Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus-timing dependent plasticity in fusiform cells of the dorsal cochlear nucleus.

Cholinergic modulation contributes to adaptive sensory processing by controlling spontaneous and stimulus-evoked neural activity and long term synaptic plasticity. In the dorsal cochlear nucleus, in vitro activation of muscarinic acetylcholine receptors (mAChRs) alters the spontaneous activity of DCN neurons and interacts with NMDA (N-methyl-D-aspartate) and endocannabinoid receptors to modulate the plasticity of parallel fiber synapses onto fusiform cells by converting Hebbian LTP to anti-Hebbian LTD. Because noise exposure and tinnitus are known to increase spontaneous activity in fusiform cells as well as alter stimulus-timing dependent plasticity (StTDP), it is important to understand the contribution of mAChRs to in vivo spontaneous activity and plasticity in fusiform cells. Here, we block mAChRs actions by infusing atropine, a mAChR antagonist, into the DCN fusiform cell layer in normal hearing guinea pigs. Atropine delivery leads to decreased spontaneous firing rates and increased synchronization of fusiform cell spiking activity. Consistent with StTDP alterations observed in tinnitus animals, atropine infusion induces a dominant pattern of inversion of StTDP mean population learning rule from a Hebbian to an anti-Hebbian profile. Units preserving their initial Hebbian learning rules shift towards more excitatory changes in StTDP while units with initial suppressive learning rules transition towards a Hebbian profile. Together, these results implicate muscarinic cholinergic modulation as a factor in controlling in vivo fusiform cell baseline activity and plasticity suggesting a central role in the maladaptive plasticity associated with tinnitus pathology.

Copyright © 2016, Journal of Neurophysiology.