Dissociative Effects of Neuropeptide S Receptor Deficiency and Nasal Neuropeptide S Administration on T-Maze Discrimination and Reversal Learning

Ahmet Oguzhan Bicakci; Pei-Ling Tsai; Evelyn Kahl; Dana Mayer; Markus Fendt

doi:10.3390/ph14070643

Dissociative Effects of Neuropeptide S Receptor Deficiency and Nasal Neuropeptide S Administration on T-Maze Discrimination and Reversal Learning

Pharmaceuticals ◽

10.3390/ph14070643 ◽

2021 ◽

Vol 14 (7) ◽

pp. 643

Author(s):

Ahmet Oguzhan Bicakci ◽

Pei-Ling Tsai ◽

Evelyn Kahl ◽

Dana Mayer ◽

Markus Fendt

Keyword(s):

Locomotor Activity ◽

Discrimination Learning ◽

Cognitive Flexibility ◽

Reversal Learning ◽

Learning Strategy ◽

Brain Regions ◽

Nasal Administration ◽

Neuropeptide S ◽

Laboratory Rodents

Cognitive flexibility refers to the ability to modify learned behavior in response to changes in the environment. In laboratory rodents, cognitive flexibility can be assessed in reversal learning, i.e., the change of contingencies, for example in T-maze discrimination learning. The present study investigated the role of the neuropeptide S (NPS) system in cognitive flexibility. In the first experiment, mice deficient of NPS receptors (NPSR) were tested in T-maze discrimination and reversal learning. In the second experiment, C57BL/6J mice were tested in the T-maze after nasal administration of NPS. Finally, the effect of nasal NPS on locomotor activity was evaluated. NPSR deficiency positively affected the acquisition of T-maze discrimination but had no effects on reversal learning. Nasal NPS administration facilitated reversal learning and supported an allocentric learning strategy without affecting acquisition of the task or locomotor activity. Taken together, the present data show that the NPS system is able to modulate both acquisition of T-maze discrimination and its reversal learning. However, NPSR deficiency only improved discrimination learning, while nasal NPS administration only improved reversal learning, i.e., cognitive flexibility. These effects, which at first glance appear to be contradictory, could be due to the different roles of the NPS system in the brain regions that are important for learning and cognitive flexibility.

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Cortical and thalamic influences on striatal involvement in instructed, serial reversal learning; implications for the organisation of flexible behaviour.

10.1101/2021.12.20.472804 ◽

2021 ◽

Author(s):

Brendan Williams ◽

Anastasia Christakou

Keyword(s):

Functional Connectivity ◽

Cognitive Flexibility ◽

Reversal Learning ◽

Orbitofrontal Cortex ◽

Dorsal Striatum ◽

Response Strategy ◽

Flexible Control ◽

The Right ◽

Serial Reversal

Cognitive flexibility is essential for enabling an individual to respond adaptively to changes in their environment. Evidence from human and animal research suggests that the control of cognitive flexibility is dependent on an array of neural architecture. Cortico-basal ganglia circuits have long been implicated in cognitive flexibility. In particular, the role of the striatum is pivotal, acting as an integrative hub for inputs from the prefrontal cortex and thalamus, and modulation by dopamine and acetylcholine. Striatal cholinergic modulation has been implicated in the flexible control of behaviour, driven by input from the centromedian-parafascicular nuclei of the thalamus. However, the role of this system in humans is not clearly defined as much of the current literature is based on animal work. Here, we aim to investigate the roles corticostriatal and thalamostriatal connectivity in serial reversal learning. Functional connectivity between the left centromedian-parafascicular nuclei and the associative dorsal striatum was significantly increased for negative feedback compared to positive feedback. Similar differences in functional connectivity were observed for the right lateral orbitofrontal cortex, but these were localised to when participants switched to using an alternate response strategy following reversal. These findings suggest that connectivity between the centromedian-parafascicular nuclei and the striatum may be used to generally identify potential changes in context based on negative outcomes, and the effect of this signal on striatal output may be influenced by connectivity between the lateral orbitofrontal cortex and the striatum.

