Neuromodulation via the Cerebrospinal Fluid: Insights from Recent in Vitro Studies

The cerebrospinal fluid (CSF) occupies the brain’s ventricles and subarachnoid space and, together with the interstitial fluid (ISF), forms a continuous fluidic network that bathes all cells of the central nervous system (CNS). As such, the CSF is well positioned to actively distribute neuromodulators to neural circuits in vivo via volume transmission. Recent in vitro experimental work in brain slices and neuronal cultures has shown that human CSF indeed contains neuromodulators that strongly influence neuronal activity. Here we briefly summarize these new findings and discuss their potential relevance to neural circuits in health and disease.

• Publication year

  2018

• Venue

  Front. Neural Circuits

• Publication date

  2018-02-05

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.3389/fncir.2018.00005PMID 29459822PMCID 5807333
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Human Cerebrospinal fluid promotes long-term neuronal viability and network function in human neocortical organotypic brain slice cultures

  2017cited by this paper
• Cerebrospinal fluid levels of orexin-A and histamine, and sleep profile within the Alzheimer process.

  2017cited by this paper
• Understanding the Role of GPCR Heteroreceptor Complexes in Modulating the Brain Networks in Health and Disease

  2017cited by this paper
• Decreased allopregnanolone levels in cerebrospinal fluid obtained during status epilepticus

  2017cited by this paper
• CSF GABA is reduced in first-episode psychosis and associates to symptom severity

  2017cited by this paper
• Ancestral Circuits for the Coordinated Modulation of Brain State.

  2017cited by this paper
• Neuromodulation of fast‐spiking and non‐fast‐spiking hippocampal CA1 interneurons by human cerebrospinal fluid

  2016influential reference
• GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits.

  2016cited by this paper
• Erratum to: Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay

  2016cited by this paper
• Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

  2016cited by this paper
• The role of monoamines in modulating behavior

  2016cited by this paper
• The inner CSF–brain barrier: developmentally controlled access to the brain via intercellular junctions

  2015cited by this paper
• Revealing neuronal function through microelectrode array recordings

  2015cited by this paper
• Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay

  2015cited by this paper
• Changes in Purines Concentration in the Cerebrospinal Fluid of Pregnant Women Experiencing Pain During Active Labor

  2015cited by this paper
• Human cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice

  2015cited by this paper
• Vasopressin and oxytocin in CSF and plasma of patients with aneurysmal subarachnoid haemorrhage.

  2014cited by this paper
• Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration.

  2014cited by this paper
• Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations

  2014cited by this paper
• In vitro neuronal network activity in NMDA receptor encephalitis

  2013cited by this paper
• The θ-γ neural code.

  2013cited by this paper
• Biomarkers, mechanisms, and potential prevention of catecholamine neuron loss in Parkinson disease.

  2013cited by this paper
• Volume transmission and its different forms in the central nervous system

  2013cited by this paper
• Evolutionary Development of Neural Systems in Vertebrates and Beyond

  2013cited by this paper
• Neural associative memories and sparse coding

  2013cited by this paper
• Multielectrode array analysis of cerebrospinal fluid in Alzheimer's disease versus mild cognitive impairment: a potential diagnostic and treatment biomarker.

  2013cited by this paper
• Experimental evidence for sparse firing in the neocortex.

  2012cited by this paper
• Extrasynaptic Neurotransmission in the Modulation of Brain Function. Focus on the Striatal Neuronal–Glial Networks

  2012cited by this paper
• Neuropeptide transmission in brain circuits.

  2012cited by this paper
• Clinical significance of cerebrospinal fluid nitric oxide concentrations in degenerative cervical and lumbar diseases

  2011cited by this paper
• Intra-neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases.

  2011influential reference
• Non‐synaptic receptors and transporters involved in brain functions and targets of drug treatment

  2010cited by this paper
• The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review

  2010cited by this paper
• Cell division intersects with cell geometry.

  2010cited by this paper
• Neocortical interneurons: from diversity, strength.

  2010cited by this paper
• Sparse and powerful cortical spikes.

  2010cited by this paper
• Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy

  2010cited by this paper
• Understanding wiring and volume transmission.

  2010cited by this paper
• Galanin receptor-1 modulates 5-hydroxtryptamine-1A signaling via heterodimerization.

  2010cited by this paper
• Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

  2009cited by this paper
• Cerebrospinal fluid of brain trauma patients inhibits in vitro neuronal network function via NMDA receptors

  2009influential reference
• CSF hypocretin-1 assessment in sleep and neurological disorders.

  2008cited by this paper
• Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations

  2008cited by this paper
• The choroid plexus--cerebrospinal fluid system: undervaluated pathway of neuroendocrine signaling into the brain.

