Role of the noradrenergic system in synaptic plasticity in the hippocampus

The cortical noradrenergic (NAergic) system, which originates from the locus coeruleus (LC) located in the pons, plays an important role in cortical plasticity and many other brain functions. In rats in which the NAergic system has been eliminated by 6-hydroxydopamine during the neonatal period, induction of long-term potentiation (LTP) at CA1 synapses in the hippocampus is impaired, whereas induction of long-term depression is unaffected. Bath application of norepinephrine, a β-adrenergic receptor agonist, or activators of effector molecules downstream of the β-adrenergic receptor restores LTP. Similarly, activation of β-adrenergic receptors enhances associative LTP induced by paired stimuli to two independent synaptic inputs on the same postsynaptic neuron. The time window within which LTP can be induced by paired stimuli is increased by β-adrenergic receptor activation, but the magnitude of LTP is not affected. The signaling molecules involved in enhancement of the homosynaptic and associative LTP following β-adrenergic receptor activation are the same and include protein kinase A and mitogen-activated protein kinases. These experimental results suggest that a simultaneous increase in the activity of LC neurons during induction protocols may have a permissive role in the induction of homosynaptic and associative LTP in the hippocampus.