Extinguished operant responding shows stimulus specificity

The experiment tested for stimulus specificity in extinguished operant responding. Eight pigeons pecked keys for food reinforcers delivered by a variable interval (VI) 60-s schedule. The key was illuminated with red light during some sessions and white light during others. Then, responding was placed on extinction. During some sessions of extinction, the color of the key light remained constant throughout the session (red or white). During other sessions the color changed at 30 min into the session (red to white or white to red). Response rate increased after the change of key color in extinction. If it is assumed that key color is part of the stimulus to which subjects habituate, then these results are consistent with McSweeney and Swindell's [J. Gen. Psychol. 129 (2002) 364] suggestion that responding declines in extinction partly because subjects habituate to the stimuli that support conditioned responding. Habituation is relatively specific to the exact nature of the stimulus presented. Therefore, changes in the stimulus violate stimulus specificity and restore habituated responding. The results are also consistent with other theories that attribute extinction to a reduction of stimulus control [e.g., Psychol. Bull. 114 (1993) 80; J. Exp. Psychol.: Anim. Behav. Process. 16 (1990) 235], but considerations such as parsimony and testability favor the habituation hypothesis over these theories.     

Testing for episodic-like memory in rats in the absence of time of day cues: replication of Babb and Crystal

Two experiments were performed to look for evidence of episodic-like memory in rats. On each of a series of trials on an eight-arm radial maze, rats in two groups entered four open arms in Phase 1, with reward pellets on three arms and a favored reward (chocolate in Experiment 1 and cheese in Experiment 2) on the remaining arm. Phase 2 retention tests were given 30 min or 4 h after Phase 1, with all eight arms open. The four arms not entered in Phase 1 all contained reward pellets, and the three arms that contained pellets in Phase 1 were empty. In the replenish short group, the favored reward was replenished at the same location where it was found in Phase 1 at the 30 min retention interval but was absent (Experiment 1) or degraded (Experiment 2) at the 4 h retention interval. In the replenish long group, the favored reward was replenished at the 4 h retention interval but not at the 30 min retention interval. Over a number of daily trials that randomly mixed short and long delays, rats in both experiments learned to return earlier to the arm containing the favored reward at the retention interval when it was replenished than at the retention interval when it was absent or degraded. These results replicate earlier findings [Babb, S.J., Crystal, J.D., 2005, Discrimination of what, when, and where: implications for episodic-like memory in rats. Learn. Mot., 36, 177-189] and provide evidence of episodic-like memory in rats.     

Timing of omitted events: an analysis of temporal control of inhibitory behavior

This paper reviews research designed to investigate the temporal control of inhibitory responding using rats as subjects. One area of investigation has focused on the role of temporal variables in conditioned inhibition produced using Pavlov's [Pavlov, I.P., 1927. Conditioned Reflexes. Oxford University Press, London, 430 pp.] procedure. These studies have found that evidence of conditioned inhibition obtained by negative summation testing is strongest when the conditioned inhibitor signals the omission of the unconditioned stimulus (US) at the same temporal location as a transfer excitor signals presentation of the US [e.g., Barnet, R.C., Miller, R.R., 1996. Temporal encoding as a determinant of inhibitory control. Learn. Motiv. 27, 73-91]. Similarly, retardation of acquisition of behavioral control by a previously inhibitory conditioned stimulus (CS) is maximal when the inhibitory CS is paired with the US at the same temporal location as the inhibitor had previously signaled US omission [Burger, D., Denniston, J.C., Miller, R.R., 2001. Temporal coding in condition inhibition: retardation tests. Anim. Learn. Behav. 29, 281-290]. Other lines of research designed to assess the associative structure of temporal control of inhibition [e.g., Denniston, J.C., Blaisdell, A.P., Miller, R.R., 2004. Temporal control in conditioned inhibition: analysis of associative structure of inhibition. J. Exp. Psychol. Anim. Behav. Process. 30, 190-202] are reviewed, as is the assessment of temporal control of inhibition produced through extinction [Denniston, J.C., Miller, R.R., 2003. The role of temporal variables in inhibition produced through extinction. Learn. Behav. 31, 35-48]. These collective observations are discussed in terms of the temporal coding hypothesis [Matzel, L.D., Held, F.P., Miller, R.R., 1988. Reexamination of simultaneous and backward conditioning: Implications for contiguity theory. Learn. Motiv. 19, 317-344].     