  2008influential reference
• An extremely rich repertoire of bursting patterns during the development of cortical cultures

  2006cited by this paper
• Dendritic peptide release and peptide-dependent behaviours

  2006influential reference
• Rhythms of the brain

  2006cited by this paper
• Postsynaptic depolarization requirements for LTP and LTD: a critique of spike timing-dependent plasticity

  2005cited by this paper
• Alterations in perivascular dilatory neuropeptides (CGRP, SP, VIP) in the external jugular vein and in the cerebrospinal fluid following subarachnoid haemorrhage in man

  2005cited by this paper
• Argonaute—a database for gene regulation by mammalian microRNAs

  2005cited by this paper
• XTRASYNAPTIC VOLUME TRANSMISSION AND DIFFUSION ARAMETERS OF THE EXTRACELLULAR SPACE

  2004cited by this paper
• Extrasynaptic volume transmission and diffusion parameters of the extracellular space.

  2004cited by this paper
• Sparse coding of sensory inputs.

  2004cited by this paper
• The system of cerebrospinal fluid-contacting neurons. Its supposed role in the nonsynaptic signal transmission of the brain.

  2004cited by this paper
• Peptide and peptide analog transport systems at the blood-CSF barrier.

  2004influential reference
• Dynamics of volume transmission in the brain. Focus on catecholamine and opioid peptide communication and the role of uncoupling protein 2

  2004cited by this paper
• Neurosteroids: Cerebrospinal fluid levels for Alzheimer's disease and vascular dementia diagnostics.

  2003cited by this paper
• Glutamate levels in cerebrospinal fluid in amyotrophic lateral sclerosis: a reappraisal using a new HPLC method with coulometric detection in a large cohort of patients.

  2002cited by this paper
• Treatment of Parkinson's with L-DOPA. The early discovery phase, and a comment on current problems

  2002cited by this paper
• Increase in Dopamine Turnover Occurs Early in Parkinson's Disease: Evidence from a New Modeling Approach to PET 18F-Fluorodopa Data

  2002cited by this paper
• Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.

  2001cited by this paper
• Choroid plexus: Target for polypeptides and site of their synthesis

  2001cited by this paper
• The sleep switch: hypothalamic control of sleep and wakefulness.

  2001cited by this paper
• Transmitter-Receptor Mismatches in Central Dopamine, Serotonin, and Neuropeptide Systems: Further Evidence for Volume Transmission

  2001cited by this paper
• Ultrastructural evidence for diffuse transmission by monoamine and acetylcholine neurons of the central nervous system.

  2000cited by this paper
• Facilitation of cholinergic transmission by substance P methyl ester in the mouse hippocampal slice preparation

  2000cited by this paper
• Barriers in the Immature Brain

  2000influential reference
• Differential regulation of leptin transport by the choroid plexus and blood-brain barrier and high affinity transport systems for entry into hypothalamus and across the blood-cerebrospinal fluid barrier.

  2000cited by this paper
• Neuronal synchrony: a versatile code for the definition of relations?

  1999cited by this paper
• Cerebrospinal Fluid Neuropeptides and Monoaminergic Transmitters in Patients With Trigeminal Neuralgia

  1997cited by this paper
• Muscarinic modulation of spike backpropagation in the apical dendrites of hippocampal CA1 pyramidal neurons.

  1997cited by this paper
• Markers of dopamine depletion and compensatory response in striatum and cerebrospinal fluid

  1995cited by this paper
• CSF and plasma concentrations of free norepinephrine, dopamine, 3,4‐dihydroxyphenylacetic acid (DOPAC), 3,4‐dihydroxyphenylalanine (DOPA), and epinephrine in Parkinson's disease.

  1995cited by this paper
• Monoamine metabolites in normal human cerebrospinal fluid and in degenerative diseases of the central nervous system.

  1993cited by this paper
• Monoamines and their metabolites in plasma and lumbar cerebrospinal fluid of Chinese patients with Parkinson's disease.

  1993cited by this paper
• Cholecystokinin in human cerebrospinal fluid: concentrations, dynamics, molecular forms and relationship to fasting and feeding in health, depression and alcoholism.

  1993cited by this paper
• Neuroendocrine regulatory mechanisms in the choroid plexus-cerebrospinal fluid system.

  1992influential reference
• Markers of dopamine metabolism in Parkinson's disease

  1992cited by this paper
• Somatostatin selectively enhances acetylcholine-induced excitations in rat hippocampus and cortex.

  1986cited by this paper
• Cerebrospinal fluid levels of angiotensin-converting enzyme, acetylcholinesterase, and dopamine metabolites in dementia associated with Alzheimer's disease and Parkinson's disease: a correlative study.

  1986cited by this paper
• Value of monoamine metabolite determinations in CSF as an index of their concentrations in rat brain following various pharmacological manipulations.

  1982cited by this paper
• Differential clearance of neurophysin and neurohypophysial peptides from the cerebrospinal fluid in conscious guinea pigs.

  1982cited by this paper
• Comparative anatomy of the serotoninergic systems.

  1981cited by this paper
• The significance of the evolution of the cerebrospinal fluid system.

  1979cited by this paper
• Acetylcholine and choline in cerebrospinal fluid of patients with Parkinson's disease and Huntington's chorea.

