David G. Spencer

Parallel processing strategies in the application of microcomputers to the behavioral laboratory

The Operant Package for the Neurosciences (OPN) is a software system that runs on the TRS-80 Model I and Model III and the Apple II+ and Apple lie microcomputers. It is designed to allow a single microcomputer to control behavioral experiments in up to eight different stations, record experimental data, and provide detailed data analysis. Although segments of the program are written in BASIC, allowing users to interact with OPN in a simple English question-and-answer format, the part that provides real-time experimental control is written in Z-80 assembly language. The present report describes in detail assembly language algorithms that we found to facilitate speed of processing and flexibility of control. Particular problems dealt with how to update and change flag variables controlling the reinforcement contingencies and output conditions in each station, as well as how to decide when each station should shift contingencies. The solutions to these problems utilize byte-oriented parallel processing strategies, converting serially organized reference information for each station into a group of working flag bytes that control contingency and output variables for all stations in parallel.

Central cholinergic involvement in working memory: Effects of scopolamine on continuous nonmatching and discrimination performance in the rat.

Rats were trained to stable baselines of lever pressing on a variable intertrial interval continuous nonmatching to sample schedule (CNM) or on an analogous discrimination schedule. Scopolamine reduced accuracy of CNM performance to a similar extent over the three intertrial (retention) intervals: 2.5, 5, and 10 s, results indicating that the drug did not affect the time-dependent process of retention in working memory. When baseline levels of performance accuracy were similar in the CNM and discrimination tasks (but stimulus discriminability was greater in the CNM task), scopolamine reduced accuracy equally in the two procedures. Effects of scopolamine on accuracy of noncorrection trial CNM performance were simulated by reducing stimulus discriminability; however, scopolamine disrupted CNM correction trial performance much more than did reductions in stimulus discriminability. It is concluded that scopolamines effects on working memory are not limited to possible effects on stimulus discrimination: Scopolamine may also affect retrieval of response rules from reference memory.

Behavioral impairments related to cognitive dysfunction in the autoimmune New Zealand black mouse.

The possibility that autoimmunological disorders involving neuronal constituents as autoantigens can result in measurable behavioral impairments prompted the behavioral analysis of the New Zealand black (NZB) mouse strain, known to have high levels of brain-reactive antibodies. Sensorimotor competence and performance in tasks requiring learning and memory were assessed in 7-10-month-old NZB and contrasted with those of CFW mice. The NZB mice showed pronounced deficits in performance of passive and active shock avoidance responses. These deficits could not be accounted for by the slight sensorimotor disadvantage of NZB mice relative to CFW mice. No difference between the two mouse strains was seen in passive avoidance behavior at 1.5 months of age. It is concluded that NZB mice display a behavioral deficit related to cognitive dysfunction and that autoimmune mechanisms may be involved in the etiology of this deficit. Such behavioral disturbances produced by an autoimmune mechanism may have relevance for the neurological declines observed in aging, since the incidence of autoimmune disorders increases markedly in old age.

Anxiogenic aspects of diazepam withdrawal can be detected in animals

Animals can be trained to discriminate the presence of pentylenetetrazol, and this discrimination has previously been proposed as an animal bioassay for anxiogenicity. In rats made dependent on diazepam, pentylenetetrazol-like stimuli occurred during spontaneous or precipitated (with RO 15-1788) withdrawal; these stimuli were blocked by pentobarbital. These results demonstrate that the pentylenetetrazol-based animal model of anxiety can be used to objectively quantify a subjective aspect of benzodiazepine dependence/withdrawal.

Task-specific tolerance to d-amphetamine.

Rats were trained concurrently on sweetened-milk drinking and bar-press-responding behavior, which alternated on a daily basis. Dose-response functions for d-amphetamine were determined before and after conditions of chronic treatment. When given before chronic treatment, d-amphetamine decreased both milk consumption and reinforcement received for lever-pressing in a dose-dependent manner. Subsequently, three conditions of chronic injection were established in which one group received saline, prior to both tasks, another group received d-amphetamine prior to drinking milk and saline prior to lever-pressing and the third group received d-amphetamine prior to lever-pressing and saline before drinking milk. The rats became tolerant to d-amphetamine in the task in which the drug had been administered chronically; however, the same rats showed no tolerance in the other task in which saline had been administered chronically. Tolerance to d-amphetamine was thus shown to be behaviorally specific.

Behavioral and physiological detection of classically-conditioned blood pressure reduction

Spontaneously hypertensive (SH) rats were trained to discriminate the effects of saline injection from the interoceptive stimuli associated with the blood-pressure-reducing effect of clonidine (0.02 mg/kg, IP) in a drug discrimination procedure. Anise/ethanol and ethanol odors were then systematically paired with clonidine and saline treatment, respectively, outside the drug discrimination setting. As the number of pairings increased, the anise/ethanol (but not the ethanol) stimulus, when given alone, came to both reduce blood pressure and to mimic clonidines interoceptive stimulus to virtually the same extent as clonidine itself. Both responses induced by the conditioned stimulus (CS+; anise/ethanol odor) were antagonized by the noradrenergic alpha-2 receptor antagonist yohimbine at a dose that did not by itself influence blood pressure. These data support the hypothesis that activation of endogenous factors can be elicited by a CS, and that these factors may furthermore act agonistically at central alpha-2 receptors to reduce blood pressure in hypertensive animals.

Central Cholinergic Involvement in Learning and Memory

Drugs affecting cholinergic transmission in the brain have long been known to disrupt learned behaviors in rather specific ways. Several different theoretical formulations of cholinergic function have been developed focusing primarily on concepts such as behavioral inhibition (Carlton, 1963), discrimination (Milar et al., 1978), learning (Deutsch, 1973), and memory (Bartus and Johnson, 1976). Their differences seem to be due to differential emphasis on various groups of experimental findings. In this review, we will examine several experiments using cholinergic drugs to produce changes in learning and/or memory performance, with the goal of generating a hypothesis of central cholinergic function in cognitive processing. In so doing, our discussion will be largely focused on the effects of muscarinic receptor antagonists for two reasons. First, the vast majority of acetylcholine (ACh) receptors in the mammalian brain are of the muscarinic type. The predominance of muscarinic receptors is also apparent in brain structures that seem specifically involved with attentional, acquisitional, or memorial function, such as the hippo-campus. Second, the effects of systemic muscarinic blockade on performance in memory tasks are much more striking than those of nicotinic stimulation or blockade. The discussion will also be limited to cholinergic drug effects on behaviors requiring learning and/or memory since it is clear that cholinergic transmission also participates in sensory processing (the auditory pathway), motor function (the extrapyramidal motor system), and the alerting response, for example. The implicit assumption is therefore that in focusing on learning and memory performance, drug effects on the subset of cholinergic circuits dealing with such cognitive processes will predominate.