To investigate the function of the alpha calcium-calmodulin-dependent kinase II (alphaCaMKII) inhibitory autophosphorylation at threonines 305 and/or 306, we generated knockin mice that express alphaCaMKII that cannot undergo inhibitory phosphorylation. In addition, we generated mice that express the inhibited form of alphaCaMKII, which resembles the persistently phosphorylated kinase at these sites. Our data demonstrate that blocking inhibitory phosphorylation increases CaMKII in the postsynaptic density (PSD), lowers the threshold for hippocampal long-term potentiation (LTP), and results in hippocampal-dependent learning that seems more rigid and less fine-tuned. Mimicking inhibitory phosphorylation dramatically decreased the association of CaMKII with the PSD and blocked both LTP and learning. These data demonstrate that inhibitory phosphorylation has a critical role in plasticity and learning.

Aging is associated with spatial memory impairments and with deficient encoding of information by the hippocampus. In young adult rats, recent studies on the firing properties of hippocampal neurons have emphasized the importance of the CA3 subregion in the rapid encoding of new spatial information. Here, we compared the spatial firing patterns of CA1 and CA3 neurons in aged memory-impaired rats with those of young rats as they explored familiar and novel environments. We found that CA1 place cells in aged and young rats had similar firing characteristics in the familiar and novel environments. In contrast, aged CA3 place cells had higher firing rates in general and failed to change their firing rates and place fields as much as CA3 cells of young rats when the rats were introduced to a novel environment. Thus, aged CA3 cells failed to rapidly encode new spatial information compared with young CA3 cells. These data suggest an important and selective contribution of CA3 dysfunction to age-related memory impairment.

ABSTRACT. Objectives. The aims of this prospective nationwide investigation were to establish the birth rate, mortality, and morbidity of extremely low birth weight (ELBW) infants in Finland in 1996 -1997, and to analyze risk factors associated with poor outcome.Participants and Methods. The study population included all stillborn and live-born ELBW infants (birth weight: <1000 g; gestational age: at least 22 gestational weeks [GWs]), born in Finland between January 1, 1996 and December 31, 1997. Surviving infants were followed until discharge or to the age corresponding with 40 GWs. National ELBW infant register data with 101 prenatal and postnatal variables were used to calculate the mortality and morbidity rates. A total of 32 variables were included in risk factor analysis. The risk factors for death and intraventricular hemorrhage (IVH) of the live-born infants as well as for retinopathy of prematurity (ROP) and oxygen dependency of the surviving infants were analyzed using logistic regression models.Results. A total of 529 ELBW infants (.4% of all newborn infants) were born during the 2-year study. The perinatal mortality of ELBW infants was 55% and accounted for 39% of all perinatal deaths. Of all ELBW infants, 34% were stillborn, 21% died on days 0 through 6, and 3% on days 7 though 28. Neonatal mortality was 38% and postneonatal mortality was 2%. Of the infants who were alive at the age of 4 days, 88% survived. In infants surviving >12 hours, the overall incidence of respiratory distress syndrome (RDS) was 76%; of blood culture-positive septicemia, 22%; of IVH grades II through IV, 20%; and of necrotizing enterocolitis (NEC) with bowel perforation, 9%. The rate of IVH grades II through IV and NEC with bowel perforation decreased with increasing gestational age, but the incidence of RDS did not differ significantly between GWs 24 to 29. A total of 5 infants (2%) needed a shunt operation because of posthemorrhagic ventricular dilatation. Two hundred eleven ELBW infants (40% of all and 60% of live-born infants) survived until discharge or to the age corresponding with 40 GWs. The oxygen dependency rate at the age corresponding to 36 GWs was 39%, and 9% had ROP stage III-V. Neurological status was considered completely normal in 74% of the surviving infants. The proportions of infants born at 22 to 23, 24 to 25, 26 to 27, and 28 to 29 GWs with at least one disability (ROP, oxygen dependency, or abnormal neurological status) at the age corresponding to 36 GWs were 100%, 62%, 51%, and 45%, respectively. Birth weight <600 g and gestational age <25 GWs were the independent risks for death and short-term disability. The primary risk factor for IVH grades II through IV was RDS. Low 5-minute Apgar scores predicted poor prognosis, ie, death or IVH, and antenatal steroid treatment to mothers with threatening premature labor seemed to protect infants against these. Some differences were found in the mortality rates between the 5 university hospital districts: neonatal mortality was significantly lower (25% vs 44%) in...

No abstract

Spatial learning impairment in aged rats is associated with changes in hippocampal connectivity and plasticity. Several studies have explored the age-related deficit in spatial information processing by recording the location-specific activity of hippocampal neurons (place cells). However, these studies have generated disparate characterizations of place cells in aged rats as unstable ( . To reconcile these findings, we recorded place cells from aged and young rats as they repeatedly explored both a highly familiar environment and an initially novel environment, and we repeatedly tested whether the place fields formed in the novel environment were anchored by external cues. Initially, spatial representations in aged rats were abnormally maintained between the familiar and novel environments. Then, new representations were formed but were also delayed in becoming anchored to the external landmarks. Finally, even when the new spatial representations became bound to the landmarks, they were multi-stable across repetitive exposures to the formerly novel environment. These observations help to reconcile previously divergent characterizations of spatial representation in aged rats and suggest a model of cognitive aging and hippocampal function.

No abstract

No abstract

The role of the basal forebrain cholinergic system in hippocampal spatial representation was explored by examining the effects of immunotoxic lesions of the septo-hippocampal cholinergic neurons on the firing patterns of hippocampal place cells as rats explored familiar and novel environments. In a highly familiar environment, the basic qualities and stability of place fields were unaffected by the lesion. When first exposed to a set of novel environmental cues without otherwise disorienting the animals, place cells in both normal and lesioned animals responded with similar alterations in their firing patterns. Upon subsequent repetitive exposures to the new environment, place cells of normal rats developed a spatial representation distinct from that of the familiar environment. By contrast, place cells of lesioned animals reconverged in the direction of the representation associated with the familiar environment. These results suggest that cholinergic input may determine whether new visual information or a stored representation of the current environment will be actively processed in the hippocampal network.