  1976cited by this paper
• The neurochemistry of Parkinson's disease: effect of L-dopa therapy.

  1975cited by this paper
• Acetylcholine and Choline

  1974cited by this paper
• The transverse hippocampal slice: a well-defined cortical structure maintained in vitro.

  1971cited by this paper
• THE FINE STRUCTURE OF EPENDYMA IN THE BRAIN OF THE RAT

  1963influential reference

• Intraoperative drug delivery to hindbrain tumours via an injectable hydrogel is well tolerated and confers survival benefit against atypical teratoid/rhabdoid xenografts.

  2026cites this paper
• Motile cilia modulate neuronal and astroglial activity in the zebrafish larval brain.

  2025cites this paper
• A Unified Holographic Framework for neural computation and consciousness: From lipid membranes to the Schumann resonance

  2025cites this paper
• Covalent organic frameworks-based sensors for the detection of neurotransmitters associated with neurogenic diseases

  2025cites this paper
• A synthesized view of the CSF-blood barrier and its surgical implications for aging disorders

  2025cites this paper
• Developmental loss of NMDA receptors results in supernumerary forebrain neurons through delayed maturation of transit-amplifying neuroblasts

  2024cites this paper
• Potential of ex vivo organotypic slice cultures in neuro-oncology.

  2024cites this paper
• Choroid plexus volumes and auditory verbal learning scores are associated with conversion from mild cognitive impairment to Alzheimer's disease

  2024cites this paper
• Human organotypic brain slice cultures: a detailed and improved protocol for preparation and long-term maintenance.

  2024cites this paper
• Intranasal Pathway for Nanoparticles to Enter the Central Nervous System.

  2023cites this paper
• Long-term human organotypic brain slice cultures: a detailed protocol to provide a comprehensive framework for single-neuron and neuronal network investigations

  2023cites this paper
• Loss of NMDA receptor function during development results in decreased KCC2 expression and increased neurons in the zebrafish forebrain

  2023cites this paper
• Gold nanoparticle-enhanced X-ray microtomography of the rodent reveals region-specific cerebrospinal fluid circulation in the brain

  2023cites this paper
• Variation of cerebrospinal fluid in specific regions regulates focality in transcranial direct current stimulation

  2022cites this paper
• Routine culture and study of adult human brain cells from neurosurgical specimens

  2022cites this paper
• Staining of Living Monoaminergic Neurons with 4-[4-(Dimethylamino) Styryl]-N-Methylpyridinium Iodide as a Tool for Studying Their Topography and Functions

  2022cites this paper
• Iron Transport across Brain Barriers: Model and Numerical Parameter Estimation

  2022cites this paper
• GABA excitatory actions in cerebrospinal-fluid contacting neurones of adult mouse spinal cord

  2022cites this paper
• Evidence for PKD2L1‐positive neurons distant from the central canal in the ventromedial spinal cord and medulla of the adult mouse

  2021cites this paper
• Hypothesis on the Endocrine System of the Brain: Evidence for the Regulated Delivery of Neurohormones from the Brain to the Cerebrospinal Fluid and Vice Versa in Neonatal and Prepubertal Periods of Ontogenesis

  2021cites this paper
• Global cerebrospinal fluid circulation mapping using gold nanoparticle enhanced X-ray microtomography reveals region-specific brain and spinal cord CSF pathways

  2021influential citation
• Hypothesis on the Endocrine System of the Brain: Evidence for the Regulated Delivery of Neurohormones from the Brain to the Cerebrospinal Fluid and Vice Versa in Neonatal and Prepubertal Periods of Ontogenesis

  2021cites this paper
• Calcium and Spike Timing-Dependent Plasticity

  2021cites this paper
• Arachnoid membrane as a source of sphingosine-1-phosphate that regulates mouse middle cerebral artery tone

  2021cites this paper
• Biofluidic material-based carriers: Potential systems for crossing cellular barriers.

  2020cites this paper
• Somatic Rhythmic Motion Effective on Peristaltic Circulation of Cerebrospinal Fluid: Hypothesis for Music- and Sport-Based Interventions

  2020cites this paper
• Determination of Neurosteroids in Human Cerebrospinal Fluid in the 21st Century: a Review.

  2020cites this paper
• Human Cerebrospinal Fluid Induces Neuronal Excitability Changes in Resected Human Neocortical and Hippocampal Brain Slices

  2019influential citation
• GABA-b receptors and calcium homeostasis in medullo-spinal CSF-contacting neurons

  2019influential citation
• Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

  2019cites this paper
• The role of motile cilia in the development and physiology of the nervous system

  2019cites this paper
• Ionized calcium in human cerebrospinal fluid and its influence on intrinsic and synaptic excitability of hippocampal pyramidal neurons in the rat

  2019cites this paper
• In vitro neuronal network activity as a new functional diagnostic system to detect effects of Cerebrospinal fluid from autoimmune encephalitis patients

  2019cites this paper