BILIRUBIN REVERSIBLY REDUCES SYNAPTIC TRANSMISSION IN RAT HIPPOCAMPAL SLICES

Abstract

Bilirubin increases latencies and reduces amplitudes in the auditory brainstem response (ABR). However, the basic mechanisms involved are not known. The aim of the present study was to investigate the neurotoxic effects of bilirubin on synaptic transmission in an in vitro system. Hippocampal slices were prepared from 5-7 weeks old male Sprague-Dawley rats and incubated at 30-33°C in an artificial cerebrospinal fluid equilibrated with 95% O2 and 5% CO2 to pH 7.4. We stimulated the Schaffer collaterals of the CA3 cells. Recordings were made of the amplitudes of the presynaptic fibre volley (PV) and the field excitatory postsynaptic potential (EPSP) in the apical dendritic layer of the CA1 region, and of the population spike (PS) in the corresponding cell body layer. The slices were exposed to bilirubin at concentrations up to 1mM, in an 8:1 molar ratio with bovine serum albumin (BSA). Over periods of 30-120 minutes a gradual reduction in the field EPSP amplitude was noted. In parallel with this the peak latency of the PS increased. The stimulus/response relationships were examined with stimulus voltage from 1.0 to 3.4V. Bilirubin caused the PV/EPSP curve to shift to the right, while the EPSP/PS curve shifted to the left. These changes were reversed when bilirubin was removed from the perfusion fluid. The effect of bilirubin on rat hippocampal slices consists of a gradual and reversible decrease in synaptic transmission. This is consistent with the findings reported from ABR studies.