The Rho GTPase activating CNF1 improves associative working memory for object-in-place.
Cerebral Rho GTPases are crucially involved in cognitive abilities. This activity is thought to be related to the regulation of actin polymerization and, thereby, of the shape of the dendritic tree. Here we report that Cytotoxic Necrotizing Factor 1 (CNF1, 1fmol/kgicv), a bacterial protein endowed with Rho GTPase activating properties, enhances working memory for object location/discrimination in C57BL/6 mice. CNF1 selectively increased the exploration of a specific familiar object moved to a position that had been previously occupied by another familiar object. Conversely, the treatment left unaffected (i) exploration of a familiar object moved to a location that was previously unoccupied and (ii) exploration of a novel object. The effects were associated with changes in Rho GTPase status, since CNF1 C866S, a recombinant CNF1 in which the enzymatic activity was abolished through substitution of serine to cysteine at position 866, was ineffective in all the experiments. The study suggests that working memory for specific object-location associations critically depends on neural connectivity. It also confirms the therapeutic potential of the manipulation of Rho GTPase signaling in the modulation of memory processes.
De Viti
Silvia
S
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Roma, Italy.
Martino
Assunta
A
Musilli
Marco
M
Fiorentini
Carla
C
Diana
Giovanni
G
D000704:Analysis of Variance; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects*
D001427:Bacterial Toxins; D020536:Enzyme Activators; D029968:Escherichia coli Proteins; C060296:cytotoxic necrotizing factor type 1