The protein kinase C family of enzymes has been implicated in synaptic plas
ticity and memory in a wide range of animal species, but to date little inf
ormation has been available concerning specific roles for individual isofor
ms of this category of kinases. To investigate the role of the beta isoform
of PKC in mammalian learning, we characterized mice deficient in the PKC b
eta gene using anatomical, biochemical, physiological, and behavioral appro
aches. In our studies we observed that PKC beta was predominantly expressed
in the neocortex, in area CA1 of the hippocampus, and in the basolateral n
ucleus of the amygdala. Mice deficient in PKC beta showed normal brain anat
omy and normal hippocampal synaptic transmission, paired pulse facilitation
, and long-term potentiation and normal sensory and motor responses. The PK
C beta knock-out animals exhibited a loss of learning, however; they suffer
ed deficits in both cued and contextual fear conditioning. The PKC expressi
on pattern and behavioral phenotype in the PKCb knock-out animals indicate
a critical role for the b isoform of PKC in learning-related signal transdu
ction mechanisms, potentially in the basolateral nucleus of the amygdala.