A novel, rapidly acquired and persistent spatial memory task that induces immediate early gene expression.
BACKGROUND
The Morris water maze task is a hippocampus-dependent learning and memory test that typically takes between 3 days to 2 weeks of training. This task is used to assess spatial learning and induces the expression of genes known to be crucial to learning and memory in the hippocampus. A major caveat in the protocol is the prolonged duration of training, and difficulty of assessing the time during training in which animals have learned the task. We introduce here a condensed version of the task that like traditional water maze tasks, creates lasting hippocampus-dependent spatial cognitive maps and elicits gene expression following learning.


METHODS
This paradigm was designed for rats to quickly acquire a hippocampus-dependent spatial cognitive map and retain this memory for at least 24 hours. To accomplish this, we interspersed visible and hidden training trials, delivering them in a massed fashion so training takes a maximum of 15 minutes. Learning was assessed based on latencies to the platform during each training trial, as well as time spent in the goal quadrant during probe testing 30 minutes and 24 hours after training. Normal rats were compared to two impaired cohorts (rats with fimbria-fornix lesions and rats administered NMDA receptor antagonist (CPP)). To quantitate hippocampal expression of known learning genes, real-time polymerase chain reaction (RT-PCR) was performed on hippocampal cDNA.


RESULTS
We show that massed training using alternating visible and hidden training trials generates robust short-term working and long-term reference memories in rats. Like the traditional Morris water maze paradigm, this task requires proper hippocampal function, as rats with fimbria-fornix lesions and rats administered CPP fail to learn the spatial component of the task. Furthermore, training in this paradigm elicits hippocampal expression of genes upregulated following learning in a variety of spatial tasks: homer1a, cfos and zif268.


CONCLUSIONS
We introduce here a condensed version of the Morris water maze, which is like a traditional water maze paradigm, in that it is hippocampus-dependent, and elicits hippocampal expression of learning genes. However, this task is administered in 15 minutes and induces spatial memory for at least 24 hours.
Feldman
Lisa A
LA
Department of Neurology and Neurosurgery, McGill University and Montreal Neurological Institute, Montreal, Quebec H3A2B4, Canada.
Shapiro
Matthew L
ML
Nalbantoglu
Josephine
J
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects; D016762:Genes, fos; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D000072233:Homer Scaffolding Proteins; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D002352:Carrier Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D018691:Excitatory Amino Acid Antagonists; D000072233:Homer Scaffolding Proteins; D010879:Piperazines; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid