The neuronal substrates that implement the free-energy principle and ensuing active inference at the neuron and synapse level have not been fully elucidated. This Review considers possible neuronal substrates underlying the principle. First, the foundations of the free-energy principle are introduced, and then its ability to empirically explain various brain functions and psychological and biological phenomena in terms of Bayesian inference is described. Mathematically, the dynamics of neural activity and plasticity that minimise a cost function can be cast as performing Bayesian inference that minimises variational free energy. This equivalence licenses the adoption of the free-energy principle as a universal characterisation of neural networks. Further, the neural network structure itself represents a generative model under which an agent operates. A virtue of this perspective is that it enables the formal association of neural network properties with prior beliefs that regulate inference and learning. The possible neuronal substrates that implement prior and posterior beliefs and how to empirically examine the theory are discussed. This perspective renders brain activity explainable, leading to a deeper understanding of the neuronal mechanisms underlying basic psychology and psychiatric disorders in terms of an implicit generative model.
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http://dx.doi.org/10.1016/j.neures.2021.12.003 | DOI Listing |
Nano Converg
January 2025
Bendable Electronics and Sustainable Technologies (BEST) Group, Electrical and Computer Engineering Department, Northeastern University, Boston, MA, 02115, USA.
The intriguing way the receptors in biological skin encode the tactile data has inspired the development of electronic skins (e-skin) with brain-inspired or neuromorphic computing. Starting with local (near sensor) data processing, there is an inherent mechanism in play that helps to scale down the data. This is particularly attractive when one considers the huge data produced by large number of sensors expected in a large area e-skin such as the whole-body skin of a robot.
View Article and Find Full Text PDFBrain Commun
January 2025
Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA.
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death, likely stemming from seizure activity disrupting vital brain centres controlling heart and breathing function. However, understanding of SUDEP's anatomical basis and mechanisms remains limited, hampering risk evaluation and prevention strategies. Prior studies using a neuron-specific conditional knockout mouse model of SUDEP identified the primary importance of brain-driven mechanisms contributing to sudden death and cardiorespiratory dysregulation; yet, the underlying neurocircuits have not been identified.
View Article and Find Full Text PDFJ Inherit Metab Dis
January 2025
Department of Life Sciences, Manchester Metropolitan University, Manchester, UK.
There are currently at least 70 characterised lysosomal storage diseases (LSD) resultant from inherited single-gene defects. Of these, at least 30 present with central nervous system (CNS) neurodegeneration and overlapping aetiology. Substrate accumulation and dysfunctional neuronal lysosomes are common denominator, but how variants in 30 different genes converge on this central cellular phenotype is unclear.
View Article and Find Full Text PDFJ Alzheimers Dis
January 2025
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
Background: Extracellular signal-regulated kinase 1 (ERK1) belongs to mitogen-activated protein kinases, which are essential for memory formation, cognitive function, and synaptic plasticity. During Alzheimer's disease (AD), ERK1 phosphorylates tau at 15 phosphorylation sites, leading to the formation of neurofibrillary tangles. The overactivation of ERK1 in microglia promotes the release of pro-inflammatory cytokines, which results in neuroinflammation.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
January 2025
Dept of Physiology & Cell Biology, University of Nevada Reno School of Medicine, Reno, NV. Electronic address:
Background And Aims: Gastrointestinal motility persists when peripheral cholinergic signaling is blocked genetically or pharmacologically, and a recent study suggests nitric oxide drives propagating neurogenic contractions.
Methods: To determine the neuronal substrates that underlie these contractions, we measured contractile-associated movements together with calcium responses of cholinergic or nitrergic myenteric neurons in un-paralyzed ex vivo preparations of whole mouse colon. We chose to look at these two subpopulations because they encompass nearly all myenteric neurons.
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