From cybernetics to brain theory,and more: A memoir

While structured as an autobiography, this memoir exemplifies ways in which classic contributions to cybernetics (e.g., by Wiener, McCulloch & Pitts, and von Neumann) have fed into a diversity of current research areas, including the mathematical theory of systems and computation, artificial intelligence and robotics, computational neuroscience, linguistics, and cognitive science. The challenges of brain theory receive special emphasis. Action-oriented perception and schema theory complement neural network modeling in analyzing cerebral cortex, cerebellum, hippocampus, and basal ganglia. Comparative studies of frog, rat, monkey, ape and human not only deepen insights into the human brain but also ground an EvoDevoSocio view of “how the brain got language.” The rapprochement between neuroscience and architecture provides a recent challenge. The essay also assesses some of the social and theological implications of this broad perspective.     

Differential contributions of dorsal vs. ventral hippocampus to auditory trace fear conditioning

The effect of excitotoxic lesions of dorsal vs. ventral hippocampus on the acquisition and expression of auditory trace fear conditioning was examined in two studies. In Experiment 1, animals received excitotoxic lesions of either the dorsal or ventral hippocampus or sham surgeries one week prior to conditioning, and were tested 24 h later. In Experiment 2, animals received excitotoxic lesions of either the dorsal or ventral hippocampus or sham surgeries 24 h after training, and were tested one week after surgery. Both pre- and post-training lesions of ventral hippocampus impaired the acquisition and expression, respectively, of auditory trace fear conditioning. Pre-training lesions of dorsal hippocampus had no effect on the acquisition of trace fear conditioning, while post-training lesions of dorsal hippocampus dramatically impaired expression during subsequent testing. Although in some cases animals with lesions of ventral hippocampus exhibited locomotor hyperactivity, it is unlikely that the pattern of observed deficits can be attributed to this effect. Collectively these data suggest that the dorsal and ventral hippocampus may contribute differentially to the mnemonic processes underlying fear trace conditioning.     

Post-training, but not post-reactivation, administration of amphetamine and anisomycin modulates Pavlovian conditioned approach

The psychostimulant, amphetamine (AMPH), and the protein synthesis inhibitor, anisomycin (ANI), have been shown to modulate the consolidation and reconsolidation of several types of learning. To determine whether Pavlovian conditioned approach (PCA) is modulated in a similar manner, we examined the effects of post-training and post-reactivation administration of both AMPH and ANI on memory for PCA. Male Long-Evans rats received PCA training sessions during which presentations of a CS+ were followed by sucrose delivery. AMPH (1 mg/kg, s.c.) injected immediately but not 6h after the first training session enhanced PCA behavior. ANI (150 mg/kg, s.c.) injected immediately but not 3h after the first training session impaired PCA behavior. This impairment was not due to the development of a conditioned taste aversion. To examine whether PCA can also be modulated by post-reactivation administration of AMPH and ANI, rats were given an injection of AMPH, ANI, or vehicle immediately after a memory reactivation session. Upon testing, the behavior of both the AMPH- and the ANI-treated rats was unaffected. This result remained consistent when the experiment was repeated with changes to various behavioral parameters (i.e., amount of training, length of memory reactivation). These findings indicate that AMPH and ANI act during the post-training but not the post-reactivation period to enhance and impair, respectively, the learning of PCA. This suggests that the consolidation of PCA can be modulated in a manner comparable to other types of learned associations, but once learned, the memory appears to be relatively robust and stable.     

Making the sour sweet? Upcoming food-pellet reinforcement produces positive induction when rats press a lever for unsweetened lemon juice

Research has suggested that rats increase their response rate for a low-valued reinforcer when a high-valued reinforcer will soon be available (i.e., positive induction) because the value of the low-valued substance has increased. The present study tested if such a procedure could be used to increase rats’ responding for a non-reinforcing food. Rats pressed a lever for unsweetened lemon juice in the first half of a 50-min session and, in treatment conditions, for food pellets in the second half. Experiment 1 demonstrated that rates of responding for the lemon juice generally varied directly with the upcoming rate of food-pellet reinforcement and that responding in lemon juice-only sessions did not differ significantly from that observed during extinction. Experiment 2 demonstrated that rats consumed more lemon juice following a condition in which they were displaying positive induction than following a condition in which they only responded for lemon juice. The present results are consistent with the increase in value account of positive induction. More importantly, they may indicate that certain environmental conditions can increase food-directed behavior for a non-reinforcing food, a finding which may have implications for our understanding of eating behavior and dysfunctions (e.g., overeating).     

A comparison of event-related potentials of humans and rats elicited by a serial feature-positive discrimination task

The purpose of this experiment was to compare components of the human and rat auditory event-related potential (ERP) in a serial feature-positive discrimination task. Subjects learned to respond to an auditory target stimulus when it followed a visual feature (X → A+), but to not respond when it was presented alone (A−). Upon solving the task, the N2 component, which has been suggested to reflect the activation of inhibitory processes, was temporarily more negative in response to the target on A− than on X → A+ trials in both species. However, whereas a P3 component was present in the human participants, this component was absent in the rats. In both species, the amplitude of several ERP components, including the N2, decreased in the course of training. These results are discussed in the framework of contemporary models of associative learning.     

