NMDA Receptor Subunit-Dependent [Ca2+] Signaling in Individual Hippocampal Dendritic Spines

Ca2+ influx through synaptic NMDA receptors (NMDA-Rs) triggers a variety of adaptive cellular processes. To probe NMDA-R-mediated [Ca2+] signaling, we used two-photon glutamate uncaging to stimulate NMDA-Rs on individual dendritic spines of CA1 pyramidal neurons in rat brain slices. We measured NMDA-R currents at the soma and NMDA-R-mediated [Ca2+] transients in stimulated spines (Δ[Ca2+]). Uncaging-evoked NMDA-R current amplitudes were independent of the size of the stimulated spine, implying that smaller spines contain higher densities of functional NMDA-Rs. The ratio of Δ[Ca2+] over NMDA-R current was highly variable (factor of 10) across spines, especially for small spines. These differences were not explained by heterogeneity in spine sizes or diffusional coupling between spines and their parent dendrites. In addition, we find that small spines have NMDA-R currents that are sensitive to NMDA-R NR2B subunit-specific antagonists. With block of NR2B-containing receptors, the range of Δ[Ca2+]/NMDA-R current ratios and their average value were much reduced. Our data suggest that individual spines can regulate the subunit composition of their NMDA-Rs and the effective fractional Ca2+ current through these receptors.

• Publication year

  2005

• Venue

  Journal of Neuroscience

• Publication date

  2005-06-29

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.1221-05.2005PMID 15987933PMCID PMC6725044
• 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.

• The Number of Glutamate Receptors Opened by Synaptic Stimulation in Single Hippocampal Spines

  2004influential reference
• Imaging Calcium Concentration Dynamics in Small Neuronal Compartments

  2004influential reference
• Structural basis of long-term potentiation in single dendritic spines

  2004cited by this paper
• NR2B-Containing Receptors Mediate Cross Talk among Hippocampal Synapses

  2004cited by this paper
• State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons.

  2004cited by this paper
• Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity

  2004influential reference
• ScanImage: Flexible software for operating laser scanning microscopes

  2003cited by this paper
• Opposing roles of synaptic and extrasynaptic NMDA receptors in neuronal calcium signalling and BDNF gene regulation.

  2003cited by this paper
• Two Forms of Synaptic Plasticity with Distinct Dependence on Age, Experience, and NMDA Receptor Subtype in Rat Visual Cortex

  2003influential reference
• Plasticity of calcium channels in dendritic spines

  2003influential reference
• The Life Cycle of Ca 2 Ions in Dendritic Spines and

  2002influential reference
• Structure and function of dendritic spines.

  2002cited by this paper
• NMDA receptor subunits: diversity, development and disease.

  2001influential reference
• Ca(2+) signaling in dendritic spines.

  2001influential reference
• Interaction with the NMDA receptor locks CaMKII in an active conformation

  2001cited by this paper
• NMDA receptor antagonists as analgesics: focus on the NR2B subtype.

  2001cited by this paper
• NMDAR EPSC kinetics do not regulate the critical period for LTP at thalamocortical synapses

  2001influential reference
• A use-dependent tyrosine dephosphorylation of NMDA receptors is independent of ion flux

  2001cited by this paper
• Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

  2001influential reference
• Regulation of Spine Calcium Dynamics by Rapid Spine Motility

  2000cited by this paper
• Ligand-gated ion channel interactions with cytoskeletal and signaling proteins.

  2000cited by this paper
• Somatic EPSP amplitude is independent of synapse location in hippocampal pyramidal neurons

  2000cited by this paper
• Diversity and dynamics of dendritic signaling.

  2000cited by this paper
• NMDA Receptor Content of Synapses in Stratum Radiatum of the Hippocampal CA1 Area

  2000cited by this paper
• Mechanisms of Calcium Decay Kinetics in Hippocampal Spines: Role of Spine Calcium Pumps and Calcium Diffusion through the Spine Neck in Biochemical Compartmentalization

  2000cited by this paper
• Long-term potentiation--a decade of progress?

