Behavioral flexibility is increased by optogenetic inhibition of neurons in the nucleus accumbens shell during specific time segments

Abstract

Behavioral flexibility is vital for survival in an environment of changing contingencies. The nucleus accumbens may play an important role in behavioral flexibility, representing learned stimulus -reward associations in neural activity during response selection and learning from results. To investigate the role of nucleus accumbens neural activity in behavioral flexibility, we used light-activated halorhodopsin to inhibit nucleus accumbens shell neurons during specific time segments of a bar-pressing task requiring a win-stay/lose -shift strategy. We found that optogenetic inhibition during action selection in the time segment preceding a lever press had no effect on performance. However, inhibition occurring in the time segment during feedback of results-whether rewards or nonrewards-reduced the errors that occurred after a change in contingency. Our results demonstrate critical time segments during which nucleus accumbens shell neurons integrate feedback into subsequent responses. Inhibiting nucleus accumbens shell neurons in these time segments, during reinforced performance or after a change in contingencies, increases lose -shift behavior. We propose that the activity of nucleus shell accumbens shell neurons in these time segments plays a key role in integrating knowledge of results into subsequent behavior, as well as in modulating lose -shift behavior when contingencies change.

Optogenetic Activation of Adenosine A2A Receptor Signaling in the Dorsomedial Striatopallidal Neurons Suppresses Goal-Directed Behavior

“…Indeed, modification of instrumental learning by optogenetic manipulation of striatal neurons was only effective in a narrow temporal window [i.e. prior to or concurrent with the onset of cue (Tai et al, 2012), or in the time segment (1.5 seconds) between action selection and outcome (Aquili et al, 2014)], supporting the temporal importance of dopamine, glutamate and neuromodulator signalling in striatum-dependent instrumental learning. Different from rapid neurotransmitter release such as dopamine and glutamate, extracellular adenosine is generated by conversion of ATP to adenosine through a set of ectonucleotidases and by bidirectional nucleotide transporters .…”

Catecholaminergic modulation of indices of cognitive flexibility: A pharmaco-tDCS study

“…Cognitive flexibility, often referred to as behavioural flexibility in animal studies [1], is an essential subdomain of executive function (EF) that facilitates goal-directed behavioural adaptations in response to changing circumstances [2]. The neuronal network subserving cognitive flexibility is thought to include frontostriatal circuits, specifically involving dorsolateral/medial prefrontal cortex (dlPFC/dmPFC), anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), nucleus accumbens (NAC) and the dorsomedial striatum (DMS) [3][4][5][6].…”

WONOEP APPRAISAL: The many facets of epilepsy networks

“…These results indicate that altering neural networks in a way that either terminates seizures as soon as they are detected (eg, RNS), or pushes epileptic networks to self‐organize into a different dynamic pattern that is less likely to generate seizures, is a viable path forward to new therapies. Consistent with the arguments for seizures, direct modification of neural circuits could also positively affect the comorbidities, given that these are also emergent behaviors of an abnormally behaving complex system …”

“…Consistent with the arguments for seizures, direct modification of neural circuits could also positively affect the comorbidities, given that these are also emergent behaviors of an abnormally behaving complex system. [38][39][40] The emphasis of treatment has been on the prevention of seizures. However, conceptualizing epilepsy in a complex systems framework opens the door to treatments that directly target comorbidities.…”