The influence of comparison between similar stimuli on the effectiveness of their unique features

Four groups of rats received stimulus pre-exposure under conditions intended to produce different opportunities for stimulus comparison to occur. Groups AX/BX-L and AX/BX-S received alternating presentations of two compound flavors (AX and BX); the interval between these presentations was long (24 h) for group AX/BX-L, and short (5 min) for group AX/BX-S. Groups AX-L and AX-S matched groups AX/BX-L and AX/BX-S in their pre-exposure conditions except that they received presentations of water rather than presentations of BX. The effective salience of one of the unique stimulus features (A) was then assessed by using this flavor as a conditioned stimulus in a flavor-aversion procedure. It was found that aversion to A was learned about more readily after pre-exposure to AX and BX than after pre-exposure just to AX. However, there was no indication that the rate of conditioning to A was affected by the temporal interval between the presentations of AX and BX. These findings challenge the notion that stimulus comparison engages a process responsible for an increase in the salience of the unique stimulus features, but can be accommodated by the salience modulation mechanism proposed by Hall [Hall, G., 2003. Learned changes in the sensitivity of stimulus representations: associative and nonassociative mechanisms. Q. J. Exp. Psychol. 56, 43-55].     

Retroactive interference after discrimination reversal decreases following temporal and physical context changes in human subjects

One experiment was conducted to test the additive effects of physical context changes and the passage of time on a retroactive interference task in human subjects. Participants learned a discrimination in a symbolic matching to sample situation within a specific context. The discrimination was subsequently reversed. The context in which the reversal occurred was combined factorially with the passage of time before the test. All testing was conducted in the context in which the original discrimination was acquired. Participants had received the discrimination reversal in either a context different from that in which the original discrimination was acquired, or in the same context. Half of each of the groups mentioned above received testing immediately after reversal training and the other half received testing 48 h later. Both manipulations, changing the context after the reversal and the passage of time following the reversal, led to a recovery of the original discrimination performance. Participants that received both a context change and retention interval showed the largest recovery.     

Sensitivity to initial conditions in the route-finder model

A model of stimulus generalization [Staddon, J.E.R., Reid, A.K., 1990. On the dynamics of generalization. Psychol. Rev. 97, 576-578] was extended by Reid and Staddon [Reid, A.K., Staddon, J.E.R., 1998. A dynamic route finder for the cognitive map. Psychol. Rev. 105, 585-601] to account for the route-finder issue in the Tolman-Guthrie discussion about cognitive maps. This deterministic model has been described as sensitive to initial conditions in terms of the parameters of a diffusion equation [Reid, A.K., Staddon, J.E.R., 1998. A dynamic route finder for the cognitive map. Psychol. Rev. 105, 585-601]. A simulation study was carried out to test this assertion, evaluating whether the pattern of variation in the model output resembled a chaotic pattern. Results indicate that the model is sensitive to initial conditions, suggesting that the spatial navigation task addressed by this model involves non-linear relationships and complexity beyond the apparent simplicity of the stimulus generalization process.     

Demonstration of dissociation between frontal and temporal lesions in man on two versions of delayed non-matching recognition tests used in monkeys]

11 patients with frontal lobe lesions (F group), 9 patients with temporal lobe lesions (T group) and 18 normal control subjects (C group) were tested on two versions of the delayed non matching-to-sample task using either different pairs (DNMTS) or the same pairs of objects (RECURRENT) on successive test trials. The results revealed that the DNMTS task was sensitive to memory impairment but did not differentiate the two experimental groups. In contrast, the recurrent version of the task showed a dissociation between the two pathologies. Thus, whereas patients of group T exhibited an accelerated rate of forgetting as a function of the retention interval, patients of group F were impaired whatever the retention interval.     

