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Received June 18, 2003
Revised July 18, 2003
Accepted after revision October 28, 2003
1 NICHD-LCSN
* To whom correspondence should be addressed. E-mail: lawrence{at}codon.nih.gov.
Recent anatomical evidence that inhibitory interneurons receive approximately ten times more synapses from mossy fibers than do principal neurons (Acsady et al., 1998) has led to the reexamination of the extent to which interneurons are involved in CA3 network excitability. Although many of the anatomical and physiological properties of mossy fiber-CA3 interneuron synapses have been previously described (Acsady et al., 1998; Toth et al., 2000), an investigation into the quantal nature of transmission at this synapse has not yet been conducted. Here, we employed variance-mean analysis to compare the release probability, quantal size (q), and number of release sites (n) at mossy fiber target neurons in CA3. At 6 of 7 interneuron synapses in which a high concentration of calcium was experimentally imposed, the variance-mean relationship could be approximated by a parabola. Estimates of n were 1-2, and the weighted release probability in normal calcium conditions ranged from 0.34-0.51. At pyramidal cell synapses, the variance-mean relationship approximated a linear relationship, suggesting that release probability was significantly lower. The weighted quantal amplitude was similar at interneuron synapses and pyramidal cell synapses, although the variability in quantal amplitude was larger at interneuron synapses. Mossy fiber transmission at CA3 interneuron synapses can be explained by a lower number of release sites, a broader range of release probabilities, and larger range of quantal amplitudes than at CA3 pyramidal synapses. Finally, quantal events onto interneurons elicited spike transmission, owing in part to the more depolarized membrane potential than pyramidal cells. These results suggest that although mossy fiber synapses onto pyramidal cells are associated with a larger number of release sites per synapse, the higher connectivity, higher initial release probability, and larger relative impact per quantum onto CA3 interneurons generate strong feedforward inhibition at physiological firing frequencies of dentate granule cells. Given the central role of CA3 interneurons in mossy fiber synaptic transmission, these details of mossy fiber synaptic transmission should provide insight into CA3 network dynamics under both physiological and pathophysiological circumstances.
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