PHYSIOLOGY AND PHARMACOLOGY OF UNITARY SYNAPTIC CONNECTIONS BETWEEN PAIRS OF CELLS IN AREAS CA3 AND CA1 OF RAT HIPPOCAMPAL SLICE CULTURES

1. Paired intracellular recordings were mode in rat hippocampal slice cultures, with the use of either sharp microelectrodes or the whole ce ll configuration of thr patch-clamp technique. Unitary synaptic connec tions were studied between pyramidal and nonpyramidal cells within and between areas CA1 and CA3. 2. Monosynaptic excitatory synaptic respon ses between CA3 pyramidal neurons were found in 56% of cell pairs (n = 91, 28 postsynaptic cells). Monosynaptic connections from a CA3 cell to a CA1 cell were observed in 76% of cell pairs (n = 125, 26 postsyna ptic cells). but from CA1 to CA3 neurons in only 8% of cell pairs (n = 13, 13 postsynaptic cells). Monosynaptic excitatory connections were found in only 16% of CA1/CA1 cell pairs (n = 25, 10 postsynaptic cells ). 3. Disynaptic inhibition was commonly observed between CA3 cell pai rs (43%), but rarely found between CA3-CA1 pyramidal cell pairs (2%). In 50% of CA3 pyramidal cell pairs. synchronous inhibitory postsynapti c potentials (IPSPs) in both cells could be triggered by an action pot ential in one pyramidal cell. Reciprocal monosynaptic connections were found between 75% of interneuron and pyramidal cell pairs within area CA3. 4. The latency of monosynaptic CA3- to CA1-cell responses was si gnificantly longer than for responses between two CA3 cells. Within ar ea CA3 the latencies for inhibitory synaptic responses between interne urons and pyramidal cells were significantly shorter than those for ex citatory responses between pyramidal cells, Monosynaptic excitatory po stsynaptic potentials (EPSPs) in interneurons had a significantly shor ter time-to-peak than those recorded in pyramidal neurons. 5. 6-Cyano- 7-nitroquinoxaline-2,3-dione (CNQX)- and D-2-amino-5-phosphonovalerate (APS)-sensitive components were identified in unitary monosynaptic EP SPs in CA3-CA3 and CA3-CA1 pyramidal cell pairs. The CNQX-sensitive co mponent had a mean time-to-peak and duration of 6.2 +/- 0.3 (SE) ms an d 61.2 +/- 2.0 ms, respectively, and an amplitude of similar to 1 mV ( n = 93). The APS-sensitive component of EPSPs was only detected when t he cell was depolarized with respect to the resting potential, had a m ean rime-to-peak of 41 +/- 5 ms and duration of 121 +/- 1.1 ms (n = 6) , and increased in amplitude with postsynaptic depolarization. 6. Unit ary monosynaptic IPSPs between an interneuron and a pyramidal cell had a mean amplitude of similar to 1 mV and were fully blocked by gamma-a minobutyric acid-A (GABA(A)) receptor antagonists (n = 3). 7. Unitary inhibitory responses were found only within, but not between, areas CA 3 or CA1. Isolated IPSPs could be evoked in pairs of pyramidal cells i n the presence of excitatory amino acid receptor antagonists only when the extracellular stimulating electrode was located within the same h ippocampal field as the recorded cells. A zone of similar to 380 mu m could be delimited at the border between areas CA3 and CA1, within whi ch stimulation evoked IPSPs in both hippocampal fields. 8. Excitatory synapses formed by CA3 pyramidal cells with either CA3 or CA1 cells we re equally effective, and it can be estimated that 5-10 CA3 cells must be active within 50 ms to activate a common postsynaptic pyramidal ce ll. In contrast, discharge in a single interneuron is sufficient to in hibit action potentials in a postsynaptic pyramidal cell.