Effects of lentivirus-mediated CREB expression in the dorsolateral striatum: memory enhancement and evidence for competitive and cooperative interactions with the hippocampus.
Neural systems specialized for memory may interact during memory formation or recall, and the results of interactions are important determinants of how systems control behavioral output. In two experiments, we used lentivirus-mediated expression of the transcription factor CREB (LV-CREB) to test if localized manipulations of cellular plasticity influence interactions between the hippocampus and dorsolateral striatum. In Experiment 1, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for response learning, and impairs memory for place learning. LV-CREB in the dorsolateral striatum had no effect on response learning, but impaired place memory; a finding consistent with competition between the striatum and hippocampus. In Experiment 2, we tested the hypothesis that infusion of LV-CREB in the dorsolateral striatum facilitates memory for cue learning, and impairs memory for contextual fear conditioning. LV-CREB in the dorsolateral striatum enhanced memory for cue learning and, in contrast to our prediction, also enhanced memory for contextual fear conditioning, consistent with a cooperative interaction between the striatum and hippocampus. Overall, the current experiments demonstrate that infusion of LV-CREB in the dorsolateral striatum (1) increases levels of CREB protein locally, (2) does not alter acquisition of place, response, cue, or contextual fear conditioning, (3) facilitates memory for cue learning and contextual fear conditioning, and (4) impairs memory for place learning. Taken together, the present results provide evidence that LV-CREB in the dorsolateral striatum can enhance memory formation and cause both competitive and cooperative interactions with the hippocampus.
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California.
Balachandar
B
Kathirvelu
Paul J
PJ
Colombo
D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology*; D005239:Fear / Q000502:physiology; D015870:Gene Expression; D005822:Genetic Vectors; D006624:Hippocampus / Q000502:physiology; D007858:Learning / Q000502:physiology; D016086:Lentivirus / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D055647:Rats, Transgenic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology
D017362:Cyclic AMP Response Element-Binding Protein; D011994:Recombinant Proteins
CREB; competitive interaction; cooperative interaction; hippocampus; dorsal striatum; lentivirus; multiple memory systems; place learning; response learning