Contributions of the amygdala and medial prefrontal cortex to incentive cue responding

doi:10.1016/j.neuroscience.2008.06.037

Neuroscience

Volume 155, Issue 3, 26 August 2008, Pages 573-584

https://doi.org/10.1016/j.neuroscience.2008.06.037 Get rights and content

Abstract

Reward-seeking behavior is controlled by neuronal circuits that include the basolateral nucleus of amygdala (BLA), medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and ventral tegmental area. Using a discriminative stimulus (DS) task in which an intermittently presented cue (DS) directs rats to make an operant response for sucrose, we previously demonstrated that dopamine receptor antagonism in the NAc reduced reinforced cue responding, whereas general inactivation of the NAc increased behavioral responding in the absence of the cue. Because they send major glutamatergic projections to the NAc, the BLA and mPFC may also contribute to reward-seeking behaviors modulated by the NAc. In this study we compare the effects of BLA and mPFC inactivation on rats’ performance of a DS task. BLA inactivation by combined GABA_A and GABA_B agonists impaired cue responding with minimal effects on operant behavior in the absence of cues. Dorsal medial prefrontal cortex (dmPFC) inactivation also inhibited cue-evoked reward-seeking. In contrast, ventral medial prefrontal cortex (vmPFC) inactivation disinhibited responding to unrewarded cues with less influence on reinforced cue responding. These findings demonstrate that the BLA and dmPFC facilitate cue-evoked reward-seeking, whereas, in the same task the vmPFC exerts inhibitory control over unrewarded behaviors.

Section snippets

Subjects

Thirty-two male Long-Evans rats (∼350 g on arrival) were individually housed in a colony room maintained on a 12-h light/dark cycle. All experiments occurred during the light portion of the cycle. After receipt, rats were allowed at least 1 week of ad libitum food and water, followed by 1 week of restricted food and water before training. Animals were fed 13 g of BioServ (Frenchtown, NJ, USA) formula F-173 pellets (1 g each) and 30 ml of water per day for the duration of the experiments.

The role of the BLA in reward-seeking behaviors

Inactivating the BLA with GABA_A and GABA_B agonists (M/B) impaired cue responding behavior (Fig. 1). M/B induced a dose-dependent decrease in DS response ratio (F_3,21=22.77, P<0.0001; Fig. 1A). Responding to the NS was also reduced by BLA inactivation (F_3,21=12.31, P<0.0001; Fig. 1C). Although the DS response latency tended to increase following BLA inactivation, there was no significant difference among groups (F_3,21=1.58, P=0.23; Fig. 1B). The rate of uncued responding on the active lever was

Discussion

To obtain reward in the DS task, animals must perform an operant response during DS presentation. During the long (30 s) intervals between cue presentations, and during NS presentation, reward is not available. Previously, we showed that dopamine acting in the NAc is required for animals to respond during the DS (Yun et al 2004a, Yun et al 2004b). However, NAc neurons also inhibit behaviors that animals have learned to suppress in the context of a reward seeking task, as demonstrated by an

Acknowledgments

Funding: State of California/University of California, San Francisco (Alcohol and Substance Abuse Research Program to H.L.F.); National Institutes of Health (DA019473 to S.M.N.); Wheeler Center for the Neurobiology of Addiction. The authors are grateful to Dr. V. Kharazia for histology work.

