Cooling Abolishes Neuronal Network Synchronization in Rat Hippocampal Slices.
Abstract number :
1.032
Submission category :
Year :
2001
Submission ID :
180
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
S.P. Javedan, MD, Neurosurgery, Barrow Neurological Institute, Phoenix, AZ; J. Wu, MD PhD, Neurology, Barrow Neurological Insitute, Phoenix, AZ; H.G. Eder, MD, Neurosurgery, Karl-Franzens University, Graz, Austria; K. Smith, MD, Neurosurgery, Barrow Neuro
RATIONALE: Cooling has been discussed as a potential treatment for seizures for decades. Nevertheless, the underlying mechanisms of cooling are unclear. Focal cooling attenuates epileptiform spike trains in slice preparations, but rapid cooling to low temperatures also abolishes normal synaptic transmission. We sought to determine if cooling brain tissue from 34 to 20 C could abolish tetanic stimulation-induced neuronal network synchronization (gamma-oscillation) without blocking normal synaptic transmission.
METHODS: Experiments were performed on transverse hippocampal slices (450-500 uM) from adult and juvenile Sprague-Dawley rats. The air-fluid interface chamber contained artificial cerebrospinal fluid (CSF) comprised of (mM): NaCl 117; KCl 5.4; NaHCO3 26; MgSO4 1.3; NaH2PO4 1.2; CaCl2 2.5; glucose 10. The pH was maintained at 7.4 by continuously bubbling 95% O2 plus 5% CO2. Baseline recording temperature was 34[degree] C. Gamma oscillations were evoked by brief tetanic stimulation at 100 Hz for 200 ms. Cooling was applied by turning off the temperature controller and by exchanging cold Ringer solution (~2 C) perfusion. Chamber temperature was reduced to 20 C within 15 min.
RESULTS: (1) Suprathreshold tetanic stimuli evoked membrane potential oscillation in the gamma frequency range (mean 38.7 Hz, n=21) monitored by simultaneous extra- and intra-cellular voltage recordings. The tetanic gamma oscillations were blocked by bicuculline, a specific GABAA receptor antagonist, indicating that they were mediated by GABAA receptor activation. (2) Cooling of brain slice from 34 to 20 C gradually and reversibly abolished gamma oscillations in all slices tested. Single-pulse-evoked postsynaptic potentials, however, were preserved after cooling in all cases. (3) Latency between the stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r=0.78). (4) Tetanic stimulation at higher intensities elicited not only gamma oscillations, but also epileptiform bursts. Cooling dramatically attenuated the gamma oscillation and abolished epileptiform bursts in a reversible manner.
CONCLUSIONS: Tetanic-induced neuronal network synchronization by GABAA - sensitive gamma-oscillations, is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses the transition from gamma-oscillations to ictal bursting at higher stimulus intensities. These findings suggest that that cooling may disrupt network synchrony necessary for epileptiform activity.
Support: Marjorie Newsome and Sandra Solheim Aiken Fund.
Barrow Neurological Institute Women[ssquote]s Board.