Extracellular acidosis and high levels of carbon dioxide suppress synaptic transmission and prevent the induction of long-term potentiation in the CA1 region of rat hippocampal slices.
Long-term potentiation (LTP) is a long-lasting increase in synaptic strength induced by high frequency stimulation. LTP may participate in learning and memory formation. In many synaptic systems, LTP is dependent on intact function of N-methyl-D-aspartate (NMDA) receptors. NMDA receptors may be inhibited in different conditions involving also extracellular acidosis. A decrease in the extracellular pH accompanies many pathological states such as ischemia, hypoxia, and the CNS injury. The study was designed to determine whether comparable extracellular acid-base imbalances are able to interfere with the LTP induction. Hippocampal slices from adult rats were stimulated with high frequency stimulation (1 x 100 Hz/1 s) at Schaffer collateral-commissural synaptic system in the environment with different pH (6.7-7.8) and the field responses were recorded in CA1. Acidosis was achieved by supplying excessive CO2 or by HCO3-decrease in standard bicarbonate-containing buffer or by a direct acidification of the buffer containing Na-HEPES. Invariably, all forms of acidification suppressed the efficacy of normal, low frequency synaptic transmission and prevented the induction of LTP in a reversible manner; i.e., after reperfusion of the slices at pH 7.3 and restimulation, there was a return of synaptic transmission back to baseline, and a significant amount of LTP occurred. In contrast, alkalization to pH 7.8, although enhancing synaptic transmission efficacy, did not further increase the LTP magnitude compared to control environment with pH 7.3. The results suggest that extracellular acidosis associated with several pathological conditions in the CNS may significantly diminish the LTP induction, and thus negatively affect all physiological processes that utilize LTP.
Velísek
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Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. velisek@aecom.yu.edu
D000138:Acidosis / Q000139:chemically induced*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D002021:Buffers; D002245:Carbon Dioxide / Q000494:pharmacology*; D002555:Cerebrospinal Fluid; D003864:Depression, Chemical; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D001639:Bicarbonates; D002021:Buffers; D002245:Carbon Dioxide