A. E. P. Villa

Parvalbumin deficiency affects network properties resulting in increased susceptibility to epileptic seizures

Networks of GABAergic interneurons are of utmost importance in generating and promoting synchronous activity and are involved in producing coherent oscillations. These neurons are characterized by their fast-spiking rate and by the expression of the Ca(2+)-binding protein parvalbumin (PV). Alteration of their inhibitory activity has been proposed as a major mechanism leading to epileptic seizures and thus the role of PV in maintaining the stability of neuronal networks was assessed in knockout (PV-/-) mice. Pentylenetetrazole induced generalized tonic-clonic seizures in all genotypes, but the severity of seizures was significantly greater in PV-/- than in PV+/+ animals. Extracellular single-unit activity recorded from over 1000 neurons in vivo in the temporal cortex revealed an increase of units firing regularly and a decrease of cells firing in bursts. In the hippocampus, PV deficiency facilitated the GABA(A)ergic current reversal induced by high-frequency stimulation, a mechanism implied in the generation of epileptic activity. We postulate that PV plays a key role in the regulation of local inhibitory effects exerted by GABAergic interneurons on pyramidal neurons. Through an increase in inhibition, the absence of PV facilitates synchronous activity in the cortex and facilitates hypersynchrony through the depolarizing action of GABA in the hippocampus.

Neural Network Studies. 2. Variable Selection

Quantitative structure-activity relationship (QSAR) studies usually require an estimation of the relevance of a very large set of initial variables. Determination of the most important variables allows theoretically a better generalization by all pattern recognition methods. This study introduces and investigates five pruning algorithms designed to estimate the importance of input variables in feed-forward artificial neural network trained by back propagation algorithm (ANN) applications and to prune nonrelevant ones in a statistically reliable way. The analyzed algorithms performed similar variable estimations for simulated data sets, but differences were detected for real QSAR examples. Improvement of ANN prediction ability was shown after the pruning of redundant input variables. The statistical coefficients computed by ANNs for QSAR examples were better than those of multiple linear regression. Restrictions of the proposed algorithms and the potential use of ANNs are discussed.

Neural Network Studies. 3. Variable Selection in the Cascade-Correlation Learning Architecture

Pruning methods for feed-forward artificial neural networks trained by the cascade-correlation learning algorithm are proposed. The cascade-correlation algorithm starts with a small network and dynamically adds new nodes until the analyzed problem has been solved. This feature of the algorithm removes the requirement to predefine the architecture of the neural network prior to network training. The developed pruning methods are used to estimate the importance of large sets of initial variables for quantitative structure−activity relationship studies and simulated data sets. The calculated results are compared with the performance of fixed-size back-propagation neural networks and multiple regression analysis and are carefully validated using different training/test set protocols, such as leave-one-out and full cross-validation procedures. The results suggest that the pruning methods can be successfully used to optimize the set of variables for the cascade-correlation learning algorithm neural networks. Th...

Different tonic regulation of neuronal activity in the rat dorsal raphe and medial prefrontal cortex via 5-HT1A receptors

It has been established that 5-HT(1A) receptors are expressed both presynaptically as autoreceptors by 5-HT containing neurones, and postsynaptically by a variety of other neurones. Activation of either somatodendritic 5-HT(1A) autoreceptors or postsynaptic 5-HT(1A) receptors induces hyperpolarisation and inhibition of action potential discharge of the neurones, but it is unclear whether 5-HT(1A) receptors are under a general tonic influence by 5-HT. In the present study, using single unit recordings from both anesthetized and non-anesthetized rats, we show that the activity of neurones in the medial prefrontal cortex is not altered by systemic administration of the selective 5-HT(1A) receptor antagonist, WAY 100635. In contrast, WAY 100635 increased the firing rate of 5-HT neurones in the dorsal raphe nucleus. Our findings indicate a tonic activation of presynaptic somatodendritic but not postsynaptic cortical 5-HT(1A) receptors.

Dopamine modulation of activity of cat sensorimotor cortex neurons during conditioned reflexes

The effects of iontophoretic application of dopamine and selective D1 or D2 dopamine receptor agonists and antagonists on impulse activity of neurons of the deep layers of the sensorimotor cortex of cat were investigated during performance of a conditioned paw movement task. The application of dopamine, Quinpirole (selective D2 receptor agonist) or SKF 38393 (selective D1 receptor agonist) increased both background (P<0.001) and evoked impulse activity (P<0.05 for selective agonists). Selective D2 and D1 receptor antagonists (Sulpiride and SKF 83566, respectively) both increased the latency of neural responses and significantly increased the latency of the conditioned paw movements (P<0.01). These data suggest that during natural physiological functions subcortical dopamine neurons provide facilitation of activity pyramidal neurons of sensorimotor cortex.

Neurophysiological and Psychophysiological Effects of Sulpiride in the Norm and in Patients with Opiate Addiction

We studied characteristics of the EEG activity and psychophysiological indices in healthy persons and patients with opiate addiction (in the states of abstinence and remission) before and after peroral introduction of 200 mg sulpiride. In the initial state, spectral characteristics of EEG in patients with opiate addiction differed from those in the control (in healthy tested subjects) by higher relative powers of low- and high-frequency components (delta and beta waves) and a considerable depression of the alpha rhythm. Treatment with sulpiride evoked changes in the spectral characteristics of EEG, which showed a significant intergroup specificity; intensification of alpha oscillations was a general effect in all groups. We conclude that the effects of sulpiride on the EEG activity comprised components typical of both neuroleptics and antidepressants; in the group of patients in the abstinence state, the pattern of effects of sulpiride was close in its profile to the effect of anxiolytics. Dynamics of the indices of psychophysiological testing after sulpiride treatment demonstrated that the drug exerts mostly positive regulating effects on the state of higher nervous functions in patients with opiate addiction.