Abstract
Hilar mossy cells (HMCs) in the hippocampus receive glutamatergic input from dentate granule cells (DGCs) via mossy fibers (MFs) and back-projections from CA3 pyramidal neuron collateral axons. Many fundamental features of these excitatory synapses have not been characterized in detail despite their potential relevance to hippocampal cognitive processing and epilepsy-induced adaptations in circuit excitability. In this study, we compared preand postsynaptic parameters between MF and CA3 inputs to HMCs in young and adult mice of either sex and determined the relative contributions of the respective excitatory inputs during in vitro and in vivo models of hippocampal hyperexcitability. The two types of excitatory synapses both exhibited a modest degree of short-term plasticity, with MF inputs to HMCs exhibiting lower paired-pulse (PP) and frequency facilitation than was described previously for MF–CA3 pyramidal cell synapses. MF–HMC synapses exhibited unitary excitatory synaptic currents (EPSCs) of larger amplitude, contained postsynaptic kainate receptors, and had a lower NMDA/AMPA receptor ratio compared to CA3–HMC synapses. Pharmacological induction of hippocampal hyperexcitability in vitro transformed the abundant but relatively weak CA3–HMC connections to very large amplitude spontaneous bursts of compound EPSCs (cEPSCs) in young mice (∽P20) and, to a lesser degree, in adult mice (∽P70). CA3–HMC cEPSCs were also observed in slices prepared from mice with spontaneous seizures several weeks after intrahippocampal kainate injection. Strong excitation of HMCs during synchronous CA3 activity represents an avenue of significant excitatory network generation back to DGCs and might be important in generating epileptic networks.
| Original language | English (US) |
|---|---|
| Article number | e0364-17.2017 |
| Journal | eNeuro |
| Volume | 4 |
| Issue number | 6 |
| DOIs | |
| State | Published - Nov 1 2017 |
Funding
Received October 23, 2017; accepted November 10, 2017; First published November 22, 2017. The authors declare no competing financial interests. Author contributions: T.P.H., W.P.N., K.M.F., D.M.C., and G.T.S. designed research; T.P.H., W.P.N., K.M.F., and T.I. performed research; T.P.H., W.P.N., K.M.F., and T.I. analyzed data; T.P.H., W.P.N., and G.T.S. wrote the paper. This work was supported by National Institute of Neurological Disorders and Stroke Grants R21 NS090040 (to G.T.S.) and R01NS059934 (to D.M.C.) and by a Nippon Medical School Grant-in-Aid for Overseas Training (2017) grant funded by the Operating Costs Subsidies for Private Universities (T.I.). *T.P.H. and W.P.N. contributed equally to this work. Correspondence should be addressed to Geoffrey T. Swanson, Department of Pharmacology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60611, E-mail: [email protected]. DOI:http://dx.doi.org/10.1523/ENEURO.0364-17.2017 Copyright © 2017 Hedrick et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords
- Aging
- CA3
- Hilus
- Mossy cell
- Seizure
ASJC Scopus subject areas
- General Neuroscience