Degenerate neural circuits perform the same function despite being structurally different. However, it is unclear whether neural circuits with interacting neuromodulator sources can themselves degenerate while maintaining the same neuromodulatory function. Here, we address this by computationally modeling the neural circuits of neuromodulators serotonin and dopamine, local glutamatergic and GABAergic interneurons, and their possible interactions, under reward/punishment-based conditioning tasks. The neural modeling is constrained by relevant experimental studies of the VTA or DRN system using, e.g., electrophysiology, optogenetics, and voltammetry. We first show that a single parsimonious, sparsely connected neural circuit model can recapitulate several separate experimental findings that indicated diverse, heterogeneous, distributed, and mixed DRNVTA neuronal signaling in reward and punishment tasks. The inability of this model to recapitulate all observed neuronal signaling suggests potentially multiple circuits acting in parallel. Then using computational simulations and dynamical systems analysis, we demonstrate that several different stable circuit architectures can produce the same observed network activity profile, hence demonstrating degeneracy. Due to the extensive D2-mediated connections in the investigated circuits, we simulate the D2 receptor agonist by increasing the connection strengths emanating from the VTA DA neurons. We found that the simulated D2 agonist can distinguish among sub-groups of the degenerate neural circuits based on substantial deviations in specific neural populations’ activities in reward and punishment conditions. This forms a testable model prediction using pharmacological means. Overall, this theoretical work suggests the plausibility of degeneracy within neuromodulator circuitry and has important implications for the stable and robust maintenance of neuromodulatory functions.
Bibliographical noteFunding Information:
CB was supported by the Ulster University Research Challenge Fund. AJ, TS, and KW-L were supported by the BBSRC (BB/P003427/1). KW-L and D-HW were jointly supported by the Royal Society—NSFC International Exchanges. KW-L was further supported by COST Action Open Multiscale Systems Medicine (Open Multi Med) supported by COST (European Cooperation in Science and Technology), and Northern Ireland Functional Brain Mapping Facility (1303/101154803) funded by the Invest NI and the University of Ulster. D-HW received further support from NSFC under grants 32171094 and 31511130066.
Copyright © 2023 Behera, Joshi, Wang, Sharp and Wong-Lin.
- computational modelling
- reward and punishment
- computational modeling