期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 44, 页码 17163-17168出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0807749105
关键词
basal ganglia; cAMP response element-binding protein; habit; learning and memory; procedural learning
资金
- National Institutes of Health (NIH) [R01-45481, K08 MH081190]
- NARSAD
- APA/Wyeth Pharmaceuticals
- Tourette Syndrome Association of America
The multiple memory systems framework proposes that distinct circuits process and store different sorts of information; for example, spatial information is processed by a circuit that includes the hippocampus, whereas certain forms of instrumental conditioning depend on the striatum. Disruption of hippocampal function can enhance striatum-dependent learning in some paradigms, which has been interpreted as evidence that these systems can compete with one another in an intact animal. However, it remains unclear whether such competition can occur in the opposite direction, as suggested by the multiple memory systems framework, or is unidirectional. We addressed this question using lesions and genetic manipulations in mice. Impairment of dorsal striatal function with either excitotoxic lesions or transgenic inhibition of the transcription factor cAMP response element-binding protein, which disrupts striatal synaptic plasticity, impaired striatum-dependent cued learning but enhanced hippocampus-dependent spatial learning. Conversely, excitotoxic lesions of the dorsal hippocampus disrupted spatial learning and enhanced cued learning. This double dissociation demonstrates bidirectional competition that constitutes strong evidence for the parallel operation of distinct memory systems.
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