The temporal pattern of responding in conditioned bar-press suppression: the role of the context switch and training mode

The present study examined the temporal pattern of responding in a conditioned bar-press suppression task in rats. Rats were exposed to either a 30-s or a 120-s conditioned stimulus (CS) followed by a footshock. Training took place either while the rats were lever-pressing for water (online), or with the lever removed from the box (offline). They were then exposed to the CS while they were lever-pressing for water, either in the training context or in a different context. Bar-press suppression during the CS was constant across the duration of the CS during training, but was restricted to the initial portion of the CS at the time of testing, especially when subjects were tested in a different context. Those results replicate the reactive (as opposed to anticipatory) pattern observed in a lick suppression procedure by Jozefowiez et al. (2011) and indicate that a change in context at the time of testing might be critical for its expression.     

Blocked and test-stimulus exposure effects in perceptual learning re-examined

Three experiments re-examined the effects of blocked or alternated exposure to the conditioning and test stimuli and the effect of simple exposure to the test stimulus, on stimulus generalization. In all experiments rats received conditioning where a compound flavor, AX, was paired with LiCl-induced illness. All rats were tested for generalization with another flavor, BX. In Experiment 1, rats that received alternating exposure to the two flavor compounds, AX and BX, prior to conditioning showed less generalization to BX than rats that received no exposure. Exposure to BX or AX alone was also somewhat effective in reducing generalization. In Experiment 2 blocked exposure to AX and BX prior to conditioning was effective in reducing generalization, as was alternated exposure, and extended exposure to BX was more effective than the other procedures. In Experiment 3, exposure to X alone prior to conditioning produced generalization equal to that produced by alternated or blocked exposure and replicated the effect of extended exposure to BX found in the previous experiment. The relevance of the results to the theories proposed by McLaren and Macintosh [Anim. Learn. Behav. 28 (2000) 211] and Hall [Q. J. Exp. Psychol. B 56 (2003) 43] is discussed.     

Effects of thyroid states on the Cori cycle,glucose-alanine cycle,and futile cycling of glucose metabolism in rats

The effect of thyroid status on glucose recycling was measured in intact rats by comparing the fates of differently labeled [³H]- and [¹⁴C]glucose. Glucose recycling at the level of three-carbon compounds (i.e., Cori and glucose-alanine cycles) was measured by comparing the rates of turnover of [6-³H]- and [6-¹⁴C]glucose in the same animal. The rate of recycling increased (33–110%) in hyperthyroid rats and decreased (22–30%) in hypothyroid (thyroidectomized) rats. The relative importance of the Cori and glucose-alanine cycles was measured by analyzing the labeled glycolytic intermediates after the injection of labeled glucose; and by measuring the rate of glucose production from the infused labeled lactate and alanine. The results showed that the rate of the Cori cycle is much greater than the glucose-alanine cycle in rats. Substrate cycling at the level of glucokinase-glucose-6-phosphatase was measured by comparing the rates of turnover of [2-³H]- and [6-³H]glucose; and phosphofructokinase-fructose bisphosphatase was measured by comparing the rates of turnover of [3-³H]- and [6-³H]glucose. These cycles were also affected by thyroid states of the animals. The rate of the phosphofructokinase-fructose bisphosphatase cycle increased threefold in hyperthyroid rats and decreased by about half in hypothyroid rats. The glucokinase-glucose-6-phosphatase substrate cycle occurred at the rate of nearly 2 μmol/min/100 g body wt in the hyperthyroid, fasted rats; it was not detectable in hypo- or euthyroid rats. The contribution of the energy released by these cycles to thyroid thermogenesis was discussed. Effects of thyroid states on glucose metabolism in perfused muscles were also studied. There is an apparent shift in the source of energy for oxidation in the hyperthyroid rat. The ratio of lactate production to glucose uptake was significantly elevated in the hyperthyroid rats. This change predisposes for increased glucose recycling in hyperthyroid rats to avoid lactate accumulation and acidosis.     

