Year: 2008
Type: article
Abstract: How long-term memories are stored is a fundamental question in neuroscience. The first molecular mechanism for long-term memory storage in the brain was recently identified as the persistent action of protein kinase Mzeta (PKMzeta), an autonomously active atypical protein kinase C (PKC) isoform critical for the maintenance of long-term potentiation (LTP). PKMzeta maintains aversively conditioned associations, but what general form of information the kinase encodes in the brain is unknown. We first confirmed the specificity of the action of zeta inhibitory peptide (ZIP) by disrupting long-term memory for active place avoidance with chelerythrine, a second inhibitor of PKMzeta activity. We then examined, using ZIP, the effect of PKMzeta inhibition in dorsal hippocampus (DH) and basolateral amygdala (BLA) on retention of 1-d-old information acquired in the radial arm maze, water maze, inhibitory avoidance, and contextual and cued fear conditioning paradigms. In the DH, PKMzeta inhibition selectively disrupted retention of information for spatial reference, but not spatial working memory in the radial arm maze, and precise, but not coarse spatial information in the water maze. Thus retention of accurate spatial, but not procedural and contextual information required PKMzeta activity. Similarly, PKMzeta inhibition in the hippocampus did not affect contextual information after fear conditioning. In contrast, PKMzeta inhibition in the BLA impaired retention of classical conditioned stimulus-unconditioned stimulus (CS-US) associations for both contextual and auditory fear, as well as instrumentally conditioned inhibitory avoidance. PKMzeta inhibition had no effect on postshock freezing, indicating fear expression mediated by the BLA remained intact. Thus, persistent PKMzeta activity is a general mechanism for both appetitively and aversively motivated retention of specific, accurate learned information, but is not required for processing contextual, imprecise, or procedural information.
Source: PLoS Biology
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,500
Awards: G1545359851, Functional Grouping in Hippocampus, G2902798530, Spatial- Temporal Aspects of Drosophila Memory Formation, Regulation and Neural Function of Atypical PKC, Plasticity and learning in a corticostriatal network, Conjunctive Representations in Cortex and Hippocampus, Amygdaloid Function in Fear Conditioning, Protein Kinase C Isozymes in Hippocampal Plasticity, Mechanism Underlying Memory Stabilization, Regulation of Neural Function of Atypical PKC, Plasticity and learning in a corticostriatal network, G9000187146
OpenAlex ID: W2092112738