Network properties of the hippocampus emerge from the interaction of princi
pal cells and a heterogeneous population of interneurons expressing gamma-a
minobutyric acid (GABA). To understand these interactions, the synaptic con
nections of different types of interneurons need to be elucidated. Here we
describe a type of inhibitory interneuron of the hippocampal CA3 region tha
t has an axon coaligned with the mossy fibers. Whole-cell patch-clamp recor
dings, in combination with intracellular biocytin filling, were made from n
onpyramidal cells of the stratum lucidum under visual control. Mossy fiber-
associated (MFA) interneurons generated brief action potentials followed by
a prominent after-hyperpolarization. Subsequent visualization revealed an
extensive axonal arbor which was preferentially located in the stratum luci
dum of CA3 and often invaded the hilus, The dendrites of MFA interneurons w
ere mainly located in the strata radiatum and oriens, suggesting that these
cells are primarily activated by associational and commissural fibers. Ele
ctron microscopic analysis showed that axon terminals of MFA interneurons e
stablished symmetric synaptic contacts predominantly on proximal apical den
dritic shafts. and to a lesser degree, on somata of pyramidal cells. Synapt
ic contacts were also found on GABAergic interneurons of the CA3 region and
putative mossy cells of the hilus, Inhibitory postsynaptic currents (IPSCs
) elicited by MFA interneurons in simultaneously recorded pyramidal cells h
ad fast kinetics (half duration, 3.6 ms) and were blocked by the GABA(A) re
ceptor antagonist bicuculline, Thus, MFA interneurons are GABAergic cells i
n a position to selectively suppress the mossy fiber input, an important re
quirement for the recall of memory traces from the CA3 network.