Long-term depression (LTD) is a widely studied form of activity-dependent synaptic plasticity, typically induced by prolonged low-frequency stimulation (LFS). LFS is highly effective in eliciting LTD in vitro, but several studies have failed to induce LTD using LFS in vivo, for reasons that remain unclear. The main objective of this thesis was to assess whether different levels of ongoing background activity in the primary visual cortex (V1) alter the effectiveness of LFS to induce LTD under in vivo conditions, using urethane anesthetized rats. LFS applied to the lateral geniculate nucleus resulted in LTD of field postsynaptic potentials (fPSPs) recorded in the primary visual cortex (V1). Pairing LFS with stimulation of the brainstem (pedunculopontine) reticular formation resulted in the appearance of faster, more complex activity in V1 and prevented LTD induction. Reticular stimulation alone (without LFS) had no effect on cortical fPSPs. Application of scopolamine and mecamylamine did not restore LTD or prevent the complex oscillatory activity seen in V1. These results show that excitation of the brainstem activating system blocks the induction of LTD in V1. Thus, higher levels of neural activity may inhibit depression at cortical synapses, a hypothesis that could explain discrepancies regarding LTD induction in previous in vivo and in vitro work.