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

Maturation of GABAA/benzodiazepine receptors is associated with changes in their subunit composition. We have investigated whether these changes are accompanied by a developmental modification in the kinetic properties of miniature IPSCs (mIPSCs) and sensitivity to midazolam, a benzodiazepine agonist. In the presence of TTX (10 microM) and excitatory amino acid antagonists, AP5 (50 microM) and CNQX (50 microM), we whole-cell recorded mIPSCs in CA3 cells of hippocampal slices of adult and young (4-8 days) rats. mIPSCs were mediated by GABAA receptors as they were suppressed by bicuculline (10 microM). In both the adult and young rats, mIPSCs were similar in amplitude and kinetic properties. However, the mIPSCs frequency markedly increased with age from 4+/-3 Hz in the young rats to 20+/-9 Hz in the adult rats. In both age groups, midazolam (0.01 microM(-10) microM) and pentobarbital (30 microM) did not affect the amplitude, frequency and rise time of the mIPSCs but they increased to a similar extent their decay time constant. The current responses to isoguvacine, a GABAA agonist, were potentiated by 0.1 microM midazolam in both age groups. It is concluded that in immature and adult rats, synaptic GABAA receptors of CA3 were not different in their kinetic properties and sensitivity to midazolam.