The hypothesis that recurrent inhibition in the hippocampus is mediated by interneurons was tested with simultaneous intracellular recordings from the CA1 region of guinea pig hippocampal slices in vitro. In recordings from 101 pairs of pyramidal cells, no interactions were detected in 87% of the pairs. In 13% of the pyramidal cell pairs, spike trains induced in one cell caused inhibitor postsynaptic potentials (IPSPs) in the second cell. No excitatory interactions were detected. In recordings from 43 pairs of cells, where one cell was a pyramidal cell and the other cell was an interneuron, no interactions were detected in 53% of the pairs. In 30% of the interneuron-pyramidal cell pairs, spike trains elicited from the interneuron caused IPSPs in the pyramidal cell. In 28% of the pairs, spike trains elicited from the pyramidal cell caused excitatory postsynaptic potentials (EPSPs) in the interneurons. In 4% of these pairs, reciprocal interactions were seen, with the pyramidal cell exciting the interneuron and the interneuron inhibiting the pyramidal cell. These results support the hypothesis that inhibitory mediate recurrent inhibition in the hippocampus. However, the data also suggest that the interneurons from which these results were recorded were a subset of inhibitory interneurons distinct from the classical basket cell. These interneurons may mediate both feed-forward and recurrent inhibition in the hippocampus.

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Intracellular recordings were obtained in the vitro slice preparation from neurons of lateral and mesial temporal cortex removed from human epileptics suffering from intractable temporal lobe seizures. Spontaneous rhythmic synaptic events, which were capable of triggering action potential discharge, were observed in many neurons, particularly in mesial tissue slices. Such activity may reflect the epileptogenic capacity of this human cortex.

Intracellular injections of Lucifer Yellow into CA1 pyramidal cells of the in vitro guinea pig hippocampal slice enabled us to examine in detail the morphology of the axons of these neurons. We also recorded the electrophysiological responses of these neurons to alvear stimulation. In our morphological examinations, we found that many axons bifurcate in the alveus, with the major branch projecting caudally toward the subiculum and the second, thinner branch projecting rostrally toward the fimbria. Either axons may bifurcate further to produce several axon branches which follow parallel paths in the alveus. These axons also have local collaterals which project into strata oriens and pyramidale. In addition, a very fine plexus of axonal processes was observed in stratum oriens located largely within the basal dendritic field of the parent cell. Our electrophysiological experiments demonstrated that neurons could be activated antidromically by stimulation of the alveus at sites both rostral ad caudal to the neuron. Weak alvear stimulation occasionally evoked small potentials which appeared similar to fast prepotentials. The local axonal ramifications may be involved in recurrent pathways mediating feedback inhibition and/or excitation. The axonal bifurcations also may provide a basis for understanding the origins of fast prepotentials elicited with antidromic stimulation.

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The in vitro slice technique was used to study neuronal activity in human cortical tissue removed during neurosurgical procedures for intractable epilepsy and in monkey neocortex rendered epileptogenic by injection of alumina gel. In both cases, biopsies were guided by electrocorticographic signs of epileptiform activity. Intracellular recordings were made from 167 neurons in human tissue and from 73 neurons in monkey tissue samples. There was little spontaneous activity in these biopsies and no indication of spontaneous cellular bursting. Stimulation at the pial surface or in white matter evoked synaptically driven activity that was primarily excitatory. Graded bursts of activity could be elicited from some cells, but no all-or-none paroxysmal depolarization shifts were recorded. Inhibitory postsynaptic potentials were relatively rare. Intracellular injections of dye in a small number of neurons revealed no obvious differences between bursting and nonbursting neurons. These in vitro studies of chronic epileptic cortex have thus far provided few clear insights into the basic mechanisms of epilepsy.

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There is a bewildering variety of hyperpolarizing potentials which control activity in hippocampal pyramidal cells. These include an inhibitory postsynaptic potential (IPSP) with early and late components, voltage- and calcium-dependent potassium conductances, a voltage-dependent potassium conductance modulated by muscarinic agents (the M-current), and a complex and poorly understood afterhyperpolarization following epileptiform bursts. In hippocampal CA3 pyramidal cells, mossy fiber stimulation elicits an IPSP which is made up of two readily separable components. Using the in vitro slice preparation, we investigated the underlying ionic basis of these IPSP components and compared them to other hyperpolarizing potentials characteristic of the CA3 neurons. Intracellular recordings were obtained and then tissue was exposed to bathing medium low in chloride concentration or high in potassium concentration; the ion "blockers" EGTA (intracellular); tetraethylammonium (TEA) (intra- and extracellular), and barium and cobalt (extracellular); and the gamma-aminobutyric acid (GABA)/chloride antagonists penicillin, bicuculline and picrotoxin.