Participation of the dorsal hippocampus in stimulus discrimination with scopolamine.

Stimulus discrimination is the capacity of an organism to differentiate between stimuli and emit associated responses. The administration of the muscarinic antagonist scopolamine can be used as a stimulus by mammals in a discrimination task. The present study analyzes the contribution of the hippocampus in scopolamine discrimination and generalization. Male Wistar rats, weighing 250-300 g at the beginning of the experiment, were trained to discriminate between scopolamine (1.0 mg/kg, i.p.) and saline administration using a two-lever operant task; rats had to respond differentially to each lever depending on the preceding drug or saline administration. Once stimulus control was attained, rats were tested with different scopolamine doses (0.0, 0.056, 0.091, 0.16, 0.31 and 1.0 mg/kg, i.p.) in order to obtain generalization curves. After generalization the rats were randomly assigned to hippocampal CA1 lesion or control groups. Hippocampus impairment produced a transient decrease in the capacity to discriminate between scopolamine and saline conditions; nonetheless, scopolamine correct responses were rapidly recovered after a few sessions and even maintained after 90 days. Correct responses for saline condition were never recovered. The generalization curve obtained after hippocampus lesion showed a response gradient severely flattened. Results suggest that the hippocampus participates as a neural system supporting the sensitivity to detect discrete changes in stimulus properties and relational memory, more than on the capacity to recall for simple associative responses.

Roles of ryanodine and inositol triphosphate receptors in regulation of plateau potentials in turtle spinal motoneurons.

Generation of plateau potentials in spinal motoneurons depends on activation of voltage sensitive L-type Ca(2+) channels. These channels are facilitated by metabotropic receptors known to promote release of Ca(2+) from intracellular stores. The aim of this study is to determine if Ca(2+)-release receptors in the endoplasmic reticulum (ER) that are sensitive to ryanodine (RyRs) and to inositol triphosphate receptors (IP(3)Rs) contribute to the generation of plateau potentials. The effects of antagonists to RyRs, IP(3)Rs and phospholipase C (PLC) were tested on discharge patterns associated with plateau potentials in motoneurons in slices from the spinal cord of the turtle. Plateau-related discharge patterns, un-facilitated or facilitated by agonists for group I glutamate metabotropic receptors, muscarine-sensitive cholinergic receptors or L-type Ca(2+) channels were inhibited by blockade of RyRs. In contrast, antagonists of IP(3)Rs or PLC preferentially inhibited plateau-related discharge patterns when facilitated by activation of metabotropic receptors but in only half of the cells when promoted in the absence of metabotropic facilitators. Our findings show that RyRs and IP(3)Rs regulate the generation of plateau potentials in motoneurons and suggest that RyRs may be directly involved with activation of the plateau potential.

Facilitation of plateau potentials in turtle motoneurones by a pathway dependent on calcium and calmodulin.

1. The involvement of intracellular calcium and calmodulin in the modulation of plateau potentials in motoneurones was investigated using intracellular recordings from a spinal cord slice preparation. 2. Chelation of intracellular calcium with BAPTA-AM or inactivation of calmodulin with W-7 or trifluoperazine reduced the amplitude of depolarization-induced plateau potentials. Inactivation of calmodulin also inhibited facilitation of plateau potentials by activation of group I metabotropic glutamate receptors or muscarinic receptors. 3. In low-sodium medium and in the presence of tetraethylammonium and tetrodotoxin, calcium action potentials evoked by depolarization were followed by a short hyperpolarization ascribed to the calcium-activated non-selective cationic current (ICAN) and by a dihydropyridine-sensitive afterdepolarization. The amplitude of the afterdepolarization depended on the number of calcium spikes and was mediated by L-type calcium channels. 4. The dihydropyridine-sensitive afterdepolarization induced by calcium spikes was reduced by blockade of calmodulin. 5. It is proposed that plateau potentials in spinal motoneurones are facilitated by activation of a calcium-calmodulin-dependent pathway.