Blocking NK1 receptors disrupts the sequential and temporal organization of chain grooming in rats

Favila, Natalia; Gurney, Kevin; Overton, Paul G.

doi:10.1016/j.neuropharm.2021.108716

Cited by 3 publications

(3 citation statements)

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“…Although neuropeptides have been neglected in the study of sequence learning, recent findings have implicated SP in action sequencing ( Buxton et al, 2017 ; Favila et al, 2021 ). Our results suggest that administering an NK1 receptor antagonist led to a faster disintegration of a well-learned sequence.…”

Section: Discussionmentioning

confidence: 99%

“…The waiting time between the injection and the experiment was 20 min. Both the dose and the waiting time were selected based on a previous study in which we found effects on innate sequential patterns with such dose and waiting time ( Favila et al, 2021 ). The time the rats spent in the operant box after the injection depended on how long they took to obtain 50 reinforcers, with a maximum of 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…Although these results clearly suggest that impairment of NK1 receptors leads to disrupted action selection in an unordered serial task, few studies have focused on the role of SP in ordered action sequences that need to be integrated as a unit. Nevertheless, it has been reported that NK1 receptor antagonism leads to the inhibition of stereotypical behaviors ( Duffy et al, 2002 ) and to disruptions inside the highly fixed and ordered grooming chain displayed by rats ( Favila et al, 2021 ). Therefore, we hypothesized that SP could play a significant role in the changes in cortico-striatal synapses and dopamine that have been proposed as fundamental for learning and performing action sequences ( Jin and Costa, 2015 ; Nakamura et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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The NK1 antagonist L-733,060 facilitates sequence learning

2023

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Background: Although several brain regions and electrophysiological patterns have been related to sequence learning, less attention has been paid to the role that different neuromodulators play. Aims: Here we sought to investigate the role of substance P (SP) in sequence learning in an operant conditioning preparation, supported by a reinforcement learning model. Methods: Two experiments were performed to test the effects of an NK1 receptor (at which SP primarily acts) antagonist on learning and performing action sequences. In experiment 1, rats were trained to perform an action sequence until stable performance was achieved, and then, in phase 2, they were switched to perform the reverse sequence. In experiment 2, rats were trained to perform an action sequence, and in phase 2, they continued to do the same sequence. In both experiments in the first 3 days of phase 2, rats were injected with an NK1 receptor antagonist (L-733,060, i.p.) or with vehicle. Additionally, we developed a reinforcement learning model which allowed the in silico replication of our experimental tasks. Results: We found that administering an NK1 receptor antagonist weakened the stable retention of a well-learned sequence, allowing the faster acquisition of a new sequence, without impairing the continued performance of a crystallized sequence. Using our reinforcement learning model, we suggest that SP could be acting through the state value learning rate, modulating the effects of the reward prediction error. Conclusions: Our results suggest that SP could be involved in the consolidation of a sequence representation through a modulatory effect on the reward prediction error.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The NK1 antagonist L-733,060 facilitates sequence learning

2023

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Role of the substance P in learning and memory

Favila,

Overton

2025

Substance P

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Role of the basal ganglia in innate and learned behavioural sequences

Favila

Gurney

Overton

2023

Reviews in the Neurosciences

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Integrating individual actions into coherent, organised behavioural units, a process called chunking, is a fundamental, evolutionarily conserved process that renders actions automatic. In vertebrates, evidence points to the basal ganglia – a complex network believed to be involved in action selection – as a key component of action sequence encoding, although the underlying mechanisms are only just beginning to be understood. Central pattern generators control many innate automatic behavioural sequences that form some of the most basic behaviours in an animal’s repertoire, and in vertebrates, brainstem and spinal pattern generators are under the control of higher order structures such as the basal ganglia. Evidence suggests that the basal ganglia play a crucial role in the concatenation of simpler behaviours into more complex chunks, in the context of innate behavioural sequences such as chain grooming in rats, as well as sequences in which innate capabilities and learning interact such as birdsong, and sequences that are learned from scratch, such as lever press sequences in operant behaviour. It has been proposed that the role of the striatum, the largest input structure of the basal ganglia, might lie in selecting and allowing the relevant central pattern generators to gain access to the motor system in the correct order, while inhibiting other behaviours. As behaviours become more complex and flexible, the pattern generators seem to become more dependent on descending signals. Indeed, during learning, the striatum itself may adopt the functional characteristics of a higher order pattern generator, facilitated at the microcircuit level by striatal neuropeptides.

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Blocking NK1 receptors disrupts the sequential and temporal organization of chain grooming in rats

Cited by 3 publications

References 72 publications

The NK1 antagonist L-733,060 facilitates sequence learning

The NK1 antagonist L-733,060 facilitates sequence learning

Role of the substance P in learning and memory

Role of the basal ganglia in innate and learned behavioural sequences

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