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The role of glutamate receptor-dependent signaling in the dopamine system in reinforcement learning and adaptive decision-making

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Cieslak P. E.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

Midbrain dopamine (DA) neurons, together with the major target of their projections – dopaminoceptive neurons in the frontal cortex and basal ganglia, provide a neural substrate for reinforcement learning and are involved in decision-making and action selection. Activity and plasticity in the DA system is largely dependent on excitatory glutamatergic transmission. Here, we sought to determine the role of glutamate receptors in the DA system by using genetically modified mice with cell‑type specific ablation of NMDA or mGluR5 receptors in DA neurons and neurons expressing dopamine D1 receptors. Animals were tested in an adaptive decision-making task, that resembles a ‘two-armed bandit problem’, in which mouse is required to estimate by trial-and-error expected value of two alternatives associated with different reward probabilities (80% vs. 20%). During each session reward probabilities were reversed after 60 trials. In order to maximize the long-term sum of rewards, a mouse had to select alternative with higher success probability and adapt their choices to changes in reward contingencies. We observed that disruption of NMDA receptor-dependent signaling in DA neurons caused an initial impairment in error-driven learning and reduced the likelihood of returning to previously rewarded alternative. Moreover, loss of mGluR5 but not NMDA receptors in D1 receptor-expressing neurons decreased reward sensitivity, and as a consequence frequency of choosing alternative with higher reward probability. Finally, loss of NMDA receptors in DA neurons and mGluR5 receptors in D1 neurons caused a delay in decision time and increased latency to collect reward. In conclusion, our results suggest that glutamate receptor-dependent signaling in the DA system is necessary for quick and optimal decision-making. FINANCIAL SUPPORT: National Science Centre grant PRELUDIUM 2014/15/N/NZ4/00761.

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Behavioral flexibility in mice with selective inactivation of NMDA receptors in the dopamine system

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Cieslak P. E., Lopata K., Rodriguez Parkina J.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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nr 3

Goal-directed behavior requires flexibility, the ability to adjust behavior in response to changing environmental circumstances. This flexibility is mediated by the prefrontal cortex and striatum of the brain and is strongly influenced by neurotransmitter dopamine, which modulates the balance between persistence and shifting of behavioral strategies. Here, we investigated behavioral flexibility in genetically modified mice, NR1DATCreERT2 and NR1D1CreERT2, lacking functional NMDA receptors in dopaminergic and dopaminoceptive (D1 expressing) neurons, respectively. We used a T-maze based task, which permits to examine the ability to learn and switch between two spatial maze tasks requiring different response strategies. In a visual cue task, mice had to make a turn toward the arm of the maze where the visual cue was placed to obtain food reward. After the switch to response direction task, animals had to make a turn based on direction (left or right, regardless of the visual cue). Loss of NMDA receptors in dopamine but not D1 expressing neurons disrupted shifting between strategies. Furthermore, analysis of arm choice errors revealed that the deficit was not due to perseveration of a strategy previously learned but due to impairments in acquisition of a new strategy. Supported by the grant OPUS 2011/03/B/NZ4/02211

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Phenotyping reward-driven behaviors in transgenic mice

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Lopata K., Cieslak P. E., Turbasa M., Rodrigez Parkitna J.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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nr 3

The dopamine neurons of the ventral midbrain form the core of the brain’s reward system and the plasticity of these neurons are essential in mediating the effects of positive reinforcement. To study the underlying neuronal mechanisms we used genetically modified mice (NR1DATCreERT2) that lacked NMDA glutamate receptors on dopamine neurons and thus had impaired plasticity on excitatory synapses. We found that mutant mice performed similarly as controls in food-self administration test under fixed, progressive or variable interval schedules. However, NR1DATCreERT2 mice failed to acquire instrumental responding for sensory stimuli in the operant sensation seeking test. Furthermore, when mice were tested for sweet taste preference under instrumental access (FR3) in an IntelliCage, mutants did not prefer the saccharine solution over pure water (52±11%) while control animals reached 98±13% preference. The anhedonia-like phenotype prompted us to test the animals in forced swimming test and we found that NR1DATCreERT2 animals spent more time immobile than controls. In summary, we believe that the loss of NMDA receptors on dopamine neurons caused decreased sensitivity to sensory stimuli, anhedonia and increased learned helplessness, without causing obvious impairments in instrumental learning. Supported by the grant OPUS 2011/03/B/NZ4/02211

Ograniczanie wyników

3 Acta Neurobiologiae Experimentalis

3 Cieslak P. E.

2 Lopata K.

1 Rodrigez Parkitna J.

1 Rodriguez Parkina J.

1 Turbasa M.

1 2017

2 2014

The role of glutamate receptor-dependent signaling in the dopamine system in reinforcement learning and adaptive decision-making

Behavioral flexibility in mice with selective inactivation of NMDA receptors in the dopamine system

Phenotyping reward-driven behaviors in transgenic mice