ArticleThe Journal of physiology2015
Human cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice.
Article in The Journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Modeling sources of interlaboratory variability in electrophysiological properties of mammalian neurons.Journal of neurophysiology · 2018Pooled it
- Sleep reduces CSF concentrations of beta-amyloid and tau: a randomized crossover study in healthy adults.Fluids and barriers of the CNS · 2025Trial
- Non-physiological potassium concentrations in commercial culture media trigger acute seizure-like activity in human iPSC-derived neurons.Scientific reports · 2026Article
- Characterisation of the axon initial segment and intrinsic excitability in the sub-acute phase post-ischaemic stroke.Brain communications · 2026Article
- Subarachnoid hemorrhage mediates human neocortical network, membrane potential, and action potential bursting via glutamate receptors.Communications biology · 2025Article
- Ion concentrations in CSF and serum are differentially and precisely regulated.Brain communications · 2025Article
- Morphotype-specific calcium signaling in human microglia.Journal of neuroinflammation · 2024Article
- Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations.Acta neuropathologica communications · 2023Article
- Gold nanoparticle-enhanced X-ray microtomography of the rodent reveals region-specific cerebrospinal fluid circulation in the brain.Nature communications · 2023Article
- The physiological control of eating: signals, neurons, and networks.Physiological reviews · 2022 · on this mapArticle
- Routine culture and study of adult human brain cells from neurosurgical specimens.Nature protocols · 2022Review
- Human Cerebrospinal Fluid Promotes Neuronal Circuit Maturation of Human Induced Pluripotent Stem Cell-Derived 3D Neural Aggregates.Stem cell reports · 2020Article
- Human Cerebrospinal Fluid Induces Neuronal Excitability Changes in Resected Human Neocortical and Hippocampal Brain Slices.Frontiers in neuroscience · 2020Article
- Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease.eLife · 2019Article
- Brain active transmembrane water cycling measured by MR is associated with neuronal activity.Magnetic resonance in medicine · 2019Article
- Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone.Cell metabolism · 2018Article
- Neuromodulation via the Cerebrospinal Fluid: Insights from RecentFrontiers in neural circuits · 2018Review
- Human Cerebrospinal fluid promotes long-term neuronal viability and network function in human neocortical organotypic brain slice cultures.Scientific reports · 2017Article
- Spikelets in Pyramidal Neurons: Action Potentials Initiated in the Axon Initial Segment That Do Not Activate the Soma.PLoS computational biology · 2017Article
- Neuromodulation of fast-spiking and non-fast-spiking hippocampal CA1 interneurons by human cerebrospinal fluid.The Journal of physiology · 2016Article
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
key pointsThe cerebrospinal fluid contains numerous neuromodulators at ambient levels but whether, and how, they affect the activity of central neurons is unknown. This study provides experimental evidence that human cerebrospinal fluid (hCSF) increases the excitability of hippocampal and neocortical pyramidal neurons. Hippocampal CA1 pyramidal neurons in hCSF displayed lowered firing thresholds, depolarized resting membrane potentials and reduced input resistance, mimicking properties of pyramidal neurons recorded in vivo. The excitability-increasing effect of hCSF on CA1 pyramidal neurons was entirely occluded by intracellular application of GTPγS, suggesting that neuromodulatory effects were mediated by G-protein coupled receptors. These results indicate that the CSF promotes spontaneous excitatory neuronal activity, and may help to explain observed differences in the activity of pyramidal neurons recorded in vivo and in vitro. The composition of brain extracellular fluid is shaped by a continuous exchange of substances between the cerebrospinal fluid (CSF) and interstitial fluid. The CSF is known to contain a wide range of endogenous neuromodulatory substances, but their collective influence on neuronal activity has been poorly investigated. We show here that replacing artificial CSF (aCSF), routinely used for perfusion of brain slices in vitro, with human CSF (hCSF) powerfully boosts spontaneous firing of CA1, CA3 and layer 5 pyramidal neurons in the rat brain slice. CA1 pyramidal neurons in hCSF display lowered firing thresholds, more depolarized resting membrane potentials and reduced input resistance, mimicking properties of pyramidal neurons recorded in vivo. The increased excitability of CA1 pyramidal neurons was completely occluded by intracellular application of GTPγS, suggesting that endogenous neuromodulators in hCSF act on G-protein coupled receptors to enhance excitability. We found no increase in spontaneous inhibitory synaptic transmission by hCSF, indicating a differential effect on glutamatergic and GABAergic neurons. Our findings highlight a previously unknown function of the CSF in promoting spontaneous excitatory activity, and may help to explain differences observed in the activity of pyramidal neurons recorded in vivo and in vitro.
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