Developmental study of miniature IPSCs of CA3 hippocampal cells: modulation by midazolam

Maturation of GABA(A)/benzodiazepine receptors is associated with changes i n their subunit composition. We have investigated whether these changes are accompanied by a developmental modification in the kinetic properties of m iniature IPSCs (mIPSCs) and sensitivity to midazolam, a benzodiazepine agon ist. In the presence of TTX (10 mu M) and excitatory amino acid antagonists , AP5 (50 mu M) and CNQX (50 mu M), we whole-cell recorded mIPSCs in CA3 ce lls of hippocampal slices of adult and young (4-8 days) rats. mIPSCs were m ediated by GABA(A) receptors as they were suppressed by bicuculline (10 mu M). In both the adult and young rats, mlPSCs were similar in amplitude and kinetic properties. However, the mIPSCs frequency markedly increased with a ge from 4 +/- 3 Hz in the young rats to 20 +/- 9 Hz in the adult rats. In b oth age groups, midazolam (0.01 mu M-10 mu M) and pentobarbital (30 mu M) d id not affect the amplitude, frequency and rise time of the mIPSCs but they increased to a similar extent their decay time constant. The current respo nses to isoguvacine, a GABA(A) agonist, were potentiated by 0.1 mu M midazo lam in both age groups. It is concluded that in immature and adult rats, sy naptic GABA(A) receptors of CA3 were not different in their kinetic propert ies and sensitivity to midazolam. (C) 1999 Published by Elsevier Science B. V. All rights reserved.