Aging disrupts the link between network centrality and functional properties of prefrontal neurons during memory-guided behavior

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 16, 2025

The prefrontal cortex (PFC) is vital for higher cognitive functions and displays neuronal heterogeneity, with activity varying significantly across individual neurons. Using calcium imaging in the medial PFC (mPFC) of mice, we investigate whether differences degree centrality-a measure connectivity strength within local circuits-could explain this diversity its functional implications. In young adults, neurons high centrality, inferred from resting-state activity, exhibit reliable stable action-plan selectivity during memory-guided tasks, suggesting that closely linked to heterogeneity. This relationship, however, deteriorates middle-aged older mice. A computational model simulating age-related declines synaptic plasticity reproduces these results. centrality also predicts cross-modal selectivity, but predictive power diminishes age. Furthermore, are spatially clustered, a pattern fades aging. These findings reveal significant aging impact on network properties parallel spatial organization mPFC.

Language: Английский

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Disinhibition by VIP interneurons is orthogonal to cross-modal attentional modulation in primary visual cortex

Neuron, Journal Year: 2023, Volume and Issue: 112(4), P. 628 - 645.e7

Published: Dec. 8, 2023

Attentional modulation of sensory processing is a key feature cognition; however, its neural circuit basis poorly understood. A candidate mechanism the disinhibition pyramidal cells through vasoactive intestinal peptide (VIP) and somatostatin (SOM)-positive interneurons. However, interaction attentional VIP-SOM has never been directly tested. We used all-optical methods to bi-directionally manipulate VIP interneuron activity as mice performed cross-modal attention-switching task. measured activities VIP, SOM, parvalbumin (PV)-positive interneurons neurons identified in same tissue found that although all cell classes was modulated by both attention manipulation, their effects were orthogonal. Attention relied on distinct patterns changes reorganization interactions between inhibitory excitatory cells. Circuit modeling revealed precise network architecture consistent with multiplexing strong yet non-interacting modulations population.

Language: Английский

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Cell type-specific connectome predicts distributed working memory activity in the mouse brain

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 4, 2024

Recent advances in connectomics and neurophysiology make it possible to probe whole-brain mechanisms of cognition behavior. We developed a large-scale model the multiregional mouse brain for cardinal cognitive function called working memory, brain’s ability internally hold process information without sensory input. The is built on mesoscopic connectome data interareal cortical connections endowed with macroscopic gradient measured parvalbumin-expressing interneuron density. found that memory coding distributed yet exhibits modularity; spatial pattern mnemonic representation determined by long-range cell type-specific targeting density classes. Cell graph measures predict activity patterns core subnetwork maintenance. shows numerous attractor states, which are self-sustained internal states (each engaging distinct subset areas). This work provides framework interpret recordings during cognition, while highlighting need connectomics.

Language: Английский

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Distributed representations of prediction error signals across the cortical hierarchy are synergistic

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 10, 2024

Abstract A relevant question concerning inter-areal communication in the cortex is whether these interactions are synergistic. Synergy refers to complementary effect of multiple brain signals conveying more information than sum each isolated signal. Redundancy, on other hand, common shared between signals. Here, we dissociated cortical encoding (synergy) from those sharing (redundancy) during prediction error (PE) processing. We analyzed auditory and frontal electrocorticography (ECoG) five awake marmosets performing two distinct oddball tasks investigated what extent event-related potentials (ERP) broadband (BB) dynamics encoded synergistic redundant about PE The conveyed by ERPs BB was even at lower stages hierarchy regions. Using a brain-constrained neural network, simulated synergy redundancy observed experimental results demonstrated that emergence regions requires presence strong, long-distance, feedback, feedforward connections. These indicate distributed representations across can be highly

Language: Английский

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Independent response modulation of visual cortical neurons by attentional and behavioral states

Neuron, Journal Year: 2022, Volume and Issue: 110(23), P. 3907 - 3918.e6

Published: Sept. 21, 2022

Sensory processing is influenced by cognitive and behavioral states, but how these states interact to modulate responses of individual neurons unknown. We trained mice in a visual discrimination task wherein they attended different locations within hemifield while running or sitting still, enabling us examine are modulated spatial attention behavior. found that improved performance strengthened excitatory the primary cortex whose receptive fields overlapped with location. Although were both running, magnitudes influences not correlated. While running-dependent modulation was stable across days, attentional dynamic, influencing degrees after repeated changes states. Thus, despite similar effects on neural responses, act independently dynamics, implying separable mechanisms for their implementation.