  1999cited by this paper
• Genetic enhancement of learning and memory in mice

  1999influential reference
• Dendritic spine changes associated with hippocampal long-term synaptic plasticity

  1999cited by this paper
• Synaptic calcium transients in single spines indicate that NMDA receptors are not saturated

  1999cited by this paper
• Different modes of expression of AMPA and NMDA receptors in hippocampal synapses

  1999cited by this paper
• Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity.

  1999cited by this paper
• Two-photon imaging in living brain slices.

  1999cited by this paper
• The Incorporation of NMDA Receptors with a Distinct Subunit Composition at Nascent Hippocampal Synapses In Vitro

  1999cited by this paper
• Rapid, experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo

  1999cited by this paper
• Brominated 7-hydroxycoumarin-4-ylmethyls: photolabile protecting groups with biologically useful cross-sections for two photon photolysis.

  1999cited by this paper
• Variability of neurotransmitter concentration and nonsaturation of postsynaptic AMPA receptors at synapses in hippocampal cultures and slices.

  1999cited by this paper
• LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite

  1999cited by this paper
• Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus.

  1998cited by this paper
• Interplay between sodium and calcium dynamics in granule cell presynaptic terminals.

  1997influential reference
• Release and sequestration of calcium by ryanodine‐sensitive stores in rat hippocampal neurones

  1997cited by this paper
• NMDA Channel Regulation by Channel-Associated Protein Tyrosine Kinase Src

  1997cited by this paper
• Direct Measurement of Coupling Between Dendritic Spines and Shafts

  1996influential reference
• Advances in polycystic kidney disease.

  1996cited by this paper
• Ca2+ signaling requirements for long-term depression in the hippocampus.

  1996cited by this paper
• Simultaneous measurement of Ca2+ influx and reversal potentials in recombinant N-methyl-D-aspartate receptor channels.

  1996cited by this paper
• Fractional Ca2+ currents through somatic and dendritic glutamate receptor channels of rat hippocampal CA1 pyramidal neurones.

  1996cited by this paper
• Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice

  1995cited by this paper
• Dendritic spines as basic functional units of neuronal integration

  1995cited by this paper
• Evidence for silent synapses: implications for the expression of LTP.

  1995cited by this paper
• Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.

  1994influential reference
• Changing subunit composition of heteromeric NMDA receptors during development of rat cortex

  1994cited by this paper
• Fractional contribution of calcium to the cation current through glutamate receptor channels.

  1993cited by this paper
• Activity-dependent decrease in NMDA receptor responses during development of the visual cortex.

  1992cited by this paper
• Calcium gradients and buffers in bovine chromaffin cells.

  1992cited by this paper
• Molecular diversity of the NMDA receptor channel

  1992cited by this paper
• Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade.

  1992cited by this paper
• Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses

  1991cited by this paper
• The location and function of NMDA receptors in cat and kitten visual cortex

  1989cited by this paper
• Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics

  1989cited by this paper
• Blockade of "NMDA" receptors disrupts experience-dependent plasticity of kitten striate cortex.

  1987cited by this paper
• Supplemental Data Transient and Persistent Dendritic Spines in the Neocortex In Vivo

  year unknowncited by this paper

• FMRP Controls Neuronal Architecture and Synaptic Content of NMDA Receptors in Cultured Hippocampal Neurons

  2025influential citation
• Optimizing plasticity: the impact of time intervals between priming cTBS and subsequent iTBS on motor-evoked potentials.

  2025cites this paper
• Dynamic control of NMDA receptor Ca2+ permeability by endogenous and synthetic modulators.

