- Magdalena M Sauvage
- Emrah Düzel
- David Berron
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: Informed consent and consent to publish was obtained from human participants.The study received approval by the ethics committee of Otto-von-Guericke University, Magdeburg (Germany) under reference number 128/14.
- Muireann Irish, University of Sydney, Australia
© 2022, Grande et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Chimeric RNAs have been found in both cancerous and healthy human cells. They have regulatory effects on human stem/progenitor cell differentiation, stemness maintenance, and central nervous system development. However, whether they are present in human retinal cells and their physiological functions in the retinal development remain unknown. Based on the human embryonic stem cell-derived retinal organoids (ROs) spanning from days 0 to 120, we present the expression atlas of chimeric RNAs throughout the developing ROs. We confirmed the existence of some common chimeric RNAs and also discovered many novel chimeric RNAs during retinal development. We focused on CTNNBIP1-CLSTN1 (CTCL) whose downregulation caused precocious neuronal differentiation and a marked reduction of neural progenitors in human cerebral organoids. CTCL is universally present in human retinas, ROs, and retinal cell lines, and its loss-of-function biases the progenitor cells toward retinal pigment epithelial cell fate at the expense of retinal cells. Together, this work provides a landscape of chimeric RNAs and reveals evidence for their critical role in human retinal development.
Deciphering patterns of connectivity between neurons in the brain is a critical step toward understanding brain function. Imaging-based neuroanatomical tracing identifies area-to-area or sparse neuron-to-neuron connectivity patterns, but with limited throughput. Barcode-based connectomics maps large numbers of single-neuron projections, but remains a challenge for jointly analyzing single-cell transcriptomics. Here, we established a rAAV2-retro barcode-based multiplexed tracing method that simultaneously characterizes the projectome and transcriptome at the single neuron level. We uncovered dedicated and collateral projection patterns of ventromedial prefrontal cortex (vmPFC) neurons to five downstream targets and found that projection-defined vmPFC neurons are molecularly heterogeneous. We identified transcriptional signatures of projection-specific vmPFC neurons, and verified Pou3f1 as a marker gene enriched in neurons projecting to the lateral hypothalamus, denoting a distinct subset with collateral projections to both dorsomedial striatum and lateral hypothalamus. In summary, we have developed a new multiplexed technique whose paired connectome and gene expression data can help reveal organizational principles that form neural circuits and process information.