Opposing modifications in intrinsic currents and synaptic inputs in post-traumatic mossy cells

TY - JOUR

T1 - Opposing modifications in intrinsic currents and synaptic inputs in post-traumatic mossy cells

T2 - evidence for single-cell homeostasis in a hyperexcitable network

AU - Howard, Allyson L

AU - Neu, Axel

AU - Morgan, Robert J

AU - Echegoyen, Julio C

AU - Soltesz, Ivan

PY - 2007/3/1

Y1 - 2007/3/1

N2 - Recent experimental and modeling results demonstrated that surviving mossy cells in the dentate gyrus play key roles in the generation of network hyperexcitability. Here we examined if mossy cells exhibit long-term plasticity in the posttraumatic, hyperexcitable dentate gyrus. Mossy cells 1 wk after fluid percussion head injury did not show alterations in their current-firing frequency (I-F) and current-membrane voltage (I-V) relationships. In spite of the unchanged I-F and I-V curves, mossy cells showed extensive modifications in Na(+), K(+) and h-currents, indicating the coordinated nature of these opposing modifications. Computational experiments in a realistic large-scale model of the dentate gyrus demonstrated that individually, these perturbations could significantly affect network activity. Synaptic inputs also displayed systematic, opposing modifications. Miniature excitatory postsynaptic current (EPSC) amplitudes were decreased, whereas miniature inhibitory postsynaptic current (IPSC) amplitudes were increased as expected from a homeostatic response to network hyperexcitability. In addition, opposing alterations in miniature and spontaneous synaptic event frequencies and amplitudes were observed for both EPSCs and IPSCs. Despite extensive changes in synaptic inputs, cannabinoid-mediated depolarization-induced suppression of inhibition was not altered in posttraumatic mossy cells. These data demonstrate that many intrinsic and synaptic properties of mossy cells undergo highly specific, long-term alterations after traumatic brain injury. The systematic nature of such extensive and opposing alterations suggests that single-cell properties are significantly influenced by homeostatic mechanisms in hyperexcitable circuits.

AB - Recent experimental and modeling results demonstrated that surviving mossy cells in the dentate gyrus play key roles in the generation of network hyperexcitability. Here we examined if mossy cells exhibit long-term plasticity in the posttraumatic, hyperexcitable dentate gyrus. Mossy cells 1 wk after fluid percussion head injury did not show alterations in their current-firing frequency (I-F) and current-membrane voltage (I-V) relationships. In spite of the unchanged I-F and I-V curves, mossy cells showed extensive modifications in Na(+), K(+) and h-currents, indicating the coordinated nature of these opposing modifications. Computational experiments in a realistic large-scale model of the dentate gyrus demonstrated that individually, these perturbations could significantly affect network activity. Synaptic inputs also displayed systematic, opposing modifications. Miniature excitatory postsynaptic current (EPSC) amplitudes were decreased, whereas miniature inhibitory postsynaptic current (IPSC) amplitudes were increased as expected from a homeostatic response to network hyperexcitability. In addition, opposing alterations in miniature and spontaneous synaptic event frequencies and amplitudes were observed for both EPSCs and IPSCs. Despite extensive changes in synaptic inputs, cannabinoid-mediated depolarization-induced suppression of inhibition was not altered in posttraumatic mossy cells. These data demonstrate that many intrinsic and synaptic properties of mossy cells undergo highly specific, long-term alterations after traumatic brain injury. The systematic nature of such extensive and opposing alterations suggests that single-cell properties are significantly influenced by homeostatic mechanisms in hyperexcitable circuits.

KW - Animals

KW - Animals, Newborn

KW - Computer Simulation

KW - Craniocerebral Trauma

KW - Disease Models, Animal

KW - Dose-Response Relationship, Radiation

KW - Drug Interactions

KW - Electric Stimulation

KW - Membrane Potentials

KW - Models, Neurological

KW - Mossy Fibers, Hippocampal

KW - Nerve Net

KW - Neurons

KW - Patch-Clamp Techniques

KW - Piperidines

KW - Potassium Channel Blockers

KW - Pyrazoles

KW - Pyrimidines

KW - Rats

KW - Sodium Channel Blockers

KW - Tetraethylammonium

KW - Tetrodotoxin

U2 - 10.1152/jn.00509.2006

DO - 10.1152/jn.00509.2006

M3 - SCORING: Journal article

C2 - 16943315

VL - 97

SP - 2394

EP - 2409

JO - J NEUROPHYSIOL

JF - J NEUROPHYSIOL

SN - 0022-3077

IS - 3

ER -