Name
Title | ||
|---|---|---|
Separable Actions Of Acetylcholine And Noradrenaline On Neuronal Ensemble Formation In Hippocampal Ca3 Circuits |
Abstract | ||
|---|---|---|
In the hippocampus, episodic memories are thought to be encoded by the formation of ensembles of synaptically coupled CA3 pyramidal cells driven by sparse but powerful mossy fiber inputs from dentate gyrus granule cells. The neuromodulators acetylcholine and noradrenaline are separately proposed as saliency signals that dictate memory encoding but it is not known if they represent distinct signals with separate mechanisms. Here, we show experimentally that acetylcholine, and to a lesser extent noradrenaline, suppress feed-forward inhibition and enhance excitatory-inhibitory ratio in the mossy fiber pathway but CA3 recurrent network properties are only altered by acetylcholine. We explore the implications of these findings on CA3 ensemble formation using a hierarchy of models. In reconstructions of CA3 pyramidal cells, mossy fiber pathway disinhibition facilitates postsynaptic dendritic depolarization known to be required for synaptic plasticity at CA3-CA3 recurrent synapses. We further show in a spiking neural network model of CA3 how acetylcholine-specific network alterations can drive rapid overlapping ensemble formation. Thus, through these distinct sets of mechanisms, acetylcholine and noradrenaline facilitate the formation of neuronal ensembles in CA3 that encode salient episodic memories in the hippocampus but acetylcholine selectively enhances the density of memory storage.</p>Author summaryHow the brain decides which experiences to encode to memory and which to discard is a fundamental question in neuroscience. The neuromodulators acetylcholine and noradrenaline are believed to separately play a central role in determining what is encoded but the mechanisms by which they act are mostly unknown and there have been no direct comparisons made between these two critical neuromodulators. In this study, we investigate the effects of acetylcholine and noradrenaline on a key circuit responsible for the encoding of memories, namely, the dentate gyrus-CA3 microcircuit in the hippocampus. Using slice electrophysiology, we measure the effects of acetylcholine and noradrenaline on key synaptic and cellular nodes within this neuronal network. We then explore the network level implications of these findings on neuronal ensemble formation using a hierarchy of computational models. Based on the observed physiological effects of acetylcholine and noradrenaline, our models predict that acetylcholine facilitates efficient formation of ensembles within CA3 with a high degree of overlap whereas noradrenaline has more limited effects and no impact on the efficiency or overlap of ensemble formation.</p> |
Year | DOI | Venue |
|---|---|---|
2021 | 10.1371/journal.pcbi.1009435 | PLOS COMPUTATIONAL BIOLOGY |
DocType | Volume | Issue |
Journal | 17 | 10 |
ISSN | Citations | PageRank |
1553-734X | 0 | 0.34 |
References | Authors | |
0 | 6 | |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Luke Y Prince | 1 | 0 | 0.34 |
| Travis Bacon | 2 | 0 | 0.34 |
| Rachel Humphries | 3 | 0 | 0.34 |
| Krasimira Tsaneva-Atanasova | 4 | 0 | 3.04 |
| Claudia Clopath | 5 | 3 | 3.76 |
| Jack R Mellor | 6 | 0 | 0.34 |