COMPLEX SYNAPTIC CURRENT WAVE-FORMS EVOKED IN HIPPOCAMPAL PYRAMIDAL NEURONS BY EXTRACELLULAR STIMULATION OF DENTATE GYRUS

Excitatory postsynaptic currents (EPSCs) evoked in hippocampal CA3 pyr amidal neurons by extracellular stimulation of the dentate gyrus typic ally exhibit complex waveforms. They commonly have inflections or notc hes on the rising phase; the decay phase may exhibit notches or other obvious departures from a simple monoexponential decline; they often d isplay considerable variability in the latency from stimulation to the peak current; and the rise times tend to be long. One hypothesis is t hat these complex EPSC waveforms might result from excitation via othe r CA3 pyramidal cells that were recruited antidromically or trans-syna ptically by the stimulus due to the complex anatomy of this region. An alternative hypothesis is that EPSC complexity does not emerge from t he functional anatomy but rather reflects an unusual physiological pro perty, intrinsic to excitation-secretion coupling in messy-fiber (mf) synaptic terminals, that causes asynchronous quantal release. We evalu ated certain predictions of our anatomic hypothesis by adding a pharma cological agent to the normal bathing medium that should suppress di-o r polysynaptic responses. For this purpose we used baclofen (3 mu M), a selective agonist for the gamma-aminobutyric acid B receptor. The id ea was that baclophen should discriminate against polysynaptic versus monosynaptic inputs by hyperpolarizing the cells, bringing them furthe r from spike threshold and possibly also through inhibitory presynapti c actions. Whole cell recordings were done from visually preselected C A3 pyramidal neurons and EPSCs were evoked by fine bipolar electrodes positioned into the granule cell layer of the dentate. To the extent t hat the EPSC complexity reflects di-or polysynaptic responses, we pred icted baclofen to reduce the number of notches on the rising and decay phases, reduce the variance in latency to peak of the EPSCs, decrease the amplitudes and rise times of the individual and averaged EPSCs, a nd increase the apparent failures in evoked EPSCs. All of these predic tions were confirmed, in support of the hypothesis that these complex EPSC waveforms commonly reflect di-or polysynaptic responses. We also documented a distinctly different, intermittent, form of EPSC complexi ty, which also is predicted and easily explained by our anatomic hypot hesis. In particular, the results were in accord with the suggestion t hat stimulation of the dentate gyrus might antidromically stimulate ax on collaterals of CA3 neurons that make recurrent synapses onto the re corded cell. We conclude that the overall pattern of results is consis tent with expectations based on the functional anatomy. The explanatio n does not demand a special type of intrinsic asynchronous mechanism f or excitation-secretion coupling in the mf synapses.