QM/NN QSPR models with error estimation: vapor pressure and logP

QSPR models for logP and vapor pressures of organic compounds based on neural net interpretation of descriptors derived from quantum mechanical (semiempirical MO; AM1) calculations are presented. The models are cross-validated by dividing the compound set into several equal portions and training several individual multilayer feedforward neural nets (trained by the back-propagation of errors algorithm), each with a different portion as test set. The results of these nets are combined to give a mean predicted property value and a standard deviation. The performance of two models, for logP and the vapor pressure at room temperature, is analyzed, and the reliability of the predictions is tested.

Transient and persistent consequences of acute stress on long-term potentiation (LTP), synaptic efficacy, theta rhythms and bursts in area CA1 of the hippocampus.

Previous studies reported that exposure to an acute stressor of restraint and intermittent tailshock impairs long-term potentiation (LTP) in area CA1 of the rat hippocampus. In the first experiment, the longevity of the stress-induced impairment of LTP was determined. LTP of the excitatory postsynaptic potential (EPSP) was impaired 2 but not 4 days after stressor cessation. Exposure to the stressor also persistently enhanced the synaptic response to the tetanic stimulation patterned after theta rhythm activity (10, 100 Hz bursts delivered at 5 Hz). In a second experiment, we tested the hypothesis that exposure to the stressor enhanced synaptic efficacy itself. EPSPs were recorded from freely moving rats before, during and after stressor exposure. The synaptic response was not enhanced during stressor exposure. Instead, cessation of the stressor (and perhaps movement associated with release from restraint) induced a transient (< 2 min) decrease in synaptic efficacy. To determine whether exposure to the stressor enhances endogenous theta rhythms in area CA1, electroencephalographic (EEG) recordings were obtained from freely moving rats before, during and after exposure to the stressor. The power of theta (4-8 Hz) and low frequency (0.1-3.9 Hz) activity was enhanced in response to the tailshock aspect of the stressor. Together, the results indicate that exposure to an acute stressful event increases theta activity and its cessation transiently decreases synaptic efficacy. These transient effects are succeeded by a persistently sensitized response to theta burst stimulation and impaired LTP.

Opioid receptor-dependent long-term potentiation at the lateral perforant path-CA3 synapse in rat hippocampus.

The involvement of opioid receptors in the induction of long-term potentiation (LTP) was investigated in the lateral and medial perforant path projections to area CA3 of the hippocampus in anesthetized rats. The opioid receptor antagonist naloxone (10 nmol), applied to the hippocampal CA3 region 10 min prior to tetanization, blocked the induction lateral perforant path-CA3 LTP induced by high-frequency stimulation. By contrast, LTP induction in medial perforant path-CA3 was not attenuated by a 10 nmol quantity of naloxone. (+)-Naloxone (10 nmol), the inactive stereoisomer of naloxone, was without effect on the induction of lateral perforant path-CA3 LTP. Naloxone applied 1 h following LTP induction did not reverse established lateral perforant path-CA3 LTP, indicating that opioid receptors are involved in the induction but not the maintenance of LTP in this pathway. LTP of medial perforant path responses developed immediately, while LTP of lateral perforant path responses was slow to develop. The latter pattern is similar to the time course of the development of LTP observed at the mossy fiber-CA3 synapse and suggests that lateral and medial perforant path synapses may use distinct mechanisms of both induction and expression of LTP. These data extend previous findings demonstrating opioid receptor-dependent mechanisms of LTP induction at both the mossy fiber-CA3 synapse and the lateral perforant path-dentate gyrus synapse. We suggest that lateral perforant path and mossy fiber synapses may utilize similar, opioid receptor-dependent, mechanisms of LTP induction and expression.