Modulation of long-term synaptic depression in visual cortex by acetylcholine and norepinephrine

In a slice preparation of rat visual cortex, we discovered that paired-puls e stimulation (PPS) elicits a form of homosynaptic long-term depression (LT D) in the superficial layers when carbachol (CCh) or norepinephrine (NE) is applied concurrently. PPS by itself, or CCh and NE in the absence of synap tic stimulation, produced no lasting change. The LTD induced by PPS in the presence of NE or CCh is of comparable magnitude with that obtained with pr olonged low-frequency stimulation (LFS) but requires far fewer stimulation pulses (40 vs 900). The cholinergic facilitation of LTD was blocked by atro pine and pirenzepine, suggesting involvement of M-1 receptors. The noradren ergic facilitation of LTD was blocked by urapidil and was mimicked by metho xamine, suggesting involvement of alpha 1 receptors. beta receptor agonists and antagonists were without effect. Induction of LTD by PPS was inhibited by NMDA receptor blockers (completely in the case of NE; partially in the case of CCh), suggesting that one action of the modulators is to control th e gain of NMDA receptor-dependent homosynaptic LTD in visual cortex. We pro pose that this is a mechanism by which cholinergic and noradrenergic inputs to the neocortex modulate naturally occurring receptive field plasticity.