Presynaptic [GABA.sub.A] receptors enhance transmission and LTP induction at hippocampal mossy fiber synapses

Presynaptic [GABA.sub.A] receptors ([GABA.sub.A]Rs) occur at hippocampal mossy fiber synapses. Whether and how they modulate orthodromic signaling to postsynaptic targets is poorly understood. We found that an endogenous neurosteroid that is selective for high-affinity 8 subunit-containing [GABA.sub.A]Rs depolarized rat mossy fiber boutons, enhanced action potential- dependent [Ca.sup.2+] transients and facilitated glutamatergic transmission to pyramidal neurons. Conversely, blocking [GABA.sub.A]Rs hyperpolarized mossy fiber boutons, increased their input resistance, decreased spike width and attenuated action potential-dependent presynaptic [Ca.sup.2+] transients, indicating that a subset of presynaptic GABA receptors are tonically active. Blocking [GABA.sub.A]Rs also interfered with the induction of long-term potentiation at mossy fiber-CA3 synapses. Presynaptic [GABA.sub.A]Rs therefore facilitate information flow to the hippocampus both directly and by enhancing LTP.