Language: Английский

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Functional alterations of the prefrontal circuit underlying cognitive aging in mice

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 9, 2023

Executive function is susceptible to aging. How aging impacts the circuit-level computations underlying executive remains unclear. Using calcium imaging and optogenetic manipulation during memory-guided behavior, we show that working-memory coding relevant recurrent connectivity in mouse medial prefrontal cortex (mPFC) are altered as early middle age. Population activity young adult mPFC exhibits dissociable yet overlapping patterns between tactile auditory modalities, enabling crossmodal memory concurrent with modality-dependent coding. In age, however, remarkably diminishes while persists, both types of decay advanced Resting-state functional connectivity, especially among memory-coding neurons, decreases already suggesting deteriorated circuits for maintenance. Optogenetic inactivation reveals middle-aged heightened vulnerability perturbations. These findings elucidate alterations circuit unfold age deteriorate further a hallmark cognitive

Language: Английский

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Dynamics of spiral wave chimeras subjected to a local feedback control

Communications in Nonlinear Science and Numerical Simulation, Journal Year: 2025, Volume and Issue: unknown, P. 108859 - 108859

Published: April 1, 2025

Language: Английский

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The Computational Bottleneck of Basal Ganglia Output (and What to Do About it)

eNeuro, Journal Year: 2025, Volume and Issue: 12(4), P. ENEURO.0431 - 23.2024

Published: April 1, 2025

What the basal ganglia do is an oft-asked question; answers range from selection of actions to specification movement estimation time. Here, I argue that how what they a less-asked but equally important question. show output regions create stringent computational bottleneck, both structurally, because have far fewer neurons than their target regions, and dynamically, tonic, inhibitory output. My proposed solution this bottleneck activity neuron setting weight basis function, function defined by neuron’s synaptic contacts. illustrate may work in practice, allowing shift cortical dynamics control eye movements via superior colliculus. This can account for troubling issues our understanding ganglia: why we see increasing during behavior, rather only decreasing as predicted theories based on disinhibition, seems so many codes squashed into such tiny region brain.

Language: Английский

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The entire brain, more or less, is at work: ‘Language regions’ are artefacts of averaging

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 3, 2023

Abstract Models of the neurobiology language suggest that a small number anatomically fixed brain regions are responsible for functioning. This observation derives from centuries examining injury causing aphasia and is supported by decades neuroimaging studies. The latter rely on thresholded measures central tendency applied to activity patterns resulting heterogeneous stimuli. We hypothesised these methods obscure whole distribution supporting language. Specifically, cortical ‘language regions’ corresponding network’ consist input connectivity hubs. primarily coordinate peripheral whose variable, making them likely be averaged out following thresholding. tested hypotheses in two studies using meta-analyses functional magnetic resonance imaging during film watching. Both converged averaging over words localised historically associated with but distributed throughout most when not sensorimotor properties those words. word composed highly data shows hubs fixed. Rather, they spatiotemporally dynamic, connections 44% at any moment, only appear aggregate time. Results an artefact indiscriminately across representations linguistic processes. mostly dynamic coordinating whole-brain distributions networks processing complexities real-world use, explaining why damage results aphasia.

Language: Английский

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Emergence of distributed working memory in a human brain network model

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 27, 2023

Abstract Working memory is a fundamental cognitive function which allows to transiently store and manipulate relevant information in memory. While it has been traditionally linked activity specific prefrontal cortical areas, recent electrophysiological imaging evidence shown co-occurrent activities different brain regions during working To dissect the mechanisms behind emergence of such distributed human brain, we built analyzed detailed, data-constrained model combining multiple sources large-scale data. The reveals patterns rely on long-range synaptic projections, differing from classical models where emerges due local recurrent connectivity. When compared existing regarding areas memory, our explains almost 80% observed variability across areas. Our results predict important differences between non-human primates, propose potential solution for debate role early visual encoding. This work provides novel approach simulate combines richness dynamics with insight mechanistic functions.

Language: Английский

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