TY - JOUR
T1 - Theta-gamma coupling emerges from spatially heterogeneous cholinergic neuromodulation
AU - Yang, Yihao
AU - Gritton, Howard
AU - Sarter, Martin
AU - Aton, Sara J.
AU - Booth, Victoria
AU - Zochowski, Michal
N1 - Publisher Copyright:
© 2021 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/7
Y1 - 2021/7
N2 - Theta and gamma rhythms and their cross-frequency coupling play critical roles in perception, attention, learning, and memory. Available data suggest that forebrain acetylcholine (ACh) signaling promotes theta-gamma coupling, although the mechanism has not been identified. Recent evidence suggests that cholinergic signaling is both temporally and spatially constrained, in contrast to the traditional notion of slow, spatially homogeneous, and diffuse neuromodulation. Here, we find that spatially constrained cholinergic stimulation can generate theta-modulated gamma rhythms. Using biophysically-based excitatory-inhibitory (E-I) neural network models, we simulate the effects of ACh on neural excitability by varying the conductance of a muscarinic receptor-regulated K+ current. In E-I networks with local excitatory connectivity and global inhibitory connectivity, we demonstrate that thetagamma- coupled firing patterns emerge in ACh modulated network regions. Stable gammamodulated firing arises within regions with high ACh signaling, while theta or mixed thetagamma activity occurs at the peripheries of these regions. High gamma activity also alternates between different high-ACh regions, at theta frequency. Our results are the first to indicate a causal role for spatially heterogenous ACh signaling in the emergence of localized theta-gamma rhythmicity. Our findings also provide novel insights into mechanisms by which ACh signaling supports the brain region-specific attentional processing of sensory information.
AB - Theta and gamma rhythms and their cross-frequency coupling play critical roles in perception, attention, learning, and memory. Available data suggest that forebrain acetylcholine (ACh) signaling promotes theta-gamma coupling, although the mechanism has not been identified. Recent evidence suggests that cholinergic signaling is both temporally and spatially constrained, in contrast to the traditional notion of slow, spatially homogeneous, and diffuse neuromodulation. Here, we find that spatially constrained cholinergic stimulation can generate theta-modulated gamma rhythms. Using biophysically-based excitatory-inhibitory (E-I) neural network models, we simulate the effects of ACh on neural excitability by varying the conductance of a muscarinic receptor-regulated K+ current. In E-I networks with local excitatory connectivity and global inhibitory connectivity, we demonstrate that thetagamma- coupled firing patterns emerge in ACh modulated network regions. Stable gammamodulated firing arises within regions with high ACh signaling, while theta or mixed thetagamma activity occurs at the peripheries of these regions. High gamma activity also alternates between different high-ACh regions, at theta frequency. Our results are the first to indicate a causal role for spatially heterogenous ACh signaling in the emergence of localized theta-gamma rhythmicity. Our findings also provide novel insights into mechanisms by which ACh signaling supports the brain region-specific attentional processing of sensory information.
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U2 - 10.1371/journal.pcbi.1009235
DO - 10.1371/journal.pcbi.1009235
M3 - Article
C2 - 34329297
AN - SCOPUS:85111749900
SN - 1553-734X
VL - 17
JO - PLoS computational biology
JF - PLoS computational biology
IS - 7
M1 - e1009235
ER -