In the intermediate and medial hyperstriatum ventrale (IMHV), a telencephalic region essentially involved in the initial processes of early learning tasks in poultry chicks, induction of an immediate early gene c-fos correlates significantly with the degree of learning (K.V. Anokhin, R. Mileusnic, I.Y. Shamakina, S.P.R. Rose, Effects of early experience on c-fos gene expression in the chick forebrain, Brain Res. 544 (1991) 101-107; B.J. McCabe, G. Horn, Learning-related changes in Fos-like immunoreactivity in the chick forebrain after imprinting, Proc. Natl. Acad. Sci. USA 91 (1994) 11417-11421). In slices of IMHV in vitro, on the other hand, tetanic stimulation at a low frequency induces a potentiation of synaptic responses (P.M. Bradley, B.D. Burns, A.C. Webb, Potentiation of synaptic responses in slices from the chick forebrain, Proc. R. Soc. Lond. B. 243 (1991) 19-24; T. Matsushima, K. Aoki, Potentiation and depotentiation of DNQX-sensitive fast excitatory synaptic transmission in telencephalon of the quail chick, Neurosci. Lett. 185 (1995) 179-182). In this study, we have examined a possible causal link between these two forms of activity-dependent processes, c-fos expression and synaptic potentiation. C-fos was visualized immunohistochemically using antibody raised against the Fos-protein, and potentiation was evaluated on the basis of field potential responses to local electrical stimulation. Tetanic stimulation (5 Hz x 300 pulses) was required for potentiation, but not for c-fos expression. Conversely, a negative correlation appeared between them, and slices with relatively high density of Fos-like immunoreactive cells around the stimulation site failed to show potentiation. Furthermore, drugs similarly effective in blocking potentiation (such as AP5 (NMDA receptor antagonist) and bicuculline (GABA(A) receptor antagonist)) had different effects on the c-fos induction. While AP5 had minor, if any, effects on c-fos expression, bicuculline enhanced it selectively around the site of stimulation. Our results suggest that these two processes are basically distinct, and could represent different aspects in the formation of memory traces in IMHV.