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J Physiol Volume 586, Number 11, 2695-2712, June 1, 2008 DOI: 10.1113/jphysiol.2008.152751
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NEUROSCIENCE

Coincidence detection of convergent perforant path and mossy fibre inputs by CA3 interneurons

 Eduardo Calixto1, Emilio J. Galván2, J. Patrick Card2 and Germán Barrionuevo2

1 División de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente, México City, México
2 Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA

We performed whole-cell recordings from CA3 s. radiatum (R) and s. lacunosum-moleculare (L-M) interneurons in hippocampal slices to examine the temporal aspects of summation of converging perforant path (PP) and mossy fibre (MF) inputs. PP EPSPs were evoked from the s. lacunosum-moleculare in area CA1. MF EPSPs were evoked from the medial extent of the suprapyramidal blade of the dentate gyrus. Summation was strongly supralinear when examining PP EPSP with MF EPSP in a heterosynaptic pair at the 10 ms ISI, and linear to sublinear at longer ISIs. This pattern of nonlinearities suggests that R and L-M interneurons act as coincidence detectors for input from PP and MF. Summation at all ISIs was linear in voltage clamp mode demonstrating that nonlinearities were generated by postsynaptic voltage-dependent conductances. Supralinearity was not detected when the first EPSP in the pair was replaced by a simulated EPSP injected into the soma, suggesting that the conductances underlying the EPSP boosting were located in distal dendrites. Supralinearity was selectively eliminated with either Ni2+ (30 µM), mibefradil (10 µM) or nimodipine (15 µM), but was unaffected by QX-314. This pharmacological profile indicates that supralinearity is due to recruitment of dendritic T-type Ca2+channels by the first subthreshold EPSP in the pair. Results with the hyperpolarization-activated (Ih) channel blocker ZD 7288 (50 µM) revealed that Ih restricted the time course of supralinearity for coincidently summed EPSPs, and promoted linear to sublinear summation for asynchronous EPSPs. We conclude that coincidence detection results from the counterbalanced activation of T-type Ca2+ channels and inactivation of Ih.

(Received 18 February 2008; accepted after revision 3 April 2008; first published online 3 April 2008)
Corresponding author G. Barrionuevo: Department of Neuroscience, A210 Langley Hall, University of Pittsburgh, Pittsburgh, PA, USA. Email: german{at}bs.pitt.edu

E. Calixto and E. J Galván contributed equally to this work. This paper has online supplemental material.






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