Enhancement of the Post-training Cholinergic Tone Antagonizes the Impairment of Retention Induced by a Nitric Oxide Synthase Inhibitor in Mice

The present experiments examined the role of the central cholinergic system in the memory impairment induced by post-training administration of a nitric oxide synthase (NOS) inhibitor in mice. Male Swiss mice received a one-trial inhibitory avoidance training (0.8 mA, 50 Hz, 1-s footshock) followed immediately by an ip injection of the NOS inhibitor -N^G-nitroarginine methyl ester ( -NAME; 100 mg/kg). Retention (cut-off time, 300 s) was tested 48 h after training. The administration of -NAME results in memory impairment for the inhibitory avoidance task. The effects of -NAME (100 mg/kg, ip) on retention were reversed in a dose-related manner by the centrally acting anticholinesterase physostigmine (35, 70, or 150 μg/kg, sc) administered 30 min after the NOS inhibitor. Further, -NAME (100 mg/kg, ip)-induced memory impairment was completely antagonized by the centrally acting muscarinic cholinergic agonist oxotremorine (OTM; 25, 50, or 100 μg/kg, sc) when given 30 min after -NAME. The peripherally acting anticholinesterase neostigmine (150 μg/kg, sc) did not modify the memory-impairing effects of -NAME. These findings suggest that the memory impairment following post-training administration of a NOS inhibitor is mediated, at least in part, by a reduction of the activity of central muscarinic cholinergic mechanisms and are consistent with our previous view that nitric oxide may be involved in post-training neural processes underlying the storage of newly acquired information.     

Effects of Posttraining Administration of Glucose on Retention of a Habituation Response in Mice: Participation of a Central Cholinergic Mechanism

Male Swiss mice were allowed to explore a novel environment, provided by an open-field activity chamber, for 10 min. The procedure was repeated twice with a 24-h interval. The difference in the exploratory activity between the first (training) and the second (testing) exposures to the chamber was taken as an index of retention of this habituation task. Posttraining intraperitoneal administration of glucose (10–300 mg/kg) enhanced retention in a dose-related manner, although only the dose of 30 mg/kg of glucose produced significant effects. Thus, the dose–response curve adopted an inverted U-shaped form. Glucose (30 mg/kg) given to untrained mice did not modify their exploratory performance when recorded 24 h later. The effects of glucose on retention were time-dependent, suggesting an action on memory storage. The memory-improving actions of glucose were prevented by the simultaneous administration of both the central acting muscarinic cholinergic antagonist atropine (0.5 mg/kg) and by the central acting nicotinic cholinergic antagonist mecamylamine (5 mg/kg). In contrast, neither methylatropine (0.5 mg/kg), a peripherally acting muscarinic receptor blocker, nor hexamethonium (5 mg/kg), a peripherally acting nicotinic receptor blocker, prevented the effects of glucose on retention. Low subeffective doses of glucose (10 mg/kg) and the central anticholinesterase physostigmine (35 μg/kg), but not neostigmine (35 μg/kg), given together, act synergistically and facilitated retention. We suggest that glucose modulates memory storage of one form of learning elicited by stimuli repeatedly presented without reinforcement, probably through an enhancement of brain acetylcholine synthesis and/or its release.     

Sentence processing: Evidence against the serial,independent stage assumption

The assumption that the processing stages involved in sentence comprehension are serially and independently executed was tested in two separate experiments using two new sentence types. One experiment was a sentence-picture verification task, the other was not. In Experiment I, subjects viewed sentences such as It's false that the dots are red and indicated, by pressing the appropriate response key, which of two colors would make the sentence true. In Experiment II, subjects verified sentences such as It isn't true that the dots aren't red against pictures of colored dots. On the strength of Sternberg's additive factor method, present findings challenge the validity of the serial, independent stage assumption, and results are alternatively discussed in terms of a capacity sharing model.This research was supported by PHS research grant MH 23401 to Sam Glucksberg, principal investigator.     

Forest lights: Notes on the conceptualization of the unconscious

Using the metaphor of lights appearing unexplained in the night, the author argues for a conceptualization of the unconscious based on a posture of trust and acceptance rather than one of fear and explanation.His last book,Idea and Experience, dealt with Husserl's project of phenomenology inIdeas I. He has recently completed another book,The Embers and the Stars: A Philosophical Inquiry into the Moral Sense of Nature.     

Zur Geschichte und gegenwärtigen Lage der Philosophie in der ČSR

Official Czech philosophy has been dominated by a mix of Engelsian philosophy of science and positivism, a combination explained in part by the survival of positivism in Czechoslovakia and the failure of analytic philosophy to make inroads into Czech thinking. However, due to Jan Patoka's influence in espousing the works of Husserl and Heidegger, there was an anthropologically oriented Marxism (K. Kosik) although its successes were greater abroad than in Czechoslovakia. A more neopositivistic variant (L. Tondl) of Marxism also appeared, but it was a short-lived phenomenon without purchase on mainstream philosophy.A certain renewal of Czech philosophy was evident before 1968, once again largely due to Patoka's influence. Foreign guests who took part in informally organized, often secret, seminars and discussion groups were very instrumental in spreading new ideas. Despite these positive occurrences, Czech philosophy is experiencing a crisis at the level of the middle generation of non-academic, philosophically competent intellectuals among whom sceptical and nihilist attitudes prevail. A rebirth of spirit may be in the offing if the recovery of the specific sense of the Czech Reformation's idea of truth is pursued.     

Sensorimotor synchronization: Motor responses to regular auditory patterns

Subjects (N = 32) were asked to synchronize a motor response with tones in auditory patterns. These patterns were created from six tones and six intertone intervals of equal duration. The pitch of the first tone differed from the others. It was found that subjects used three types of timing in their motor response: (1) the first intertone interval was prolonged and the second interval was shortened, (2) the second intertone interval was prolonged and the first interval was shortened, and/or (3) the first interval and the second interval were of approximately the same length. The prolongation of the fifth interval was observed during all three types of timing. The results are explained using the concept of suprasegmental control of timing, which explains a prolongation of intervals at critical control point of the patterns. The occurrence of three different strategies of timing is discussed in connection with similar principles in musical performance.