Recent experiments have revealed fine structure in cortical microcircuitry. In particular, bidirectional connections are more prevalent than expected by chance. Whether this fine structure affects cortical dynamics and function has not yet been studied. Here we investigate the effects of excess bidirectionality in a strongly recurrent network model of rodent V1. We show that reciprocal connections have only a very weak effect on orientation selectivity. We find that excess reciprocity between inhibitory neurons slows down the dynamics and strongly increases the Fano factor, while for reciprocal connections between excitatory and inhibitory neurons it has the opposite effect. In contrast, excess bidirectionality within the excitatory population has a minor effect on the neuronal dynamics. These results can be explained by an effective delayed neuronal self-coupling which stems from the fine structure. Our work suggests that excess bidirectionality between inhibitory neurons decreases the efficiency of feature encoding in cortex by reducing the signal to noise ratio. On the other hand it implies that the experimentally observed strong reciprocity between excitatory and inhibitory neurons improves the feature encoding.
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http://dx.doi.org/10.1038/s41598-019-40183-8 | DOI Listing |
Theranostics
January 2025
Department of Critical Care Medicine and Department of Anaesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China, 710032.
Record-breaking heatwaves caused by greenhouse effects lead to multiple hyperthermia disorders, the most serious of which is exertional heat stroke (EHS) with the mortality reaching 60 %. Repeat exercise with heat exposure, termed heat acclimation (HA), protects against EHS by fine-tuning feedback control of body temperature (Tb), the mechanism of which is opaque. This study aimed to explore the molecular and neural circuit mechanisms of the HA training against EHS.
View Article and Find Full Text PDFNat Chem Biol
January 2025
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Voltage-gated ion channels (VGICs) are crucial targets for neuropsychiatric therapeutics owing to their role in controlling neuronal excitability and the established link between their dysfunction and neurological diseases, highlighting the importance of identifying modulators with distinct mechanisms. Here we report two small-molecule modulators with the same chemical scaffold, Ebio2 and Ebio3, targeting a potassium channel KCNQ2, with opposite effects: Ebio2 acts as a potent activator, whereas Ebio3 serves as a potent and selective inhibitor. Guided by cryogenic electron microscopy, patch-clamp recordings and molecular dynamics simulations, we reveal that Ebio3 attaches to the outside of the inner gate, employing a unique non-blocking inhibitory mechanism that directly squeezes the S6 pore helix to inactivate the KCNQ2 channel.
View Article and Find Full Text PDFCommun Med (Lond)
January 2025
Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Background: Alzheimer's disease (AD) is a serious neurodegenerative disorder without a clear understanding of pathophysiology. Recent experimental data have suggested neuronal excitation-inhibition (E-I) imbalance as an essential element of AD pathology, but E-I imbalance has not been systematically mapped out for either local or large-scale neuronal circuits in AD, precluding precise targeting of E-I imbalance in AD treatment.
Method: In this work, we apply a Multiscale Neural Model Inversion (MNMI) framework to the resting-state functional MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to identify brain regions with disrupted E-I balance in a large network during AD progression.
In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory, inhibitory, and medium spiny neurons and the involvement of amygdala neurons in both mouse and human single-cell analyses.
View Article and Find Full Text PDFJ Neurophysiol
January 2025
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
Anatomical studies have revealed a prominent role for feedback projections in the primate visual cortex. Theoretical models suggest that these projections support important brain functions, like attention, prediction, and learning. However, these models make different predictions about the relationship between feedback connectivity and neuronal stimulus selectivity.
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