Improvement in fear memory by histamine-elicited ERK2 activation in hippocampal CA3 cells.

Consolidation of associative memories appears to require extracellular signal-related kinase2 (ERK2) activation, which is modulated by several factors, including neurotransmitter receptor stimulation. Here we show that in vitro stimulation of either H2 or H3 histaminergic receptors activates ERK2 in hippocampal CA3 pyramidal cells. In behaving animals, bilateral posttraining injections into the dorsal hippocampus of histamine H2 or H3 receptor agonists improve memory consolidation after contextual fear conditioning. Local administration of U0126, a selective inhibitor of ERK kinase, prevents memory improvements exerted by the agonists, without causing any behavioral effect per se. This is the first evidence of a positive correlation between ERK phosphorylation and memory improvement. Moreover, we demonstrate that the brain histaminergic system regulates hippocampal ERK cascade. Finally, our data indicate that early ERK2 hippocampal activation is not required for the expression of long-term fear memories.

Spatial navigation in the Morris water maze: working and long lasting reference memories.

Spatial navigation development in the Morris water maze (MWM) paradigm was studied in 70-day-old male Long-Evans hooded rats. During 5 consecutive days, rats' training consisted of a daily block of 10 trials. Escape latency was measured in each trial. Probe testing was performed every day immediately before and after the daily block of trials. In addition, a final probe was performed on Day 6. During the first 3 days of training, the escape latency became progressively shorter, showing an asymptotic trend on Days 4 and 5. Probe trials administered at the end of the first acquisition sessions showed clear preference for the target quadrant but this information was not recalled at probe trials given 24h later. The memory trace retrieved after 24-h delay was formed only after 30 trials received over three sessions. The probe trial given at the end of an acquisition session tests the efficiency of the working memory whereas the 24h delayed probe trial reflects better-consolidated spatial information corresponding to long lasting reference memory. It can be noted that the progressive shortening of escape latencies does not express closely the evolution of the rat's long lasting (consolidated) reference memory. This memory can be satisfactorily measured only by probe testing performed at an adequate delay after training. These considerations may be of some interest when interpreting the rat's performance in the MWM.