Spaced training induces normal long-term memory in CREB mutant mice.

BACKGROUND: The cAMP responsive element binding protein (CREB) is a transcription factor the activity of which is modulated by increases in the intracellular levels of cAMP and calcium. Results from studies with Aplysia, Drosophila and mice indicate that CREB-activated transcription is required for long-term memory. Furthermore, a recent study found that long-term memory for olfactory conditioning can be induced with a single trial in transgenic Drosophila expressing a CREB activator, whereas in normal flies, with presumably lower CREB-mediated transcription levels, conditioning requires multiple spaced trials. This suggests that CREB-mediated transcription is important in determining the type of training required for long-term memory of olfactory conditioning in Drosophila. Interestingly, studies with cultured Aplysia neurons indicated that removing a CREB repressor promoted the formation of long-term facilitation, a cellular model of non-associative memory. RESULTS: Here, we have confirmed that mice lacking the alpha and Delta CREB proteins (CREBalphaDelta-) have abnormal long-term, but not short-term, memory, as tested in an ethologically meaningful task. Importantly, additional spaced training can overcome the profound memory deficits of CREBalphaDelta- mutants. Increasing the intertrial interval from 1 to 60 minutes overcame the memory deficits of the CREBalphaDelta- mice in three distinct behavioral tasks: contextual fear conditioning, spatial learning and socially transmitted food preferences. CONCLUSIONS: Previous findings and results presented here demonstrate that CREB mutant mice have profound long-term memory deficits. Importantly, our findings indicate that manipulations of CREB function can affect the number of trials and the intertrial interval required for committing information to long-term memory. Remarkably, this effect of CREB function is not restricted to simple conditioning tasks, but also affects complex behaviours such as spatial memory and memory for socially transmitted food preferences.

(University of Pennsylvania Case Conference): oligoclonal immunoglobulins in cerebrospinal fluid in multiple sclerosis.

In the normal state, immunoglobulins are polyclonal. They migrate as a broad band on electrophoresis, reflecting the diversity of immunoglobulin species secreted by the many clones of immunoglobulin-producing cells. In lymphoproliferative disorders, monoclonal immunoglobulins are often found, migrating as electrophoretically homogeneous bands, reflecting the large amount of a single immunoglobulin being secreted by the single proliferating neoplastic clone. In certain neurological diseases, such as multiple sclerosis, the cerebrospinal fluid (CSF)2 often exhibits an oligoclonal immunoglobulin pattern consisting of several electrophoretically homogeneous bands in the gamma-globulin regin (Figure 1). We present two cases of neurological disease with an oligoclonal immunoglobulin pattern in the CSF electropherogram. In the discussion we consider the definition, etiology, and pathogenesis of multiple sclerosis, and laboratory tests that are useful in multiple sclerosis, emphasizing methods for the demonstration and interpretation of an oligoclonal immunoglobulin pattern.