Information processing and coding were analysed in dissociated hippocampal cultures, grown on multielectrode arrays. Multisite stimulation was used to activate different neurons and pathways of the network. The neural activity was binned into firing rates and the variability of the firing of individual neurons and of the whole population was analysed. In individual neurons, the timing of the first action potential (AP) was rather precise from trial to trial, whereas the timing of later APs was much more variable. Pooling APs in an ensemble of neurons reduced the variability of the response and allowed stimuli varying in intensity to be distinguished reliably in a single trial. A similar decrease of variability was observed pooling the first evoked APs in an ensemble of neurons. The size of the neuronal pool (approximately 50-100 neurons) and the time bin (approximately 20 ms) necessary to provide reproducible responses are remarkably similar to those obtained in in vivo preparations and in small nervous systems. Blockage of excitatory synaptic pathways mediated by NMDA receptors improved the mutual information between the evoked response and stimulus properties. When inhibitory GABAergic pathways were blocked by bicuculline the opposite effect was obtained. These results show how ensemble averages and an appropriate balance between inhibition and excitation allow neuronal networks to process information in a fast and reliable way.
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http://dx.doi.org/10.1111/j.1460-9568.2005.04464.x | DOI Listing |
Alzheimers Res Ther
January 2025
Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.
Background: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.
Methods: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1, PSEN2, and APP and mechanistically characterized by integrating RNA-seq and ATAC-seq.
Sci Rep
January 2025
Department of Neurology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave, Chicago, IL, 60611, USA.
Corticospinal motor neurons (CSMN), located in the motor cortex of the brain, are one of the key components of the motor neuron circuitry. They are in part responsible for the initiation and modulation of voluntary movement, and their degeneration is the hallmark for numerous diseases, such as amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia, and primary lateral sclerosis. Cortical hyperexcitation followed by in-excitability suggests the early involvement of cortical dysfunction in ALS pathology.
View Article and Find Full Text PDFAm J Hum Genet
December 2024
Laboratory of Human Genetics & Therapeutics, Genome Institute of Singapore (GIS), A(∗)STAR, Singapore, Singapore; Laboratory of Human Genetics & Therapeutics, BESE, KAUST, Thuwal, Saudi Arabia; Department of Physiology, Cardiovascular Disease Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address:
Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.
View Article and Find Full Text PDFNat Commun
January 2025
School of Applied and Engineering Physics, Cornell University, Ithaca, NY, USA.
Energy efficiency in computation is ultimately limited by noise, with quantum limits setting the fundamental noise floor. Analog physical neural networks hold promise for improved energy efficiency compared to digital electronic neural networks. However, they are typically operated in a relatively high-power regime so that the signal-to-noise ratio (SNR) is large (>10), and the noise can be treated as a perturbation.
View Article and Find Full Text PDFJ Neurosci
January 2025
Nervous System Disorders and Therapy, GIGA Institute, University of Liège, 4000 Liège, Belgium
Synaptic vesicle glycoprotein 2A (SV2A) is a presynaptic protein targeted by the antiseizure drug levetiracetam. One or more of the three SV2 genes is expressed in all neurons and is essential to normal neurotransmission. Loss of SV2A results in a seizure phenotype in mice and mutations in humans are also linked to congential seizures.
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