GABA(A) CURRENTS IN IMMATURE DENTATE GYRUS GRANULE CELLS

We used whole cell patch clamp and gramicidin perforated patch recordi ngs in hippocampal slices to study gamma-aminobutyric acid (GABA) curr ents in granule cells (GCs) from juvenile rat dentate gyms (DG). GCs a re generated postnatally and asynchronously such that they can be dete cted at different stages of their maturation in DG within the first mo nth. 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 GAB A currents evoked in GCs by medial perforant path stimulation are comp ared. The first, pharmacologically isolated by glutamate receptor bloc kade, is the product of direct activation of GABA interneurons with mo nosynaptic input to the recorded GC (monosynaptic GABA(A)). Monosynapt ic GABA(A) displays slight outward rectification of its current-voltag e relation, is 97% eliminated by 10 mu M bicuculline and coincides tem porally with the excitatory components of GC postsynaptic currents as has been described for GABA(A) currents in other brain regions. The se cond is a novel GABA response that is detectable in 10 mu M bicucullin e and is present on GCs only at the earliest stages of their maturatio n. Unlike monosynaptic GABA(A), this transient GABA is eliminated by g lutamate receptor blockade and hence is likely to be generated by inte rneurons activated via an intervening,glutamatergic synapse (polysynap tically). It is predominantly chloride mediated, has a relative bicarb onate/chloride permeability ratio of 26%, and is unchanged by bath-app lied 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 G ABA(A), BMIR-GABA(A) has a later peak, slower time course of decay, an d marked outward rectification. Its reversal potential is 7-8 mV depol arized to that of monosynaptic GABA(A) whether recorded in whole cell or with gramicidin perforated patch to preserve native internal chlori de concentration. Together these data may suggest that BMIR-GABA(A) is evoked by an anatomically segregated population of interneurons activ ating a unique, developmentally regulated GABA(A) receptor. Further, t he transient nature of this current coupled with its temporal characte ristics that preclude overlap with the excitatory components of the sy naptic response are consistent with a role that is trophic or signalin g rather than primarily inhibitory.