Specific inhibitory synapses shift the balance from feedforward to feedback inhibition of hippocampal CA1 pyramidal cells

Feedforward and feedback inhibition are two fundamental modes of operation widespread in the nervous system. We have functionally identified synaptic connections between rat CA1 hippocampal interneurons of the stratum oriens (SO) and interneurons of the stratum lacunosum moleculare (SLM), which can act as feedback and feedforward interneurons, respectively. The unitary inhibitory postsynaptic currents (uIPSCs) detected with K-gluconate-based patch solution at -50 mV had an amplitude of 20.0 +/- 2.0 pA, rise time 2.2 +/- 0.2 ms, decay time 25 +/- 2.2 ms, jitter 1.4 +/- 0.2 ms (average +/- SEM, n = 39), and were abolished by the gamma-aminobutyric acid (GABA)(A) receptor antagonist 2-(3-carboxypropyl)-3-amino-6-methoxyphenyl-pyridazinium bromide (SR 95531). Post hoc anatomical characterization revealed that all but one of the identified presynaptic neurons were oriens-lacunosum moleculare (O-LM) cells, whereas the postsynaptic neurons were highly heterogeneous, including neurogliaform (n = 4), basket (n = 4), Schaffer collateral-associated (n = 10) and perforant path-associated (n = 9) cells. We investigated the short-term plasticity expressed at these synapses, and found that stimulation at 10-40 Hz resulted in short-term depression of uIPSCs. This short-term plasticity was determined by presynaptic factors and was not target-cell specific. We found that the feedforward inhibition elicited by the direct cortical input including the perforant path onto CA1 pyramidal cells was modulated through the inhibitory synapses we have characterized. Our data show that the inhibitory synapses between interneurons of the SO and SLM shift the balance between feedback and feedforward inhibition onto CA1 pyramidal neurons.