Changes in synaptic efficacy, including long-term potentiation (LTP) and long-term depression (LTD), provide mechanisms for experience-induced plasticity of cortical and subcortical circuits. LTP is readily induced under drastically different experimental conditions (e.g., in vitro and in vivo). However, few studies have compared the effectiveness of different induction protocols to elicit synaptic depression, especially under in vivo conditions. Here, we assessed the effectiveness of four different low frequency stimulation (LFS) protocols, applied to the lateral geniculate nucleus, to induce LTD-like changes of local field postsynaptic potentials (fPSPs) recorded on the surface of the primary visual cortex (V1) of urethane-anesthetized rats. Three LFS protocols (900 pulses at 1 Hz; 1800 pulses at 1 Hz, 1800 pulses at 1 Hz, repeated three times), known to induce LTD in neocortical and hippocampal slice preparations, failed to induce synaptic depression. In contrast, strong low frequency burst stimulation (3 pulses/burst at 20 Hz, 900 bursts repeated at 1 Hz) resulted in significant, but transient ( approximately 20 min) depression of fPSPs in V1. This effect was resistant to systemic treatment with MK 801 (0.5 mg/kg) or local, cortical application of either APV (10 mM) or MCPG (10 mM), indicative of non-essential roles of N-methyl-d-aspartate and metabotropic glutamate receptors. A similar depressant effect was also observed under sodium pentobarbital anesthesia. These experiments emphasize the resistance of the in vivo neocortex to express the long-lasting down-regulation of synaptic strength, observations that require integration into current models and theories regarding the functions of LTD as a homeostatic and experience-dependent plasticity mechanism.
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