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Indeed, previous studies have shown an intact BLA is needed to access the value of the learned cue in order to appropriately update it when the outcome is changed and alter behavioral responding (as reviewed in (Wassum & Izquierdo, 2015)). The BLA encodes the value of the cues during learning (Cole et al., 2013; Esber & Holland, 2014; Parkes & Balleine, 2013; Piette et al., 2012; Schoenbaum et al., 1999; Tye & Janak, 2007; Uwano, Nishijo, Ono, & Tamura, 1995) and is involved in appetitive cue discrimination (Ambroggi, Ishikawa, Fields, & Nicola, 2008; Ishikawa et al., 2008) and reversal learning (Churchwell, Morris, Heurtelou, & Kesner, 2009). However, several studies have shown the BLA may not be critical for initial acquisition of cue value learning (Balleine, Killcross, & Dickinson, 2003; Corbit & Balleine, 2005; Hatfield et al., 1996; Holland, Petrovich, & Gallagher, 2002; Parkinson, Robbins, & Everitt, 2000), but it is critical to encode and assess the representation of the learned associations to alter subsequent behavioral motivation and learning (Blundell et al., 2001; Corbit & Balleine, 2005; Coutureau, Marchand, & Di Scala, 2009; Everitt et al., 2003; Galarce, McDannald, & Holland, 2010; Hatfield et al., 1996; Holland et al., 2002; Holland & Petrovich, 2005; Johnson, Gallagher, & Holland, 2009; Ostlund & Balleine, 2008; Petrovich, 2013; Setlow et al., 2002; Tye & Janak, 2007; Wassum & Izquierdo, 2015; Hoang & Sharpe, 2021; Fisher et al., 2020).
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Interestingly, disconnecting the PL-NAcC circuit does not impact cued reinstatement of sucrose-seeking, bringing into question the generalizability of the proposed role of the PL-NAcC in initiating drug-seeking to natural reward-seeking. However, in a study by Ishikawa et al. (2008a,b), pharmacological inactivation of the PL was found to abolish firing in the NAcC during sucrose-seeking under the control of a discriminative stimulus. Furthermore, optogenetic activation of PL inputs to the NAc has been shown to enhance acquisition of conditioned sucrose-seeking while inhibition reduces conditioned sucrose-seeking (Otis et al., 2017).
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Behavioural neuroscienceContributions of the amygdala and medial prefrontal cortex to incentive cue responding

Abstract

Section snippets

Subjects

The role of the BLA in reward-seeking behaviors

Discussion

Acknowledgments

Incentive cue encoding in the nucleus accumbens depends on basolateral amygdala inputs

Neuron

Parallel incentive processing: an integrated view of amygdala function

Trends Neurosci

The amygdala and reward

Nat Rev Neurosci

Lesions of the basolateral amygdala disrupt selective aspects of reinforcer representation in rats

J Neurosci

Dopaminergic modulation of prefrontal cortical input to nucleus accumbens neurons in vivo

J Neurosci

The patterns of afferent innervation of the core and shell in the “accumbens” part of the rat ventral striatum: immunohistochemical detection of retrogradely transported fluoro-gold

J Comp Neurol

Dopamine receptor subtypes selectively modulate excitatory afferents from the hippocampus and amygdala to rat nucleus accumbens neurons

Neuropsychopharmacology

Nucleus accumbens neurons encode Pavlovian approach behaviors: evidence from an autoshaping paradigm

Eur J Neurosci

Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement

Annu Rev Neurosci

Basolateral amygdala stimulation evokes glutamate receptor-dependent dopamine efflux in the nucleus accumbens of the anaesthetized rat

Eur J Neurosci

Persistent cue-evoked activity of accumbens neurons after prolonged abstinence from self-administered cocaine

J Neurosci

Working memory, response selection, and effortful processing in rats with medial prefrontal lesions

Behav Neurosci

Neurotoxic lesions of basolateral, but not central, amygdala interfere with pavlovian second-order conditioning and reinforcer devaluation effects

J Neurosci

The prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics

Neurosci Biobehav Rev

Dopamine excites nucleus accumbens neurons through the differential modulation of glutamate and GABA release

J Neurosci

Dopamine gating of glutamatergic sensorimotor and incentive motivational input signals to the striatum

Behav Brain Res

Contrasting contributions of the prefrontal cortex and amygdala to cue-evoked reward seeking behavior

Soc Neurosci Abstr.

Dorsomedial prefrontal cortex contribution to behavioral and nucleus accumbens neuronal responses to incentive cues

J Neurosci

Selective responsiveness of medial prefrontal cortex neurons to the meaningful stimulus with a low probability of occurrence in rats

Brain Res

Input from the amygdala to the rat nucleus accumbens: its relationship with tyrosine hydroxylase immunoreactivity and identified neurons

Neuroscience

Dopaminergic modulation of glutamate-induced excitation of neurons in the neostriatum and nucleus accumbens of awake, unrestrained rats

J Neurophysiol

Responses of monkey dopamine neurons during learning of behavioral reactions

J Neurophysiol

The organization of the projection from the cerebral cortex to the striatum in the rat

Neuroscience

From motivation to action: functional interface between the limbic system and the motor system

Prog Neurobiol

Rat amygdaloid neuron responses during auditory discrimination

Neuroscience

Reversible inactivation of rat medial prefrontal cortex impair the ability to wait for a stimulus

Neuroscience

The nucleus accumbens as part of a basal ganglia action selection circuit

Psychopharmacology

Behavioural neuroscience
Contributions of the amygdala and medial prefrontal cortex to incentive cue responding