Cultures of primary neurons or thin brain slices are typicality prepared fr
om immature animals. We introduce a method to prepare hippocampal slice cul
tures from mature rats aged 20-31 days. Mature slice cultures retain hippoc
ampal cytoarchitecture and synaptic connections up to 3 months in vitro. Sp
ontaneous epileptiform activity is rarely observed suggesting long-term ret
ention of normal neuronal excitability and of excitatory and inhibitory syn
aptic networks. Picrotoxin, a GABAergic Cl(-)channel antagonist, induced ch
aracteristic interictal-like bursts that originated in the CA3 region, but
not in the CA1 region. These data suggest that;mature slice cultures displa
yed long-term retention of GABAergic inhibitory synapses that effectively s
uppressed synchronized burst activity via recurrent excitatory synapses of
CA3 pyramidal cells. Mature slice cultures lack the reactive synaptogenesis
, spontaneous epileptiform activity, and short life span that limit the use
of slice cultures isolated from immature rats. Mature slice cultures are a
nticipated to be a useful addition for the in vitro study of normal and pat
hological hippocampal function. (C) 2000 Elsevier Science B.V. All rights r
eserved.