• H E Scharfman.
• Neurology Research Center, Helen Hayes Hospital, West Haverstraw, NY 10993-1195, USA.
• Neuroscience. 1996 Jun 1; 72 (3): 655668655-68.

AbstractUnder control conditions, stimulation of area CA3 pyramidal cells in slices can produce inhibitory postsynaptic potentials in granule cells by a polysynaptic pathway that is likely to involve hilar neurons [Muller W. and Misgeld U. (1990) J. Neurophysiol. 64, 46-56; Muller W. and Misgeld U. (1991) J. Neurophysiol. 65, 141-147; Scharfman H. E. (1993) Neurosci. Lett. 156, 61-66; Scharfman H. F. (1994) Neurosci. Lett. 168, 29-33]. When slices are disinhibited, excitatory postsynaptic potentials occur after the same stimulus [Sharfman H. E. (1994) J. Neurosci. 14, 6041-6057]. The excitatory postsynaptic potentials are likely to be mediated by pyramidal cells that innervate hilar mossy cells, which in turn innervate granule cells. [Scharfman H. F. (1994) J. Neurosci 14, 6041-6057]. These pathways are potentially important, because they could provide positive or negative feedback from area CA3 to the dentate gyrus. However, it is not clear when the CA3-mossy cell-granule cell excitatory pathway operates, because to date it has only been described in detail when GABA(A) receptors are blocked throughout the entire slice [Scharfman H. E. (1994) J. Neurosci 14, 6041-6057]. Furthermore, the monosynaptic excitatory synaptic connections between these cells have only been observed in the presence of bicuculline [Scharfman H. F. (1994) J. Neurophysiol. 72, 2167-2180; Scharfman H. E. (1995) J. Neurophysiol. 74, 179-194]. Yet in vivo data suggest that a CA3-mossy cell-granule cell excitatory pathway may be active under some physiological conditions, because granule cells discharge in association with sharp wave population bursts of CA3 [Ylinen A., et al. (1995) Hippocampus 5, 78-90]. To address whether the CA3-mossy cell-granule cell pathway occurs without global disinhibition of the slice, and where in the network disinhibition may be required, the effects of area CA3 stimulation on granule cells was examined after focal application of the GABAA receptor antagonist bicuculline to restricted areas of hippocampal slices. A micropipette containing 1 mM bicuculline was placed transiently either (i) in the area CA3 cell layer, (ii) the granule cell layer, (iii) the hilus, or (iv) more than one site in succession. If a small segment of the CA3 pyramidal cell layer or the hilus was disinhibited, or bicuculline was applied to both regions, area CA3 stimulation still evoked inhibitory postsynaptic potentials in granule cells. In fact, inhibitory postsynaptic potentials were enhanced under these conditions, probably because excitation of inhibitory cells was increased. When bicuculline was applied just to the area near an impaled granule cell, all inhibitory postsynaptic potentials evoked in that cell were blocked, but no underlying excitatory postsynaptic potential was uncovered. If bicuculline was applied focally to either area CA3 or the hilus and the impaled granule cell, CA3 stimulation subsequently evoked excitatory postsynaptic potentials in that granule cell, presumably because excitatory neurons innervating granule cells were disinhibited while the effects of inhibitory cells on granule cells were blocked. Excitatory postsynaptic potentials were produced without bicuculline application in three of seven cells, simply by stimulating the fimbria repetitively. Thus, if bicuculline is applied to different sites in the slice, different effects occur on the inhibitory postsynaptic potentials of granule cells that are evoked by a fimbria stimulus. If bicuculline is applied to both the granule cell soma and either area CA3 or the hilus, inhibitory postsynaptic potentials are reduced, and reveal that excitatory postsynaptic potentials can be produced by the same stimulus. (ABSTRACT TRUNCATED)

12 keywords...

hide…