Synaptic activity induces dramatic changes in the geometry of the cell nucleus: interplay between nuclear structure, histone H3 phosphorylation, and nuclear calcium signaling.

TY - JOUR

T1 - Synaptic activity induces dramatic changes in the geometry of the cell nucleus: interplay between nuclear structure, histone H3 phosphorylation, and nuclear calcium signaling.

AU - Wittmann, Malte

AU - Queisser, Gillian

AU - Eder, Anja

AU - Wiegert, J. Simon

AU - Bengtson, C Peter

AU - Hellwig, Andrea

AU - Wittum, Gabriel

AU - Bading, Hilmar

PY - 2009

Y1 - 2009

N2 - Synaptic activity initiates many adaptive responses in neurons. Here we report a novel form of structural plasticity in dissociated hippocampal cultures and slice preparations. Using a recently developed algorithm for three-dimensional image reconstruction and quantitative measurements of cell organelles, we found that many nuclei from hippocampal neurons are highly infolded and form unequally sized nuclear compartments. Nuclear infoldings are dynamic structures, which can radically transform the geometry of the nucleus in response to neuronal activity. Action potential bursting causing synaptic NMDA receptor activation dramatically increases the number of infolded nuclei via a process that requires the ERK-MAP kinase pathway and new protein synthesis. In contrast, death-signaling pathways triggered by extrasynaptic NMDA receptors cause a rapid loss of nuclear infoldings. Compared with near-spherical nuclei, infolded nuclei have a larger surface and increased nuclear pore complex immunoreactivity. Nuclear calcium signals evoked by cytosolic calcium transients are larger in small nuclear compartments than in the large compartments of the same nucleus; moreover, small compartments are more efficient in temporally resolving calcium signals induced by trains of action potentials in the theta frequency range (5 Hz). Synaptic activity-induced phosphorylation of histone H3 on serine 10 was more robust in neurons with infolded nuclei compared with neurons with near-spherical nuclei, suggesting a functional link between nuclear geometry and transcriptional regulation. The translation of synaptic activity-induced signaling events into changes in nuclear geometry facilitates the relay of calcium signals to the nucleus, may lead to the formation of nuclear signaling microdomains, and could enhance signal-regulated transcription.

AB - Synaptic activity initiates many adaptive responses in neurons. Here we report a novel form of structural plasticity in dissociated hippocampal cultures and slice preparations. Using a recently developed algorithm for three-dimensional image reconstruction and quantitative measurements of cell organelles, we found that many nuclei from hippocampal neurons are highly infolded and form unequally sized nuclear compartments. Nuclear infoldings are dynamic structures, which can radically transform the geometry of the nucleus in response to neuronal activity. Action potential bursting causing synaptic NMDA receptor activation dramatically increases the number of infolded nuclei via a process that requires the ERK-MAP kinase pathway and new protein synthesis. In contrast, death-signaling pathways triggered by extrasynaptic NMDA receptors cause a rapid loss of nuclear infoldings. Compared with near-spherical nuclei, infolded nuclei have a larger surface and increased nuclear pore complex immunoreactivity. Nuclear calcium signals evoked by cytosolic calcium transients are larger in small nuclear compartments than in the large compartments of the same nucleus; moreover, small compartments are more efficient in temporally resolving calcium signals induced by trains of action potentials in the theta frequency range (5 Hz). Synaptic activity-induced phosphorylation of histone H3 on serine 10 was more robust in neurons with infolded nuclei compared with neurons with near-spherical nuclei, suggesting a functional link between nuclear geometry and transcriptional regulation. The translation of synaptic activity-induced signaling events into changes in nuclear geometry facilitates the relay of calcium signals to the nucleus, may lead to the formation of nuclear signaling microdomains, and could enhance signal-regulated transcription.

KW - Animals

KW - Cells, Cultured

KW - Rats

KW - Rats, Sprague-Dawley

KW - Phosphorylation

KW - Animals, Newborn

KW - Organ Culture Techniques

KW - Action Potentials/physiology

KW - Synaptic Transmission/physiology

KW - Receptors, N-Methyl-D-Aspartate/metabolism

KW - Nuclear Pore/metabolism

KW - Apoptosis/physiology

KW - Calcium Signaling/physiology

KW - Cell Shape/physiology

KW - Histones/metabolism

KW - Cytosol/metabolism

KW - Cell Compartmentation/physiology

KW - Cell Nucleus/metabolism/ultrastructure

KW - Hippocampus/metabolism/ultrastructure

KW - MAP Kinase Signaling System/physiology

KW - Neurons/metabolism/ultrastructure

KW - Nuclear Envelope/metabolism/ultrastructure

KW - Serine/metabolism

KW - Animals

KW - Cells, Cultured

KW - Rats

KW - Rats, Sprague-Dawley

KW - Phosphorylation

KW - Animals, Newborn

KW - Organ Culture Techniques

KW - Action Potentials/physiology

KW - Synaptic Transmission/physiology

KW - Receptors, N-Methyl-D-Aspartate/metabolism

KW - Nuclear Pore/metabolism

KW - Apoptosis/physiology

KW - Calcium Signaling/physiology

KW - Cell Shape/physiology

KW - Histones/metabolism

KW - Cytosol/metabolism

KW - Cell Compartmentation/physiology

KW - Cell Nucleus/metabolism/ultrastructure

KW - Hippocampus/metabolism/ultrastructure

KW - MAP Kinase Signaling System/physiology

KW - Neurons/metabolism/ultrastructure

KW - Nuclear Envelope/metabolism/ultrastructure

KW - Serine/metabolism

M3 - SCORING: Journal article

VL - 29

SP - 14687

EP - 14700

JO - J NEUROSCI

JF - J NEUROSCI

SN - 0270-6474

IS - 47

M1 - 47

ER -