Transgenic mice lacking NMDAR-dependent LTD exhibit deficits in behavioral flexibility.

While most studies have focused on the role of long-term potentiation in behavior, far less is known about the role of long-term depression (LTD). To examine the potential involvement of LTD in learning and memory, we generated transgenic mice that express a fragment of the SV40 small t antigen known to inhibit protein phosphatase 2A (PP2A). Small t antigen expression blocked both stimulus-induced and chemically induced NMDAR-dependent LTD at Schaffer collateral synapses but did not affect potentiation, depotentiation, or mGluR-dependent LTD.

Understanding and treating "first-episode" schizophrenia.

"First-episode schizophrenia" is a clinical and research term that often is used to emphasize the special issues that arise when working with this patient population. The notion that schizophrenia has an inexorable downhill course or is a deteriorating illness is being challenged by more sophisticated understanding of what happens before the initial episode and new understanding of the interactions between biologic vulnerabilities and specific environmental risk during adolescence and early adulthood, such as marijuana use. While the incidence rate of "first-episode" will make this a relatively small percentage of a usual clinical caseload, it is a critically important time for the future course of the illness.