Metabotropic Glutamate Receptor Mediated Long-term Depression in Developing Hippocampus
Section snippets
MATERIALS AND METHODS
Hippocampal slices from Sprague-Dawley rats (8–33 days postnatal age) were prepared as follows: animals were anesthetized with isoflorane (age >12 days only), decapitated and the brains were removed and placed in chilled artificial cerebrospinal fluid (ACSF) gassed with 95% O2/5% CO2 and containing (in mM): NaCl 124, KCl 3, MgSO4 1.3, NaHPO4 1.25, CaCl2 2.4, NaHCO3 24 and d-glucose 10 (pH 7.4). Slices (350–400 μm thick) were cut on a vertical tissue chopper (Stoelting), incubated at room
Developmental changes in mGluR-activated long-term plasticity
ACPD (10 μM) was bath-applied for 20 min to slices at four developmental stages: 8–12 days, 15–17 days, 21–24 days and 28–33 days. As shown in Fig. 1Fig. 2Fig. 3, the bath application of ACPD induced both acute and long-term changes in synaptic transmission, and the direction of plastic change was highly age-dependent. As is summarized for all experiments in Fig. 1(A) (PS amplitude, n = 34) and Fig. 1(C) (EPSP slope, n = 53), the long-term plastic change (measured 30–40 min following the
DISCUSSION
The major result of our studies is that the bath application of 10 μM ACPD, an mGluR agonist, induces both acute and long-lasting depression of neurotransmission at the SC-CA1 synapse in immature animals (8–12 days postnatal age). This ACPD-induced synaptic depression is consistently biphasic in appearance, characterized by an acute decrease to ∼ 50–60% of baseline EPSP slope in the presence of agonist and partial reversal to ∼ 75–80% of baseline EPSP slope after washout. The transient
Acknowledgements
This work was supported in part by K08-NS01498 (NINDS) to B.L.T., by an American Epilepsy Society Research Grant (Milken Family Medical Foundation) to B.L.T. and by generous gifts from Open Hearts for Retarded Children, the Ida and Arie Crown Memorial Fund and Mrs Rudy L. Ruggles. We thank Ms Teng Ji for participation in some of these experiments. This work fulfills in part the requirement for a Ph.D. degree for Linda S. Overstreet.
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Present affiliation: Neurotherapeutics, Chicago, Illinois, U.S.A.