Changes in the Calcium Dependence of Glutamate Transmission in the Hippocampal CA1 Region After Brief Hypoxia-Hypoglycemia

Abstract

Using the model of hypoxia-hypoglycemia (HH) in rat brain slices, we asked whether glutamate transmission is altered following a brief HH episode. The HH challenge was conducted by exposing slices to a glucose-free medium aerated with 95% N2-5% CO2, for approximately 4 min, and glutamate transmission in the hippocampal CA1 region was monitored at different post HH times. In slices examined </=8 h post HH, CA1 synaptic field potentials are comparable in amplitude to controls, but are less sensitive to experimental manipulations designed to attenuate intracellular Ca2+ signals, as compared with controls. Reducing calcium influx, by applying a nonspecific calcium channel blocker Co2+ or lowering external Ca2+, attenuated CA1 synaptic potentials much less in challenged slices than in controls. Buffering intracellular Ca2+ by bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid-AM (BAPTA-AM) attenuated CA1 synaptic potentials in control but not in slices post HH. Furthermore, minimally evoked excitatory postsynaptic currents displayed a lower failure rate in post-hypoxic CA1 neurons compared with controls. Based on these convergent observations, we suggest that evoked CA1 glutamate transmission is altered in the first several hours after brief hypoxia, likely resulting from alterations in intracellular Ca2+ homeostasis and/or Ca2+-dependent processes governing transmitter release.

The Role of Extracellular Adenosine in Regulating Mossy Fiber Synaptic Plasticity

“…The abovementioned putative hypoxia of slices in a submerged chamber or during preparation perhaps could have increased release probability. It has been demonstrated that glutamate release can be persistently increased in hippocampal slices after even a brief episode of severe hypoxia (Hsu and Huang, 1997;Ouanonou et al, 1999).…”

A1 adenosine receptors mediate hypoglycemia-induced neuronal injury

“…Because most studies involving hypoglycemia use glucose deprivation in combination with other insults (Vannucci & Yager 1992, Yager et al 1992, Ouanonou et al 1999, Breder et al 2000, Tekkok et al 2002, it is difficult to determine direct and indirect effects. In contrast, the data we present here represent effects of hypoglycemia only, using a single population of neurons, wherein direct action of glucose deprivation can more readily be observed.…”

Cellular mechanisms of cobalt‐induced hippocampal epileptiform discharges

“…A glass suction pipet (diameter of 10 mm) was used to transfer slices. We have previously shown that the slice transfer procedure causes no evident alterations in synaptic and intracellular activities of hippocampal pyramidal neurons (Ouanonou et al, 1999). Slice transfer alone (without cobalt incubation) did not induce epileptiform discharges (n = 10 slices).…”