title: Complex synaptic current waveforms evoked in hippocampal pyramidal neurons by extracellular stimulation of dentate gyrus.
abstract: Excitatory postsynaptic currents (EPSCs) evoked in hippocampal CA3 pyramidal neurons by extracellular stimulation of the dentate gyrus typically exhibit complex waveforms. They commonly have inflections or notches on the rising phase; the decay phase may exhibit notches or other obvious departures from a simple monoexponential decline; they often display considerable variability in the latency from stimulation to the peak current; and the rise times tend to be long. One hypothesis is that these complex EPSC waveforms might result from excitation via other CA3 pyramidal cells that were recruited antidromically or trans-synaptically by the stimulus due to the complex anatomy of this region. An alternative hypothesis is that EPSC complexity does not emerge from the functional anatomy but rather reflects an unusual physiological property, intrinsic to excitation-secretion coupling in mossy-fiber (mf) synaptic terminals, that causes asynchronous quantal release. We evaluated certain predictions of our anatomic hypothesis by adding a pharmacological agent to the normal bathing medium that should suppress di- or polysynaptic responses. For this purpose we used baclofen (3 microM), a selective agonist for the gamma-aminobutyric acid B receptor. The idea was that baclophen should discriminate against polysynaptic versus monosynaptic inputs by hyperpolarizing the cells, bringing them further from spike threshold and possibly also through inhibitory presynaptic actions. Whole cell recordings were done from visually preselected CA3 pyramidal neurons and EPSCs were evoked by fine bipolar electrodes positioned into the granule cell layer of the dentate. To the extent that the EPSC complexity reflects di- or polysynaptic responses, we predicted 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, and increase the apparent failures in evoked EPSCs. All of these predictions 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 complexity, which also is predicted and easily explained by our anatomic hypothesis. In particular, the results were in accord with the suggestion that stimulation of the dentate gyrus might antidromically stimulate axon collaterals of CA3 neurons that make recurrent synapses onto the recorded cell. We conclude that the overall pattern of results is consistent with expectations based on the functional anatomy. The explanation does not demand a special type of intrinsic asynchronous mechanism for excitation-secretion coupling in the mf synapses.
authors.affiliation: Department of Psychology, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Xiang
authors.forename: T H
authors.initials: TH
authors.lastname: Brown
mesh_terms: D000200:Action Potentials; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D018891:Dentate Gyrus / Q000502:physiology*; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D018755:GABA Agonists; D018080:Receptors, GABA-B; D001418:Baclofen