Search bioRxivSearch

bioRxiv · 10.1101/702936

Posterior hippocampal spindle-ripples co-occur with neocortical theta-bursts and down-upstates, and phase-lock with parietal spindles during NREM sleep in humans

Abstract

Human anterior and posterior hippocampus (aHC, pHC) differ in connectivity and behavioral correlates. Here we report physiological differences. During NREM sleep, the human hippocampus generates sharpwave-ripples (SWR) similar to those which in rodents mark memory replay. We show that while pHC generates SWR, it also generates about as many spindle-ripples (SSR: ripples phase-locked to local spindles). In contrast, SSR are rare in aHC. Like SWR, SSR often co-occur with neocortical theta bursts (TB), downstates (DS), spindles (SS) and upstates (US), which coordinate cortico-hippocampal interactions and facilitate consolidation in rodents. SWR co-occur with these waves in widespread cortical areas, especially fronto-central. These waves typically occur in the sequence TB-DS-SS-US, with SWR usually occurring prior to SS-US. In contrast, SSR occur [~]350 ms later, with a strong preference for co-occurrence with posterior-parietal SS. pHC-SS were strongly phase-locked with parietal-SS, and pHC-SSR were phase-coupled with pHC-SS and parietal-SS. Human SWR (and associated replay events, if any) are separated by [~]5 s on average, whereas ripples on successive SSR peaks are separated by only [~]80 ms. These distinctive physiological properties of pHC-SSR enable an alternative mechanism for hippocampal engagement with neocortex.\n\nSignificance StatementRodent hippocampal neurons replay waking events during sharpwave-ripples in NREM sleep, facilitating memory transfer to a permanent cortical store. We show that human anterior hippocampus also produces sharpwave-ripples, but spindle-ripples predominate in posterior. Whereas sharpwave-ripples typically occur as cortex emerges from inactivity, spindle-ripples typically occur at peak cortical activity. Furthermore, posterior hippocampal spindle-ripples are tightly coupled to posterior parietal locations activated by conscious recollection. Finally, multiple spindle-ripples can recur within a second, whereas sharpwave-ripples are separated by about 5s. The human posterior hippocampus is considered homologous to rodent dorsal hippocampus, which is thought to be specialized for consolidation of specific memory details. We speculate that these distinct physiological characteristics of posterior hippocampal spindle-ripples may support a related function in humans.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Jiang, X., Gonzalez-Martinez, J., Halgren, E.. 2019-07-15. Posterior hippocampal spindle-ripples co-occur with neocortical theta-bursts and down-upstates, and phase-lock with parietal spindles during NREM sleep in humans. https://doi.org/10.1101/702936

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

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience