Kenneth Light

Impaired Working Memory Duration But Normal Learning Abilities Found in Mice That Are Conditionally Deficient in the Close Homolog of L1

In addition to its role in axon growth and neuronal migration, the close homolog of L1 (CHL1), a member of the L1 family of cell adhesion molecules, is involved in synaptic plasticity. To date, little has been done to disassociate the role of CHL1 during adulthood from its role during development. To address this issue, mice conditionally deficient in CHL1 (lacking CHL1 only after the third postnatal week) were tested relative to littermate controls as adults in five learning tasks and several tests of working memory (including duration and selective attention). CHL1-deficient mice showed no impairments in the learning tasks compared with wild-type controls. CHL1 deletion had no effect on selective attention despite its widespread impairment of working memory duration. These results suggest a role for CHL1 in the adult-brain in the short-term maintenance of information.

Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities

BackgroundPEA-15 is a phosphoprotein that binds and regulates ERK MAP kinase and RSK2 and is highly expressed throughout the brain. PEA-15 alters c-Fos and CREB-mediated transcription as a result of these interactions. To determine if PEA-15 contributes to the function of the nervous system we tested mice lacking PEA-15 in a series of experiments designed to measure learning, sensory/motor function, and stress reactivity.ResultsWe report that PEA-15 null mice exhibited impaired learning in three distinct spatial tasks, while they exhibited normal fear conditioning, passive avoidance, egocentric navigation, and odor discrimination. PEA-15 null mice also had deficient forepaw strength and in limited instances, heightened stress reactivity and/or anxiety. However, these non-cognitive variables did not appear to account for the observed spatial learning impairments. The null mice maintained normal weight, pain sensitivity, and coordination when compared to wild type controls.ConclusionWe found that PEA-15 null mice have spatial learning disabilities that are similar to those of mice where ERK or RSK2 function is impaired. We suggest PEA-15 may be an essential regulator of ERK-dependent spatial learning.