Presynaptic KAR activity can be up- or down-regulated in response to different frequencies of neuronal activity at immature glutamatergic synapses. Long-term depression (LTD) in the area CA1 of neonatal rodent hippocampus is associated with an up-regulation of tonic inhibitory KAR activity, which contributs to synaptic depression and causes a pronounced increase in short-term facilitation of transmission. This increased KAR function was mediated by high-affinity receptors and required activation of NMDA receptors, nitric oxide synthetase (NOS) and postsynaptic calcium signalling. In contrast, KAR activity was irreversibly down-regulated in response to induction of long-term potentiation (LTP) in a manner that depended on activation of the TrkB—receptor of BDNF. Both tonic KAR activity and its plasticity were restricted to early stages of synapse development and were lost in parallel with maturation of the network, due to ongoing BDNF-TrkB signalling.
These data show that presynaptic KARs are targets for activity-dependent modulation via diffusible messengers NO and BDNF, which enhance and depress tonic KAR activity at immature synapses, respectively. The plasticity of presynaptic KARs in the developing network contributes to LTD and LTP in a developmentally restricted period of synapse maturation. Unlike the purely postsynaptic changes in synapse strength, the KAR dependent changes in transmitter release allows nascent synapses to shape their dynamic response to incoming activity. In particular, up-regulation of KAR function after LTD allows the synapse to preferentially pass high-frequency afferent activity. This can provide a potential rescue from synapse elimination by uncorrelated activity and also increase the computational dynamics of the developing CA3-CA1 circuitry.
Clarke VR, Molchanova SM, Hirvonen T, Taira T, Lauri SE. (2014) J Neurosci. 34(50):16902-16.
Sallert M, Rantamäki T, Vesikansa A, Anthoni H, Harju K, Yli-Kauhaluoma J, Taira T, Castren E, Lauri SE. (2009) J Neurosci 29(36):11294-303.