Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory.

cAMP-dependent protein kinase (PKA) is critical for the expression of some forms of long-term potentiation (LTP) in area CA1 of the mouse hippocampus and for hippocampus-dependent memory. Exposure to spatially enriched environments can modify LTP and improve behavioral memory in rodents, but the molecular bases for the enhanced memory performance seen in enriched animals are undefined. We tested the hypothesis that exposure to a spatially enriched environment may alter the PKA dependence of hippocampal LTP. Hippocampal slices from enriched mice showed enhanced LTP following a single burst of 100-Hz stimulation in the Schaffer collateral pathway of area CA1. In slices from nonenriched mice, this single-burst form of LTP was less robust and was unaffected by Rp-cAMPS, an inhibitor of PKA. In contrast, the enhanced LTP in enriched mice was attenuated by Rp-cAMPS. Enriched slices expressed greater forskolin-induced, cAMP-dependent synaptic facilitation than did slices from nonenriched mice. Enriched mice showed improved memory for contextual fear conditioning, whereas memory for cued fear conditioning was unaffected following enrichment. Our data indicate that exposure of mice to spatial enrichment alters the PKA dependence of LTP and enhances one type of hippocampus-dependent memory. Environmental enrichment can transform the pharmacological profile of hippocampal LTP, possibly by altering the threshold for activity-dependent recruitment of the cAMP-PKA signaling pathway following electrical and chemical stimulation. We suggest that experience-dependent plasticity of the PKA dependence of hippocampal LTP may be important for regulating the efficacy of hippocampus-based memory.

Clinical significance of pericardial effusion after heart transplantation.

Fifty-two consecutive patients who underwent orthotopic heart transplantation at our institution were evaluated by two-dimensional (2D) echocardiography at frequent intervals for 12 weeks after transplantation and at three monthly intervals for 1 year. Thirty-eight of 52 patients had adequate 2D echocardiograms and comprised the retrospective study group. Pericardial effusion was documented in 15 of 38 patients (40%). Pericardial effusion was moderate in two (5%) and small in seven patients (18%). Large pericardial effusion was demonstrated in six of 38 patients (16%). Three of 38 patients (8%) developed cardiac tamponade manifested by hypotension in the presence of a large pericardial effusion. The diagnosis of cardiac tamponade was aided by 2D echocardiography leading to prompt pericardiocentesis. The presence of pericardial effusion in patients after their transplantation did not demonstrate independent correlation with chest tube output after operation, cyclosporine therapy, acute rejection, level of blood urea nitrogen (BUN), infection or preoperative diagnosis of idiopathic dilated cardiomyopathy. The presence of cyclosporine therapy, acute rejection, and a preoperative diagnosis of idiopathic dilated cardiomyopathy, however, yielded an 86% probability of having pericardial effusion. Follow-up 2D echocardiograms obtained 301 +/- 106 days after transplantation were available in 25 patients. Fifteen patients (60%) had no pericardial effusion present on either the initial or follow-up 2D echocardiogram. The majority of cases of the pericardial effusion present on initial or follow-up echocardiograms were resolving on the follow-up study.(ABSTRACT TRUNCATED AT 250 WORDS)