  2025cites this paper
• Rules of life at the interface of calcium signaling and mechanobiology

  2025cites this paper
• Kv4.2 Regulates Basal Synaptic Strength by Inhibiting R-Type Calcium Channels in the Hippocampus

  2025cites this paper
• Memory persistence: from fundamental mechanisms to translational opportunities

  2024cites this paper
• Exploring the role of AMPA receptor auxiliary proteins in synaptic functions and diseases

  2024cites this paper
• Astrocyte coverage of excitatory synapses correlates to measures of synapse structure and function in ferret primary visual cortex

  2024cites this paper
• Repeated Morphine Exposure Alters Temporoamonic-CA1 Synaptic Plasticity in Male Rat Hippocampus.

  2024cites this paper
• Serotonin modulates excitatory synapse maturation in the developing prefrontal cortex

  2024cites this paper
• GluN2A or GluN2B subunits of the NMDA receptor contribute to changes in neuronal excitability and impairments in LTP in the hippocampus of aging mice but do not mediate detrimental effects of oligomeric Aβ (1–42)

  2024cites this paper
• Individual NMDA receptor GluN2 subunit signaling domains differentially regulate the postnatal maturation of hippocampal excitatory synaptic transmission and plasticity but not dendritic morphology

  2024cites this paper
• Spatial and temporal aspects of neuronal calcium and sodium signals measured with low-affinity fluorescent indicators

  2023cites this paper
• Voltage tunes mGlu5 receptor function, impacting synaptic transmission

  2023cites this paper
• GRIN2B gene expression is increased in the anterior cingulate cortex in major depression.

  2023cites this paper
• In the fast lane: Receptor trafficking during status epilepticus

  2023cites this paper
• PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTP

  2023cites this paper
• Kv4.2 regulates baseline synaptic strength by inhibiting R-type channel-mediated calcium signaling in the hippocampus

  2023cites this paper
• Introduction: What Are Dendritic Spines?

  2023cites this paper
• Mechanism of Analgesia by Gabapentinoid Drugs: Involvement of Modulation of Synaptogenesis and Trafficking of Glutamate-Gated Ion Channels

  2023cites this paper
• Postsynaptic mitochondria are positioned to support functional diversity of dendritic spines

  2023cites this paper
• Postsynaptic mitochondria are positioned to support functional diversity of dendritic spines

  2023cites this paper
• Electrical properties of dendritic spines.

  2023cites this paper
• The endoplasmic reticulum puts a new spin on synaptic tagging.

  2022cites this paper
• NMDA receptors: Biological properties and their roles in neuropsychiatric disorders

  2022influential citation
• Acrylamide-induced damage to postsynaptic plasticity is CYP2E1 dependent in an SH-SY5Y co-culture system.

  2022cites this paper
• Differential vulnerability of hippocampal CA3-CA1 synapses to Aβ

  2022cites this paper
• Chronic neuronal excitation leads to dual metaplasticity in the signaling for structural long-term potentiation.

  2022cites this paper
• The α2δ-1-NMDA Receptor Complex Is Critically Involved in Neuropathic Pain Development and Gabapentin Therapeutic Actions

  2022cites this paper
• Contribution of individual excitatory synapses on dendritic spines to electrical signaling

  2022cites this paper
• Long-Lasting, Pathway-Specific Impairment of a Novel Form of Spike-Timing-Dependent Long-Term Depression by Neuropathic Pain in the Anterior Cingulate Cortex

  2022cites this paper
• Age‐dependent NMDA receptor function is regulated by the amyloid precursor protein

  2022influential citation
• Aberrant Axo-Axonic Synaptic Reorganization in the Phosphorylated L1-CAM/Calcium Channel Subunit α2δ−1-Containing Central Terminals of Injured c-Fibers in the Spinal Cord of a Neuropathic Pain Model

  2021cites this paper
• The importance of ultrastructural analysis of memory.

  2021cites this paper
• Dopamine and glutamate receptors control social stress-induced striatal ERK1/2 activation.