Activation of cannabinoid CB1 receptors in the central amygdala impairs inhibitory avoidance memory consolidation via NMDA receptors

In the present study, we investigated the influence of bilateral intra-central amygdala (intra-CeA) microinjections of N-methyl-d-aspartate (NMDA) receptor agents on amnesia induced by a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA). This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that intra-CeA administration of ACPA (2 ng/rat) immediately after training decreased inhibitory avoidance (IA) memory consolidation as evidenced by a decrease in step-through latency on the test day, which was suggestive of drug-induced amnesia. Post-training intra-CeA microinjections of NMDA (0.0001, 0.001 and 0.01 μg/rat) did not affect IA memory consolidation. However co-administration of NMDA with ACPA (2 ng/rat) prevented the impairment of IA memory consolidation that was induced by ACPA. Although post-training intra-CeA administration of the NMDA receptor antagonist, d-(−)-2-amino-5-phosphonopentanoic acid (d-AP5; 0.01, 0.05 and 0.1 μg/rat) alone had no effect, its co-administration with an ineffective dose of ACPA (1 ng/rat) impaired IA memory consolidation. Post-training intra-CeA microinjection of an ineffective dose of d-AP5 (0.01 μg/rat) prevented an NMDA response to the impaired effect of ACPA. These results suggest that amnesia induced by intra-CeA administration of ACPA is at least partly mediated through an NMDA receptor mechanism in the Ce-A.     

Chronic stress impairs recall of extinction of conditioned fear

Chronic restraint stress produces retraction of apical dendrites of pyramidal neurons in medial prefrontal cortex. To begin to examine the functional significance of this dendritic reorganization, we assessed the effects of chronic restraint stress on a prefrontally mediated behavior, extinction of conditioned fear. After bar press training to obtain a baseline of activity against which to measure freezing, rats were either unstressed or stressed via placement in a plastic restrainer (3 h/day for 1 week). After an additional day of bar press training, rats underwent fear conditioning and extinction. Rats received five habituation trials to a 30-s tone (4.5 kHz, 80 db) followed by seven pairings of tone and footshock (500 ms, 0.5 mA). One hour later, rats received tone-alone extinction trials to criterion. The next day, rats received 15 additional extinction trials. Percent freezing was assessed during all phases of training. Stress did not significantly affect unconditioned responding to tone, acquisition of conditioned fear, or initial extinction, but significantly increased freezing on extinction day 2. Thus, consistent with the regressive dendritic changes seen in medial prefrontal cortex, one week of restraint stress specifically impaired recall of extinction, a pattern of deficits typical of animals with impaired medial prefrontal function.     

Altering "motivational" variables alters induction produced by upcoming food-pellet reinforcement

Previous research has demonstrated that rats will increase their rates of lever pressing for sucrose rewards in the first half of an experimental session when food pellets, rather than the same sucrose, continually serve as the reward in the second half of the session. This effect has been coined induction, and the present study investigated whether it could be altered by altering "motivational" variables. Experiment 1 manipulated subjects' motivation by altering, across conditions, their level of food deprivation. Predictably, the size of induction varied directly with level of deprivation. Experiments 2 and 3 manipulated subjects' motivation by feeding them food pellets and sucrose, respectively, prior to their responding in the experimental session. These pre-session feedings decreased the size of the observed induction in both experiments. The results from the present study indicate that the size of induction is correlated with subjects' motivation to respond for the available reinforcers. They are also consistent with the idea that operant processes underlie the effect. The notion that induction might encompass the concept of "anticipation" is also discussed. Electronic Publication     

Three factors that promote positive induction when rats respond for 1% sucrose

Studies have demonstrated that rats will increase their operant rate of response for a low-valued reinforcer if a high-valued reinforcer will be available later in the session. Research on this positive induction effect suggests that at least three factors account for its appearance: premature responding for the yet unavailable high-valued reinforcer, an increase in the reinforcing value of the low-valued reinforcer, and responding controlled (e.g., elicited) by the response manipulandum. The present experiment tested whether the size of induction could be systematically altered by varying these factors. Twenty-four rats responded in sessions in which 1% sucrose or a food pellet served as the reinforcer in the first or second half of the session. In some sessions, the same operant response was required in both halves of the session. In others, different responses were required. Half of the rats received the different reinforcers in one food trough while the other half received reinforcers in the different halves of the session in different food troughs. Results demonstrated that a large positive induction effect was observed when all of the above factors were present to contribute to the effect (i.e., high-valued reinforcer upcoming, earned by making the same response, delivered to the same food trough). A small, but significant, induction effect remained when all three were absent (i.e., high-valued reinforcer delivered first, earned by making a different response, delivered to a different food trough). The results support the idea that these three factors are the main contributors to the appearance of this positive induction effect. However, at least one additional factor must also contribute.     

Transfer of old ‘reactivated’ memory retrieval cues in rats

The present studies examined whether the retrieval of an old ‘reactivated’ memory could be brought under the control of new contextual cues. In Experiment 1 rats trained in one context were exposed to different contextual cues either immediately, 60 or 120 min after a cued reactivation of the training memory. When tested in the shifted context, subjects exposed shortly after reactivation treated the shifted context as the original context. This transfer diminished with longer post-reactivation delays. Experiment 2 replicated the basic finding and demonstrated that the transfer of the old retrieval cues was specific to the contextual cues present during exposure. These findings are consistent with previous research [i.e., Briggs, J. F., Fitz, K. I., & Riccio, D. C. (in press). Transfer of memory retrieval cues in rats. Psychonomic Bulletin & Review] showing the transfer of retrieval cues for a new memory, and demonstrating a similarity (in this case) between newly acquired and old reactivated memories.