The responses of neurons in sensory cortex depend on the summation of excitatory and inhibitory synaptic inputs. How the excitatory and inhibitory inputs scale with stimulus depends on the network architecture, which ranges from the lateral inhibitory configuration where excitatory inputs are more narrowly tuned than inhibitory inputs, to the co-tuned configuration where both are tuned equally. The underlying circuitry that gives rise to lateral inhibition and co-tuning is yet unclear. Using large-scale network simulations with experimentally determined connectivity patterns and simulations with rate models, we show that the spatial extent of the input determined the configuration: there was a smooth transition from lateral inhibition with narrow input to co-tuning with broad input. The transition from lateral inhibition to co-tuning was accompanied by shifts in overall gain (reduced), output firing pattern (from tonic to phasic) and rate-level functions (from non-monotonic to monotonically increasing). The results suggest that a single cortical network architecture could account for the extended range of experimentally observed response types between the extremes of lateral inhibitory versus co-tuned configurations.
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http://dx.doi.org/10.1371/journal.pcbi.1002161 | DOI Listing |
Exp Hematol Oncol
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Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
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January 2025
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address:
Amyotrophic lateral sclerosis (ALS) presents a substantial challenge due to its complex nature, limited effective treatment options, and modest benefits from current therapies in slowing disease progression. This study explores the potential of intranasal (IN) delivery to enhance the CNS delivery of riluzole (RLZ), a standard ALS treatment which is subject to blood-brain barrier efflux mechanisms. Additionally, the impact of elacridar (ELC), an efflux pump inhibitor, on IN RLZ CNS bioavailability was examined.
View Article and Find Full Text PDFPlant Commun
January 2025
Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea. Electronic address:
Roots absorb water and nutrients from the soil, support the plant's aboveground organs, and detect environmental changes, making them crucial targets for improving crop productivity. Roots are particularly sensitive to soil salinity, a major abiotic stress that poses a serious threat to global agriculture. In response to salt stress, plants suppress root meristem size, thus reducing root growth; however, the mechanisms underlying this growth restriction remain unclear.
View Article and Find Full Text PDFEur J Neurol
January 2025
Department of Pharmacotherapy, University of Utah Health, Salt Lake City, Utah, USA.
Background: Reduction of intracellular Na accumulation through late Na current inhibition has been recognized as a target for cardiac Ca handling which underlies myocardial contractility and relaxation in heart failure (HF). Riluzole, an Na channel blocker with enhancement of Ca-activated K channel function, used for management of amyotrophic lateral sclerosis (ALS), is effective in suppressing Ca leak and therefore may improve cardiac function.
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