Altering gain of the infralimbic-to-accumbens shell circuit alters economically dissociable decision-making algorithms

Abstract

<p id="d2058478e216">Synaptic remodeling in the infralimbic-to-accumbens shell (IL–NAcSh) circuit is linked to addiction relapse susceptibility; however, how these changes interact with decision-making computations remains unclear. We develop a neurophysiological assay to measure the strength of a specific circuit at the ensemble level. We then use that assay in combination with a neuroeconomic task to provide causal evidence that synaptic strength of the IL–NAcSh mediates distinct aspects of decision-making information processing. We find that individual differences in IL–NAcSh strength mediate reevaluations behaviorally resolvable from parallel, co-occurring deliberative valuations. An important implication of our work is that acutely delivered circuit-specific plasticity manipulations can produce long-lasting computation-specific effects on certain kinds of choices and can potentially serve as a therapeutic neuromodulation intervention. </p><p class="first" id="d2058478e219">The nucleus accumbens shell (NAcSh) is involved in reward valuation. Excitatory projections from infralimbic cortex (IL) to NAcSh undergo synaptic remodeling in rodent models of addiction and enable the extinction of disadvantageous behaviors. However, how the strength of synaptic transmission of the IL–NAcSh circuit affects decision-making information processing and reward valuation remains unknown, particularly because these processes can conflict within a given trial and particularly given recent data suggesting that decisions arise from separable information-processing algorithms. The approach of many neuromodulation studies is to disrupt information flow during on-going behaviors; however, this limits the interpretation of endogenous encoding of computational processes. Furthermore, many studies are limited by the use of simple behavioral tests of value which are unable to dissociate neurally distinct decision-making algorithms. We optogenetically altered the strength of synaptic transmission between glutamatergic IL–NAcSh projections in mice trained on a neuroeconomic task capable of separating multiple valuation processes. We found that induction of long-term depression in these synapses produced lasting changes in foraging processes without disrupting deliberative processes. Mice displayed inflated reevaluations to stay when deciding whether to abandon continued reward-seeking investments but displayed no changes during initial commitment decisions. We also developed an ensemble-level measure of circuit-specific plasticity that revealed individual differences in foraging valuation tendencies. Our results demonstrate that alterations in projection-specific synaptic strength between the IL and the NAcSh are capable of augmenting self-control economic valuations within a particular decision-making modality and suggest that the valuation mechanisms for these multiple decision-making modalities arise from different circuits. </p>