Spaced initial stimulus familiarization enhances novelty preference in Long-Evans rats

Berlyne [Berlyne, D.E., 1950. Novelty and curiosity as determinants of exploratory behaviour. Brit. J. Psychol. 41, 68–80] first illustrated that rats prefer to explore novel objects over ones with which they have had previous experience. Recently, variants on this novel object recognition (NOR) task have become widely popular and have been employed in numerous neuroscience and behavioral pharmacological studies investigating memory processes. Given this popularity, a thorough understanding of the various behavioral processes involved in novelty reaction and preference is essential. The current study compared the effects of spaced and massed initial stimulus exposures upon later object exploration and novel stimulus preference in Long-Evans rats. Results illustrated that a distributed initial stimulus familiarization procedure promoted greater novel object preference than did a massed procedure, and suggest that the novel object recognition task is sensitive to spacing effects in a similar fashion to more traditional learning paradigms. The mechanisms underlying such spacing effects are briefly discussed.     

Removal of cholesteryl ester from hepatic reticuloendothelial cells in vivo is not enhanced by plasma cholesteryl ester transfer protein

The putative role of cholesteryl ester transfer protein (CETP) in the removal of cholesteryl ester from hepatic reticuloendothelial cells in vivo was studied in hamsters. The parameter tested was retention of [3H]cholesteryl linoleyl ether ([3H]CLE), a nonhydrolysable analog of cholesteryl ester, in the liver after injection of [3H]CLE labeled acetylated LDL, which is targetted to nonparenchymatous littoral cells. In hamsters fed laboratory chow, plasma cholesteryl ester transfer activity (CETA) was 10.6 +/- 0.9 units and the retention of [3H]CLE in the liver 28 days after injection was 86% of the 4 h value. It was about 55% in rats fed the same diet, in which CETA was not detectable. When the diet was supplemented with 2% cholesterol and 15% margarine, CETA activity in hamsters increased 2-fold, yet no change in retention of [3H]CLE in liver was seen after 28 days. In rats, the retention of [3H]CLE in the liver was also not changed by the dietary fat supplementation. These results do not support the role of CETP in vivo in removal of cholesteryl ester from intact reticuloendothelial cells.     

Codes, operations, measurements and neural networks

Numerous neural codes and primary neural operations (logical and arithmetical ones, mappings, transformations) were listed [e.g. Perkel, D., Bullock, T.H., 1968. Neurosci. Res. Program Bull 6, 221-348] during the past decades. None of them is ubiquitous or universal. In reality neural operations take place in continuous time and working with unreliable elements, but they still can be simulated with synchronized discrete time scales and chaotic models. Here, a possible neural mechanism, called 'measure like' code is introduced and examined. The neurons are regarded as measuring devices, dealing with 'measures', more or less in mathematical sense. The subadditivity--eminent property of measures--may be implemented with neuronal refractoriness and such synapses operate like particle counters with dead time. This hypothetical code is neither ubiquitous, nor universal, e.g. temporal summation (multiplication) causes just the opposite phenomenon, the supra-additivity also with respect to the number of spikes (anti-measures). This is a cause of more difficult neural implementation of OR gate, than that of the AND. Possibilities for transitional mechanisms (e.g. between traditional logical gates, etc.) are stressed here. Parameter tuning might change either code or operation.     

Phospholipids chiral at phosphorus. Synthesis of chiral phosphatidylcholine and stereochemistry of phospholipase D

