Cooperation between cholinergic and glutamatergic receptors are essential to induce BDNF‐dependent long‐lasting memory storage

Abstract

The induction of long-lasting memory storage depends on the behavioral state of humans and animals. This behavioral state is mediated by neuromodulatory systems, like the cholinergic-septum-hippocampal circuit. Cholinergic neurotransmission is known to affect short-term activity-dependent plasticity in various brain areas, including the hippocampus. We could show here that a chemical late-long-term potentiation (LTP) could be induced in the basal dendrites by the coapplication of the cholinergic receptor agonist, carbachol, and the phosphodiesterase type 4 (PDE4)-inhibitor, rolipram at a concentration that by itself has no effect on basal synaptic transmission. This chemical late-LTP was similar to electrical late-LTP in that it is dependent on protein synthesis, cAMP, and NMDA-receptor activation. Occlusion experiments demonstrated that saturation of three tetanus (TET) late-LTP occluded carbachol-rolipram-LTP, indicating that they share similar properties. This cholinergic modulation of LTP in the basal dendrites was mediated by both muscarinic and nicotinic receptors. Carbachol also reinforced an early form of LTP into a long-lasting LTP. Most interestingly, these two forms of LTP could participate in the functional plasticity processes like synaptic tagging and capture (STC). In addition, we studied whether a cooperation between cholinergic and glutamatergic receptors is essential to induce functional synaptic-plasticity. Indeed, we could show that coactivation of acetylcholine/PDE4 inhibition must coincide with the release of glutamate to induce a long-lasting plasticity, showing a functional convergence of the two neuromodulatory systems. Moreover, we could also show that both chemical late-LTP and carbachol-reinforced early-LTP-induced STC processes are mediated by the neurotrophin BDNF.