title: Hippocampal-dependent spatial memory functions might be lateralized in rats: An approach combining gene expression profiling and reversible inactivation.
abstract: The hippocampus is involved in spatial memory processes, as established in a variety of species such as birds and mammals including humans. In humans, some hippocampal-dependent memory functions may be lateralized, the right hippocampus being predominantly involved in spatial navigation. In rodents, the question of possible lateralization remains open. Therefore, we first microdissected the CA1 subregion of the left and right dorsal hippocampi for analysis of mRNA expression using microarrays in rats having learnt a reference memory task in the Morris water-maze. Relative to untrained controls, 623 genes were differentially expressed in the right hippocampus, against only 74 in the left hippocampus, in the rats that had learnt the hidden platform location. Thus, in the right hippocampus, 299 genes were induced, 324 were repressed, and about half of them participate in signaling and transport, metabolism, and nervous system functions. In addition, most differentially expressed genes associated with spatial learning have been previously related to synaptic plasticity and memory. We then subjected rats to unilateral (left or right) or bilateral reversible functional inactivations in the dorsal hippocampus; lidocaine was infused either before each acquisition session or before retrieval of a reference spatial memory in the Morris water maze. We found that after drug-free acquisition, right or bilateral lidocaine inactivation (vs. left, or bilateral phosphate buffered saline (PBS) infusions) of the dorsal hippocampus just before a delayed (24 h) probe trial impaired performance. Conversely, left or bilateral hippocampus inactivation (vs. right, or bilateral PBS infusions) before each acquisition session weakened performance during a delayed, drug-free probe trial. Our data confirm a functional association between transcriptional activity within the dorsal hippocampus and spatial memory in the rat. Further, they suggest that there could be a leftward bias of hippocampal functions in engram formation or information transfer, and a rightward bias in spatial memory storage/retrieval processes.
authors.affiliation: RCMG, F. Hoffmann-La Roche Limited, CH 4070 Basel, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Klur
authors.forename: Christophe
authors.initials: C
authors.lastname: Muller
authors.forename: Anne
authors.initials: A
authors.lastname: Pereira de Vasconcelos
authors.forename: Theresa
authors.initials: T
authors.lastname: Ballard
authors.forename: Joëlle
authors.initials: J
authors.lastname: Lopez
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Galani
authors.forename: Ulrich
authors.initials: U
authors.lastname: Certa
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Cassel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology; D005552:Forelimb; D007839:Functional Laterality / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D042282:Microdissection; D008845:Microinjections; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D002491:Central Nervous System Agents; D012333:RNA, Messenger; D008012:Lidocaine