Chirally labeled 1,2-dipalmitoyl-sn-glycero-3-phosphocholines (DPPC) with known configuration were synthesized by N-methylation of chirally labeled 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE). Transphosphatidylation of (RP)- and (SP)-[18O]DPPC catalyzed by phospholipase D from cabbage gave (RP)- and (SP)-[18O]DPPE, respectively, as indicated by 31P nuclear magnetic resonance (NMR) analysis of [18O]DPPE. Therefore, phospholipase D catalyzes transphosphatidylation with overall retention of configuration at phosphorus. The steric course of hydrolysis of DPPC catalyzed by the same enzyme was elucidated by the following procedures. Hydrolysis of (RP)-[17O, 18O]DPPC by phospholipase D gave 1,2-dipalmitoyl-sn-glycero-3-[ 16O , 17O, 18O]phosphate ( [ 16O , 17O, 18O] DPPA ) with unknown configuration. The latter compound was then converted to 1-[ 16O , 17O, 18O]phospho-(R)-propane-1,2-diol by a procedure involving no P-O bond cleavage [ Bruzik , K., & Tsai, M.-D. (1984) J. Am. Chem. Soc. 106, 747-754]. The configuration of the phosphopropane -1,2-diol was determined as RP by 31P NMR analysis following ring closure and methylation [ Buchwald , S. L., & Knowles, J. R. (1980) J. Am. Chem. Soc. 102, 6601-6603]. The results indicated that hydrolysis of DPPC catalyzed by phospholipase D also proceeds with retention of configuration at phosphorus. Our results therefore support a two-step mechanism involving a phosphatidyl-enzyme intermediate in the reactions catalyzed by phospholipase D from cabbage.     

Biochemical Evidence of Selective Nerve Cell Changes in the Normal Ageing Human and Rat Brain

Abstract: Atrophy with ageing of human whole brain, entire temporal lobe, and caudate nucleus was assessed in autopsy specimens, by biochemical techniques. Only the caudate nucleus showed changes. Markers for several neurotransmitter systems were also examined for changes with age. In neocortex and temporal lobe of human brain, small decreases were detected in markers of cholinergic nerve terminals, whereas a large decrease (79%) occurred in the caudate nucleus. Findings were similar in striatum from 3–33-month-old rats. No change occurred in binding of [³H]quinuclidinyl benzilate by human samples. Markers of serotonergic terminals were also unchanged in human and rat brain. By contrast, binding of [³H]lysergic acid diethylamide and [³H]serotonin was decreased (32–81%) in human neocortex and temporal lobe, but not in caudate nucleus. A 43% loss of a marker of γ-aminobutyrate terminals occurred in human neocortex, while [³H]muscimol binding increased (179%). No changes were detected in markers of catecholamine synapses in temporal lobe or rat striatum. Hence, with human ageing there appears to be a loss of markers of γ-aminobutyrate neurones intrinsic to neocortex and acetylcholine cells intrinsic to the caudate nucleus, as well as a change in postsynaptic serotonin receptors in neocortex. These losses are accompanied by relative preservation of markers of ascending projections from basal forebrain and brain stem.     

Repeated injection of MK801: An animal model of schizophrenia?

Glutamate-induced neurotoxicity plays an important role in neurological and psychiatric diseases. Thus, much attention has been given to the potential neuroprotective role of glutamate receptor antagonists, especially to those acting on the N-methyl-d-aspartate (NMDA) subtype. However, in addition to their neuroprotective potential, these compounds have also neurotoxic and psychotogenic properties. In the present study we used repeated injections of MK801 to examine if this non-competitive NMDA receptor antagonist could be used to produce schizophrenia-like alterations in behavior and brain metabolism in animals. Rats were given injections of MK801 (0.1 mg/kg) on six consecutive days, the last dose together with [1-(13)C]glucose and [1,2-(13)C]acetate, to probe neuronal and astrocytic metabolism, respectively. Analyses of extracts from parts of the frontal cortex plus cingulate and retrosplenial cortices and temporal lobes were performed using (13)C and (1)H magnetic resonance spectroscopy. Changes in glutamate and glutamine were restricted to the temporal lobe, in which amounts and labeling from [1-(13)C]glucose and [1,2-(13)C]acetate were increased compared to control. Locomotor activity was slightly higher in rats treated with MK801 compared to untreated animals. Metabolic changes did not resemble the alterations occurring in schizophrenia and those after repeated high dose (0.5 mg/kg) [Kondziella, D., Brenner, E., Eyjolfsson, E.M., Markinhuhta, K.R., Carlsson, M., Sonnewald, U., 2005. Glial-neuronal interactions are impaired in the schizophrenia model of repeated MK801 exposure. Neuropsychopharmacology, Epub ahead of print] but rather those caused by MK801 seen after a single high dose (0.5 mg/kg) [Brenner, E., Kondziella, D., Haberg, A., Sonnewald, U., 2005. Impaired glutamine metabolism in NMDA receptor hypofunction induced by MK801. J. Neurochem. 94, 1594-1603.].     