  2021cites this paper
• Orai1 channels are essential for amplification of glutamate-evoked Ca2+ signals in dendritic spines to regulate working and associative memory

  2021cites this paper
• Chronic neuronal excitation leads to homeostatic suppression of structural long-term potentiation

  2021influential citation
• Orai1 Channels Are Essential for Amplification of Glutamate-Evoked Ca2+ Signals in Dendritic Spines to Regulate Working and Associative Memory

  2020cites this paper
• Ketamine and Calcium Signaling—A Crosstalk for Neuronal Physiology and Pathology

  2020cites this paper
• Possible interplay between the theories of pharmacoresistant epilepsy

  2020cites this paper
• Calcium imaging and optical electrophysiology

  2020cites this paper
• Cortical response selectivity derives from strength in numbers of synapses

  2020cites this paper
• Presynaptic NMDARs cooperate with local spikes toward GABA release from the reciprocal olfactory bulb granule cell spine

  2020cites this paper
• Ketamine inhibits LPS‐mediated BV2 microglial inflammation via NMDA receptor blockage

  2020cites this paper
• Demonstration of critical role of GRIN3A in nicotine dependence through both genetic association and molecular functional studies

  2020cites this paper
• Neural Cell Adhesion Molecule 2 (NCAM2)-Induced c-Src-Dependent Propagation of Submembrane Ca2+ Spikes Along Dendrites Inhibits Synapse Maturation

  2019cites this paper
• Single Synapse LTP: A Matter of Context?

  2019cites this paper
• Cortical neuron response selectivity derives from strength in numbers of synapses

  2019cites this paper
• Probing Single Synapses via the Photolytic Release of Neurotransmitters

  2019cites this paper
• Developmental NMDA receptor dysregulation in the infantile neuronal ceroid lipofuscinosis mouse model

  2019cites this paper
• Abbreviated title : NMDAR activation by spontaneous release 3 4

  2019influential citation
• Electroacupuncture ameliorates learning and memory deficits via hippocampal 5-HT1A receptors and the PKA signaling pathway in rats with ischemic stroke

  2019cites this paper
• Local reciprocal release of GABA from olfactory bulb granule cell spines: Cooperation of 2 conventional release mechanisms and NMDA receptors

  2019cites this paper
• Kilohertz frame-rate two-photon tomography

  2019cites this paper
• Cognitive impairment and autistic-like behaviour in SAPAP4-deficient mice

  2019cites this paper
• Two-Photon Uncaging of Glutamate

  2019cites this paper
• Functional Distinctions between Spine and Dendritic Synapses Made onto Parvalbumin-Positive Interneurons in Mouse Cortex.

  2018cites this paper
• Antioxidant and Cell-Signaling Functions of Hydrogen Sulfide in the Central Nervous System

  2018cites this paper
• Limits on lability: Boundaries of reconsolidation and the relationship to metaplasticity

  2018cites this paper
• Kilohertz frame-rate two-photon tomography

  2018cites this paper
• Propofol attenuates BV2 microglia inflammation via NMDA receptor inhibition.

  2018cites this paper
• neuroprotective effects of dexmedetomidine against isoflurane-induced neuronal injury via glutamate regulation in neonatal rats

  2018cites this paper
• Presynaptic NMDA receptors cooperate with local action potentials to implement activity-dependent GABA release from the reciprocal olfactory bulb granule cell spine

  2018cites this paper
• To the Left or to the Right?

  2018cites this paper
• Advances in the stochastic and deterministic analysis of multistable biochemical networks

  2018cites this paper
• Metaplasticity in the Visual Cortex: Crosstalk Between Visual Experience and Reactive Oxygen Species

  2018cites this paper
• Molecular mechanisms of detection and discrimination of dynamic signals

  2018cites this paper
• Neuromodulatory and metaplastic regulation of long-term synaptic plasticity in the primary visual cortex of adult rats.

