The extracellular signal-regulated kinases (ERKs) are members of the mitoge
n-activated protein kinase (MAPK) superfamily of enzymes and have recently
garnered considerable attention in the field of learning and memory. ERK ac
tivation has been shown to be required for the induction of long-term poten
tiation (LTP) in the rat hippocampus and for the formation of associative a
nd spatial memories in both the rat and the mouse. However, the individual
roles for the two isoforms of ERK have yet to be deciphered. To investigate
the specific contribution of the ERK1 (p44) isoform of MAPK to mammalian l
earning, we performed a general behavioral and physiological characterizati
on of mice lacking the ERK1 gene. The ERK1-null animals demonstrated signif
icantly higher levels of activity in the open field test. However, we obser
ved no other discernible deficits in the ERK1 knockout mice in our behavior
al testing. Specifically, no differences were observed in the acquisition o
r retention (24 h and 2 wk after training) of either contextual or cue fear
conditioning between the ERK1(-/-) and their wild-type littermate controls
. In addition, no learning phenotype was observed in the passive avoidance
test. When hippocampal slices were analyzed, we found no deficits in baseli
ne synaptic transmission or in tetanus-induced LTP in hippocampal area CA1.
We found no apparent compensatory changes in the expression of ERK2 (p42 M
APK). We conclude that hippocampus and amygdala-dependent emotional learnin
g does not depend critically on the activity of ERK1.