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Published on: June 22, 2015
DNA targeting of rhinal cortex D2 receptor protein reversibly blocks learning of cues that predict reward
Zheng Liu1, Barry J Richmond, Elisabeth A Murray
1Laboratory of Neuropsychology, Clinical Neuroscience Branch, and Behavioral Endocrinology Branch, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Abstract:
When schedules of several operant trials must be successfully completed to obtain a reward, monkeys quickly learn to adjust their behavioral performance by using visual cues that signal how many trials have been completed and how many remain in the current schedule. Bilateral rhinal (perirhinal and entorhinal) cortex ablations irreversibly prevent this learning. Here, we apply a recombinant DNA technique to investigate the role of dopamine D2 receptor in rhinal cortex for this type of learning. Rhinal cortex was injected with a DNA construct that significantly decreased D2 receptor ligand binding and temporarily produced the same profound learning deficit seen after ablation. However, unlike after ablation, the D2 receptor-targeted, DNA-treated monkeys recovered cue-related learning after 11-19 weeks. Injecting a DNA construct that decreased N-methyl-d-aspartate but not D2 receptor ligand binding did not interfere with learning associations between the cues and the schedules. A second D2 receptor-targeted DNA treatment administered after either recovery from a first D2 receptor-targeted DNA treatment (one monkey), after N-methyl-d-aspartate receptor-targeted DNA treatment (two monkeys), or after a vector control treatment (one monkey) also induced a learning deficit of similar duration. These results suggest that the D2 receptor in primate rhinal cortex is essential for learning to relate the visual cues to the schedules. The specificity of the receptor manipulation reported here suggests that this approach could be generalized in this or other brain pathways to relate molecular mechanisms to cognitive functions.
Insights
Monkeys use visual cues to learn complex trial schedules. Dopamine D2 receptors in the rhinal cortex are crucial for this learning, with targeted DNA decreasing receptor function temporarily impairing performance.
Area of Science:
- Neuroscience
- Cognitive Science
- Molecular Biology
Background:
- Monkeys learn to use visual cues for complex operant trial schedules.
- Bilateral rhinal cortex ablations cause irreversible learning deficits in this task.
- The role of dopamine D2 receptors in rhinal cortex learning remains unclear.
Purpose of the Study:
- To investigate the role of dopamine D2 receptors in the primate rhinal cortex for cue-related learning.
- To explore the potential of recombinant DNA techniques for studying receptor function in vivo.
- To determine if dopamine D2 receptor manipulation in the rhinal cortex affects learning of trial schedules.
Main Methods:
- Recombinant DNA technology was used to inject DNA constructs into the rhinal cortex of monkeys.
- One DNA construct specifically decreased dopamine D2 receptor ligand binding.
- Another construct targeted N-methyl-D-aspartate receptors, serving as a control.
Main Results:
- Decreasing dopamine D2 receptor binding temporarily impaired cue-related learning, mimicking ablation effects.
- Unlike ablations, this deficit was reversible, with recovery observed within 11-19 weeks.
- Targeting N-methyl-D-aspartate receptors did not interfere with learning, highlighting D2 receptor specificity.
Conclusions:
- Dopamine D2 receptors in the primate rhinal cortex are essential for learning to associate visual cues with trial schedules.
- Recombinant DNA techniques offer a specific and potentially reversible method to study molecular mechanisms in cognitive functions.
- This approach can be generalized to investigate other receptor-ligand interactions in various brain pathways.
