The dendrites of neocortical pyramidal neurons are excitable. However, it is unknown how synaptic inputs engage nonlinear dendritic mechanisms during sensory processing in vivo, and how they in turn influence action potential output. Here, we provide a quantitative account of the relationship between synaptic inputs, nonlinear dendritic events, and action potential output. We developed a detailed pyramidal neuron model constrained by in vivo dendritic recordings. We drive this model with realistic input patterns constrained by sensory responses measured in vivo and connectivity measured in vitro. We show mechanistically that under realistic conditions, dendritic Na and NMDA spikes are the major determinants of neuronal output in vivo. We demonstrate that these dendritic spikes can be triggered by a surprisingly small number of strong synaptic inputs, in some cases even by single synapses. We predict that dendritic excitability allows the 1% strongest synaptic inputs of a neuron to control the tuning of its output. Active dendrites therefore allow smaller subcircuits consisting of only a few strongly connected neurons to achieve selectivity for specific sensory features.
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http://dx.doi.org/10.1073/pnas.2017339118 | DOI Listing |
Nat Neurosci
January 2025
Brain Research Institute, University of Zurich, Zurich, Switzerland.
Appropriate risk evaluation is essential for survival in complex, uncertain environments. Confronted with choosing between certain (safe) and uncertain (risky) options, animals show strong preference for either option consistently across extended time periods. How such risk preference is encoded in the brain remains elusive.
View Article and Find Full Text PDFJ Neurosci
January 2025
Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA, 27599.
Blunted sensitivity to ethanol's aversive effects can increase motivation to consume ethanol; yet, the neurobiological circuits responsible for encoding these aversive properties are not fully understood. Plasticity in cells projecting from the anterior insular cortex (aIC) to the basolateral amygdala (BLA) is critical for taste aversion learning and retrieval, suggesting this circuit's potential involvement in modulating the aversive properties of ethanol. Here, we tested the hypothesis that GABAergic currents onto aIC-BLA projections would be facilitated as a consequence of retrieval of an ethanol-conditioned taste aversion (CTA).
View Article and Find Full Text PDFBrain Struct Funct
January 2025
Department of Physiology and Neurobiology, Laboratory of Molecular and Systems Neurobiology, Eötvös Loránd University, Budapest, Hungary.
The lateral septum (LS) demonstrates activation in response to pup exposure in mothers, and its lesions eliminate maternal behaviors suggesting it is part of the maternal brain circuitry. This study shows that the density of pup-activated neurons in the ventral subdivision of the LS (LSv) is nearly equivalent to that in the medial preoptic area (MPOA), the major regulatory site of maternal behavior in rat dams. However, when somatosensory inputs including suckling were not allowed, pup-activation was markedly reduced in the LSv.
View Article and Find Full Text PDFHumans exhibit unique cognitive abilities within the animal kingdom, but the neural mechanisms driving these advanced capabilities remain poorly understood. Human cortical neurons differ from those of other species, such as rodents, in both their morphological and physiological characteristics. Could the distinct properties of human cortical neurons help explain the superior cognitive capabilities of humans? Understanding this relationship requires a metric to quantify how neuronal properties contribute to the functional complexity of single neurons, yet no such standardized measure currently exists.
View Article and Find Full Text PDFNat Neurosci
January 2025
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, UK.
Brain-resident macrophages, microglia, have been proposed to have an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that several neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse that lacks microglia (Csf1r), we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated.
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