Knockdown of Nurr1 in the rat hippocampus: implications to spatial discrimination learning and memory.
Nurr1 expression is up-regulated in the brain following associative learning experiences, but its relevance to cognitive processes remains unclear. In these studies, rats initially received bilateral hippocampal infusions of control or antisense oligodeoxynucleotides (ODNs) 1 h prior to training in a holeboard spatial discrimination task. Such pre-training infusions of nurr1 antisense ODNs caused a moderate effect in learning the task and also impaired LTM tested 7 d later. In a second experiment, ODN infusions were given immediately after the animals had received two sessions of training, during which all animals showed normal learning. Although antisense treated rats were significantly impaired during the post-infusion stages of acquisition of the task, no group differences were observed during the LTM test given 7 d later. These animals were subjected 3 d later to reversal training in the same maze in the absence of any additional treatments. Remarkably, rats previously treated with antisense ODNs displayed perseveration: The animals were fixated with the previously learned pattern of baited holes, causing them to be significantly impaired in the extinction of acquired spatial preferences and future learning. We postulate that Nurr1 function in the hippocampus is important for normal cognitive processes.
Colón-Cesario
Wanda I
WI
Department of Biology, University of Puerto Rico, San Juan 00931-3360, Puerto Rico.
Martínez-Montemayor
Michelle M
MM
Morales
Sohaira
S
Félix
Jahaira
J
Cruz
Juan
J
Adorno
Monique
M
Pereira
Lixmar
L
Colón
Nydia
N
Maldonado-Vlaar
Carmen S
CS
Peña de Ortiz
Sandra
S
D000704:Analysis of Variance; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004193:Discrimination Learning / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013028:Space Perception / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology*; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors