bioRxiv Science⌕ Search

bioRxiv · 10.1101/2021.11.20.469406

A structured scaffold underlies activity in the hippocampus

Abstract

Place cells are believed to organize memory across space and time, inspiring the idea of the cognitive map. Yet unlike the structured activity in the associated grid and head-direction cells, they remain an enigma: their responses have been difficult to predict and are complex enough to be statistically well-described by a random process. Here we report one step toward the ultimate goal of understanding place cells well enough to predict their fields. Within a theoretical framework in which place fields are derived as a conjunction of external cues with internal grid cell inputs, we predict that even apparently random place cell responses should reflect the structure of their grid inputs and that this structure can be unmasked if probed in sufficiently large neural populations and large environments. To test the theory, we design experiments in long, locally featureless spaces to demonstrate that structured scaffolds undergird place cell responses. Our findings, together with other theoretical and experimental results, suggest that place cells build memories of external inputs by attaching them to a largely prespecified grid scaffold.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mulders, D., Yim, M. Y., Lee, J. S., Lee, A. K., Taillefumier, T., Fiete, I.. 2021-11-22. A structured scaffold underlies activity in the hippocampus. https://doi.org/10.1101/2021.11.20.469406

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

KEEP EXPLORING

Related preprints

Rab10 and Arhgef7 interact to promote axon extension by linking vesicle supply and exocytosis

The formation of functional neural circuits begins with the extension of a single axon by immature neurons. Axon elongation requires an expansion of the plasma membrane that depends on the polarization of vesicle trafficking and exocytosis. It is not completely understood how the increased transport of vesicles into the growing axon is linked to their subsequent insertion into the plasma membrane. An analysis of early stages of neuronal differentiation indicates that an asymmetry in neurite length precedes axon specification and the accumulation of PPVs in the nascent axon. We show that increasing the transport of vesicles in unpolarized neurons is sufficient to promote the extension of additional axons. This effect indicates that an increased supply of vesicles stimulates their subsequent insertion into the membrane to allow neurite growth. The link between vesicle transport and exocytosis is mediated by the interaction of Rab10 with Arhgef7. Rab10 stimulates Arhgef7 activity on PPVs as a GEF for Cdc42b to promote axon extension through exocyst-dependent exocytosis, suggesting that their interaction links the increased supply of PPVs to their exocytosis.

neuroscience↗

Subcellular Spatial Profiling Unveils Links Between Neuritic Plaques with Selective Tau Vulnerability in Alzheimer's Disease

Alzheimer's disease (AD) features widespread extracellular amyloid-{beta} plaques but selective intraneuronal tau accumulation in cortical layers II/III and V, while layer IV remains relatively resistant. Here, we combined subcellular spatial transcriptomics with co-registered A{beta} and pTau immunohistochemistry to determine why neurons exposed to comparable plaque-associated pathology differ in somatic pTau accumulation. Plaque-associated neuritic stress occurred similarly across layers, but layer IV neurons showed attenuated pTau accumulation and reduced somatic expression of a shared neurite-soma stress program involving DCTN1, CALM3, NORAD, and PIN1. Trajectory analysis within layers identified tau-vulnerable and resistant neuronal states implicating calcium signaling, retrograde transport, and lysosomal function. Notably, astrocytic APOE-neuronal LRP1 co-expression increased significantly along the pTau-vulnerable trajectory, and APOE {epsilon}4 was associated with stronger coupling of local plaque pathology to pTau-associated molecular programs. These findings reveal neuronal programs and neuron-glia interactions underlying selective tau vulnerability and resistance in AD, highlighting potential tau-targeting therapeutics.

neuroscience↗

Widespread oscillatory suppression in autism persists in the absence of psychotropic medication.

Purpose: Investigate the neural oscillatory activity associated with autism spectrum disorder (ASD) using electroencephalographic (EEG) recordings in children and adolescents. Compare the corresponding oscillatory power between ASD patients taking psychotropic medication with a drug-naive group. Methods: ASD diagnosis was done using DSM-IV and CARS (Childhood Autism Rating Scale). EEG recordings employed 22 scalp electrodes (10/20 system). ASD vs. neurotypical groups were matched for sex and age (5 females; average age: ~10 years old). We analyzed the resting state (eyes open) EEG power spectrum during ~2-minute recordings. The multitaper FFT method was used to estimate spectral power for the delta, theta, alpha, beta and gamma frequency bands. We pooled together data from several electrodes to compute comprehensive power spectra and assess the oscillatory behavior of macro brain regions. Results: We observed widespread (~4Hz - 20Hz) oscillatory suppression comprising the theta, alpha and beta frequency bands. The most widespread and robust ASD-associated power suppression was in the high theta and alpha bands. Delta and gamma bands showed no significant power change for any of the brain regions studied. Results from a subgroup of patients (N = 9) who never used psychotropics confirmed these findings, indicating that they are not an artifact of medication. Conclusion: Suppression in theta, alpha and beta oscillations may offer insights into the neurophysiological underpinnings of autism and could be used as an accessible and comprehensive tool in ASD diagnosis, regardless of the patients being or not on medication.

neuroscience↗