  2018cites this paper
• NMDA Receptor Dysregulation by Defective Depalmitoylation in the Infantile Neuronal Ceroid Lipofuscinosis Mouse Model

  2018cites this paper
• Neuroprotective effects of dexmedetomidine against isoflurane-induced neuronal injury via glutamate regulation in neonatal rats

  2018cites this paper
• A machine learning approach for online automated optimization of super-resolution optical microscopy

  2018cites this paper
• Compressed Sensing Beyond the IID and Static Domains: Theory, Algorithms and Applications

  2018cites this paper
• Local reciprocal release of GABA from dendritic spines of olfactory bulb granule cells

  2018cites this paper
• The α2δ-1-NMDA Receptor Complex Is Critically Involved in Neuropathic Pain Development and Gabapentin Therapeutic Actions

  2018cites this paper
• Differential tuning of excitation and inhibition shapes direction selectivity in ferret V1

  2018cites this paper
• Exploring the Ca2+-dependent synaptic dynamics in vibro-dissociated cells.

  2017cites this paper
• Amphetamine and Methamphetamine Increase NMDAR-GluN2B Synaptic Currents in Midbrain Dopamine Neurons

  2017cites this paper
• Optogenetic methods to study lateralization of synaptic function

  2017cites this paper
• Computational investigation of Amyloid-β-induced location- and subunit-specific disturbances of NMDAR at hippocampal dendritic spine in Alzheimer’s disease

  2017cites this paper
• Distance-dependent gradient in NMDAR-driven spine calcium signals along tapering dendrites

  2017cites this paper
• CA1 pyramidal cells have diverse biophysical properties, affected by development, experience, and aging

  2017cites this paper
• Formation and Maintenance of Functional Spines in the Absence of Presynaptic Glutamate Release

  2017cites this paper
• Plasticity and Memory in Cerebral Cortex

  2017cites this paper
• Conditional deletion of Eps8 reduces hippocampal synaptic plasticity and impairs cognitive function

  2017cites this paper
• Numerical analysis of neuronal responses for photolysis of MNI and Rubi caged glutamate

  2017cites this paper
• Optogenetic Methods to Study Lateralized Synaptic Function

  2017cites this paper
• Electrophysiological tagging of ionotropic glutamate receptors

  2016cites this paper
• NMDA Receptors Control Arf6 Activity via BRAG1 and BRAG2 in Spines of Neuronal Dendrites

  2016cites this paper
• Pushing the threshold: How NMDAR antagonists induce homeostasis through protein synthesis to remedy depression.

  2016cites this paper
• N‐Methyl d‐Aspartate Receptor Expression Patterns in the Human Fetal Cerebral Cortex

  2016cites this paper
• Bidirectional Plasticity of Hippocampal Glutamate Receptors Is Central to Expression of Benzodiazepine Withdrawal-Anxiety

  2016cites this paper
• Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus

  2016cites this paper
• Cocaine Self-Administration Elevates GluN2B within dmPFC Mediating Heightened Cue-Elicited Operant Responding

  2016cites this paper
• Basic roles of key molecules connected with NMDAR signaling pathway on regulating learning and memory and synaptic plasticity

  2016cites this paper
• Nanoscale imaging of synapse morphology in the mouse neocortex in vivo by two-photon STED microscopy

  2016cites this paper
• Variations in the stimulus salience of cocaine reward influences drug‐associated contextual memory

  2016cites this paper
• Afferent Input Selects NMDA Receptor Subtype to Determine the Persistency of Hippocampal LTP in Freely Behaving Mice

  2016cites this paper
• Modelling intracellular competition for calcium: kinetic and thermodynamic control of different molecular modes of signal decoding

  2016cites this paper
• Single-Molecule Patch-Clamp FRET Anisotropy Microscopy Studies of NMDA Receptor Ion Channel Activation and Deactivation under Agonist Ligand Binding in Living Cells.

  2016cites this paper
• Simultaneous imaging of structural and functional plasticity in the awake brain

  2015cites this paper