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Melamine disrupts spatial reversal learning and learning strategy via inhibiting hippocampal BDNF-mediated neural activity

PLoS ONE ◽

10.1371/journal.pone.0245326 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245326

Author(s):

Wei Sun ◽

Yuanhua Wu ◽

Dongxin Tang ◽

Xiaoliang Li ◽

Lei An

Keyword(s):

Cognitive Flexibility ◽

Reversal Learning ◽

Neural Activity ◽

Learning Strategy ◽

Learning Deficits ◽

Place Strategy ◽

Dependent Learning ◽

Dose Dependent Increase ◽

Dose Dependent

Although several studies showed adverse neurotoxic effects of melamine on hippocampus (HPC)-dependent learning and reversal learning, the evidence for this mechanism is still unknown. We recently demonstrated that intra-hippocampal melamine injection affected the induction of long-term depression, which is associated with novelty acquisition and memory consolidation. Here, we infused melamine into the HPC of rats, and employed behavioral tests, immunoblotting, immunocytochemistry and electrophysiological methods to sought evidence for its effects on cognitive flexibility. Rats with intra-hippocampal infusion of melamine displayed dose-dependent increase in trials to the criterion in reversal learning, with no locomotion or motivation defect. Compared with controls, melamine-treated rats avoided HPC-dependent place strategy. Meanwhile, the learning-induced BDNF level in the HPC neurons was significantly reduced. Importantly, bilateral intra-hippocampal BDNF infusion could effectively mitigate the suppressive effects of melamine on neural correlate with reversal performance, and rescue the strategy bias and reversal learning deficits. Our findings provide first evidence for the effect of melamine on cognitive flexibility and suggest that the reversal learning deficit is due to the inability to use place strategy. Furthermore, the suppressive effects of melamine on BDNF-mediated neural activity could be the mechanism, thus advancing the understanding of compulsive behavior in melamine-induced and other neuropsychiatric disorders.

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Maternal aggression in rodents: brain oxytocin and vasopressin mediate pup defence

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2013.0085 ◽

2013 ◽

Vol 368 (1631) ◽

pp. 20130085 ◽

Cited By ~ 94

Author(s):

Oliver J. Bosch

Keyword(s):

Brain Regions ◽

Maternal Behaviour ◽

Maternal Aggression ◽

Extrinsic Factors ◽

Intrinsic Factors ◽

Protective Behaviour ◽

Laboratory Rodents ◽

The Brain ◽

Extrinsic And Intrinsic Factors

The most significant social behaviour of the lactating mother is maternal behaviour, which comprises maternal care and maternal aggression (MA). The latter is a protective behaviour of the mother serving to defend the offspring against a potentially dangerous intruder. The extent to which the mother shows aggressive behaviour depends on extrinsic and intrinsic factors, as we have learned from studies in laboratory rodents. Among the extrinsic factors are the pups’ presence and age, as well as the intruders’ sex and age. With respect to intrinsic factors, the mothers’ innate anxiety and the prosocial brain neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) play important roles. While OXT is well known as a maternal neuropeptide, AVP has only recently been described in this context. The increased activities of these neuropeptides in lactation are the result of remarkable brain adaptations peripartum and are a prerequisite for the mother to become maternal. Consequently, OXT and AVP are significantly involved in mediating the fine-tuned regulation of MA depending on the brain regions. Importantly, both neuropeptides are also modulators of anxiety, which determines the extent of MA. This review provides a detailed overview of the role of OXT and AVP in MA and the link to anxiety.

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Hyperlocomotion during Recovery from Isoflurane Anesthesia Is Associated with Increased Dopamine Turnover in the Nucleus Accumbens and Striatum in Mice

Anesthesiology ◽

10.1097/00000542-199702000-00022 ◽

1997 ◽

Vol 86 (2) ◽

pp. 464-475 ◽

Cited By ~ 25

Author(s):

Masahiro Irifune ◽

Tomoaki Sato ◽

Takashige Nishikawa ◽

Takashi Masuyama ◽

Masahiro Nomoto ◽

...

Keyword(s):

