» Articles » PMID: 38033788

Acetylcholine Facilitates Localized Synaptic Potentiation and Location Specific Feature Binding

Overview
Date 2023 Nov 30
PMID 38033788
Authors
Affiliations
Soon will be listed here.
Abstract

Forebrain acetylcholine (ACh) signaling has been shown to drive attention and learning. Recent experimental evidence of spatially and temporally constrained cholinergic signaling has sparked interest to investigate how it facilitates stimulus-induced learning. We use biophysical excitatory-inhibitory (E-I) multi-module neural network models to show that external stimuli and ACh signaling can mediate spatially constrained synaptic potentiation patterns. The effects of ACh on neural excitability are simulated by varying the conductance of a muscarinic receptor-regulated hyperpolarizing slow K+ current (m-current). Each network module consists of an E-I network with local excitatory connectivity and global inhibitory connectivity. The modules are interconnected with plastic excitatory synaptic connections, that change via a spike-timing-dependent plasticity (STDP) rule. Our results indicate that spatially constrained ACh release influences the information flow represented by network dynamics resulting in selective reorganization of inter-module interactions. Moreover the information flow depends on the level of synchrony in the network. For highly synchronous networks, the more excitable module leads firing in the less excitable one resulting in strengthening of the outgoing connections from the former and weakening of its incoming synapses. For networks with more noisy firing patterns, activity in high ACh regions is prone to induce feedback firing of synchronous volleys and thus strengthening of the incoming synapses to the more excitable region and weakening of outgoing synapses. Overall, these results suggest that spatially and directionally specific plasticity patterns, as are presumed necessary for feature binding, can be mediated by spatially constrained ACh release.

References
1.
Ernst U, Pawelzik K, Tsodyks M . Intracortical origin of visual maps. Nat Neurosci. 2001; 4(4):431-6. DOI: 10.1038/86089. View

2.
Wittenberg G, Wang S . Malleability of spike-timing-dependent plasticity at the CA3-CA1 synapse. J Neurosci. 2006; 26(24):6610-7. PMC: 6674029. DOI: 10.1523/JNEUROSCI.5388-05.2006. View

3.
Mitsushima D, Sano A, Takahashi T . A cholinergic trigger drives learning-induced plasticity at hippocampal synapses. Nat Commun. 2013; 4:2760. PMC: 3831287. DOI: 10.1038/ncomms3760. View

4.
Nelson S, Sjostrom P, Turrigiano G . Rate and timing in cortical synaptic plasticity. Philos Trans R Soc Lond B Biol Sci. 2003; 357(1428):1851-7. PMC: 1693081. DOI: 10.1098/rstb.2002.1162. View

5.
Stiefel K, Gutkin B, Sejnowski T . The effects of cholinergic neuromodulation on neuronal phase-response curves of modeled cortical neurons. J Comput Neurosci. 2008; 26(2):289-301. PMC: 2857973. DOI: 10.1007/s10827-008-0111-9. View