GABAA currents in immature dentate gyrus granule cells

We used whole cell patch clamp and gramicidin perforated patch recordings in hippocampal slices to study gamma-aminobutyric acid (GABA) currents in granule cells (GCs) from juvenile rat dentate gyms (DG). GCs are generated postnatally and asynchronously such that they can be detected at different stages of their maturation in DG within the first month. In contrast, inhibitory interneurons are generated embryonically, and their circuitry is well developed even as their target GCs and GC excitatory connections are still being formed. In this study, two GABA currents evoked in GCs by medial perforant path stimulation are compared. The first, pharmacologically isolated by glutamate receptor blockade, is the product of direct activation of GABA interneurons with monosynaptic input to the recorded GC (monosynaptic GABA(A)). Monosynaptic GABA(A) displays slight outward rectification of its current-voltage relation, is 97% eliminated by 10 mu M bicuculline and coincides temporally with the excitatory components of GC postsynaptic currents as has been described for GABA(A) currents in other brain regions. The second is a novel GABA response that is detectable in 10 mu M bicuculline and is present on GCs only at the earliest stages of their maturation. Unlike monosynaptic GABA(A), this transient GABA is eliminated by glutamate receptor blockade and hence is likely to be generated by interneurons activated via an intervening,glutamatergic synapse (polysynaptically). It is predominantly chloride mediated, has a relative bicarbonate/chloride permeability ratio of 26%, and is unchanged by bath-applied saclofen and strychnine or by intracellular calcium chelation. It is 97% antagonized by 100 mu M picrotoxin and 99% antagonized by 100 mu M bicuculline. This current is thus a relatively bicuculline (BMI) resistant GABA(A) current (BMIR-GABA(A)). Compared with monosynaptic GABA(A), BMIR-GABA(A) has a later peak, slower time course of decay, and marked outward rectification. Its reversal potential is 7-8 mV depolarized to that of monosynaptic GABA(A) whether recorded in whole cell or with gramicidin perforated patch to preserve native internal chloride concentration. Together these data may suggest that BMIR-GABA(A) is evoked by an anatomically segregated population of interneurons activating a unique, developmentally regulated GABA(A) receptor. Further, the transient nature of this current coupled with its temporal characteristics that preclude overlap with the excitatory components of the synaptic response are consistent with a role that is trophic or signaling rather than primarily inhibitory.