Locomotor Activity ◽

Nucleus Accumbens ◽

High Performance ◽

Gas Flow ◽

Brain Regions ◽

Dopamine Neurons ◽

Dopamine Turnover

Background It was recently reported that isoflurane increases dopamine release in the striatum in rats both in vivo and in vitro, and that isoflurane inhibits uptake of dopamine in the rat brain synaptosomes. However, the functional role of these effects of isoflurane on dopamine neurons is uncertain. Dopaminergic mechanisms within the nucleus accumbens and striatum play an important role in the control of locomotor activity, and a change in dopamine turnover depends essentially on a change in impulse flow in the dopamine neurons. In this study, the effects of isoflurane on locomotor activity and on dopamine turnover were investigated in discrete brain regions in mice. Methods Mice were placed in individual airtight clear plastic chambers and spontaneously breathed isoflurane in 25% oxygen and 75% nitrogen (fresh gas flow, 4 l/min). Locomotor activity was measured with an Animex activity meter. Animals were decapitated after treatments with or without isoflurane, and the concentrations of monoamines and their metabolites in different brain areas were measured by high-performance liquid chromatography. Results During the 10 min after the cessation of the 20-min exposure to isoflurane, there was a significant increase in locomotor activity in animals breathing 1.5% isoflurane but not 0.7% isoflurane. This increase in locomotor activity produced by 1.5% isoflurane was abolished by a low dose of haloperidol (0.1 mg/kg), a dopamine receptor antagonist. Regional brain monoamine assays revealed that 1.5% isoflurane significantly increased the 3,4-dihydroxyphenylacetic acid:dopamine ratio (one indicator of transmitter turnover) in the nucleus accumbens and striatum, but a concentration of 0.7% did not. This significant increase in dopamine turnover in these regions continued during 20 min after the cessation of the administration of 1.5% isoflurane. Conclusions These results suggest that isoflurane-induced hyperlocomotion during emergence may be associated with increased dopamine turnover in the nucleus accumbens and striatum.

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Role of the ecto-nucleotidases in the cooperative effect of adenosine and neuropeptide-S on locomotor activity in mice

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2011.06.028 ◽

2011 ◽

Vol 99 (4) ◽

pp. 726-730 ◽

Cited By ~ 9

Author(s):

Robson Pacheco ◽

Bruna Bardini Pescador ◽

Bruna Pescador Mendonça ◽

Saulo Fábio Ramos ◽

Remo Guerrini ◽

...

Keyword(s):

Locomotor Activity ◽

Cooperative Effect ◽

Neuropeptide S

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Astrocytes render memory flexible

10.1101/2021.03.25.436945 ◽

2021 ◽

Author(s):

Wuhyun Koh ◽

Mijeong Park ◽

Ye Eun Chun ◽

Jaekwang Lee ◽

Hyun soo Shim ◽

...

Keyword(s):

Cognitive Flexibility ◽

Reversal Learning ◽

Memory Formation ◽

Cellular Mechanism ◽

Pivotal Role ◽

Changing Environment ◽

Memory Acquisition

Cognitive flexibility is an essential ability to adapt to changing environment and circumstances. NMDAR has long been implicated in cognitive flexibility, but the precise molecular and cellular mechanism is not well understood. Here, we report that astrocytes regulate NMDAR tone through Best1-mediated glutamate and D-serine release, which is critical for cognitive flexibility. Co-release of D-serine and glutamate is required for not only homosynaptic LTD but also heterosynaptic LTD, which is induced at unstimulated synapses upon release of norepinephrine and activation of astrocytic α1-AR during homosynaptic LTP. Remarkably, heterosynaptic LTD at unstimulated synapses during memory acquisition is required for later repotentiation LTP during reversal learning, laying a foundation for flexible memory and cognitive flexibility. Our study sheds light on the pivotal role of astrocytes in orchestrating multiple synapses during memory formation and determining the fate of consolidated memory to be retained as a flexible memory.

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Frontoparietal action-oriented codes support novel instruction implementation

10.1101/830067 ◽

2019 ◽

Cited By ~ 1

Author(s):

Carlos González-García ◽

Silvia Formica ◽

David Wisniewski ◽

Marcel Brass

Keyword(s):

Cognitive Flexibility ◽

Crucial Role ◽

Brain Regions ◽

Behavioral Performance ◽

Task Execution ◽

Task Knowledge ◽

Stimulus Response ◽

Neural Architecture ◽

Pattern Tracking

AbstractA key aspect of human cognitive flexibility concerns the ability to convert complex symbolic instructions into novel behaviors. Previous research proposes that this transformation is supported by two neurocognitive states: an initial declarative maintenance of task knowledge, and an implementation state necessary for optimal task execution. Furthermore, current models predict a crucial role of frontal and parietal brain regions in this process. However, whether declarative and procedural signals independently contribute to implementation remains unknown. We report the results of an fMRI experiment in which participants executed novel instructed stimulus-response associations. We then used a pattern-tracking procedure to quantify the contribution of format-unique signals during instruction implementation. This revealed independent procedural and declarative representations of novel S-Rs in frontoparietal areas, prior to execution. Critically, the degree of procedural activation predicted subsequent behavioral performance. Altogether, our results suggest an important contribution of frontoparietal regions to the neural architecture that regulates cognitive flexibility.

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