Rats exhibit asymmetrical retention functions for hedonic samples

Rats were trained in a symbolic delayed matching-to-sample task to discriminate hedonic sample stimuli that consisted of food or no food. Retention functions decreased more rapidly on trials initiated by a food sample than on trials initiated by a no-food sample when retention intervals were manipulated within session. The asymmetrical functions could not be explained in terms of mediation of choice responding by magazine head-entry behavior during the retention interval. Unlike within-session changes in retention interval, between-session changes did not result in steeper forgetting functions for food samples. These results in rats are consistent with previous findings reported for the presence and absence of visual samples in pigeons (Wixted, 1993).     

Influence of feeding rhythm on blood insulin in growing rats]

Plasma insulin in ad libitum fed growing rats increases during dark hours and decreases during light hours. In contrast, meal fed growing rats [6 equal meals at regular interval during the day] exhibit a constant plasma insulin level. It may be inferred that improvement of nitrogen retention in meal fed rats is not related to an increase in insulin secretion.     

Temporal generalization and diffusion in forgetting

Two processes may contribute to the decrement in discriminability with increasing temporal distance between the occasioning event and later choice. One is the length of the interval and the other is generalization decrement. In the model described by White and Wixted [J. Exp. Anal. Behav. 71 (1999) 91-113], choice was predicted by the relative payoff for correct delayed matching responses, conditional on the current value of the stimulus sampled from Thurstone-like probability distributions of the effect of the sample stimuli. In the model, discriminability decreased with increasing temporal distance because the variance of the distributions increased with time. However, White and Wixted did not specify the function relating variance to temporal distance. If a diffusion process is assumed, and if diffusion increases exponentially with time, the resulting forgetting function is a negative exponential. An additional process involves exponential generalization of remembering from one time to other times. Alternative diffusion functions result in hyperbolic or power forgetting functions. The combination of two exponential processes yields forgetting functions that are double exponential in form and which appear consistent with a wide range of data.     

Effects of acute carbon tetrachloride poisoning on vitamin D3 metabolism in the rat

To achieve biologic potency, vitamin D must undergo two successive hydroxylations, first, in the liver and then, in the kidney. Carbon tetrachloride is known to cause extensive damage to the liver, but its effect on vitamin D metabolism has not been studied thoroughly. The effect of carbon tetrachloride on renal hydroxylation of 25-hydroxyvitamin D3 has not been studied. To evaluate the acute effect of carbon tetrachloride on vitamin D metabolism in the liver, vitamin D depleted rats received a single intraperitoneal injection of carbon tetrachloride (2.0 mL/kg body weight). After 24 h, they were given 55, 550, or 5050 pmol [3H]vitamin D3 intravenously. Twenty-four hours after injection of [3H]vitamin D3, aliquots of serum and liver were analyzed for [3H]vitamin D3 and its metabolites by high performance liquid chromatography. Sera of carbon tetrachloride treated rats had higher [3H]vitamin D3 and [3H]25-hydroxyvitamin D and lower [3H]1,25-dihydroxyvitamin D3 concentrations than did control sera. Livers of carbon tetrachloride treated rats contained more [3H]vitamin D3, [3H]25-hydroxyvitamin D3, and more fat. Liver histology showed massive centrilobular necrosis in the treated rats. Thus, our experiment in rats given an acute dose of carbon tetrachloride provided no evidence of impairment of vitamin D metabolism by the liver, but offered a suggestion that 25-hydroxyvitamin D3 metabolism by the kidney might be impaired. To determine the acute effect of carbon tetrachloride on metabolism of vitamin D3 by the kidney, we studied hydroxylation of [3H]25-hydroxyvitamin D3 in isolated perfused kidney. Kidneys from the treated rats showed a 66% reduction in [3H]1,25-dihydroxyvitamin D3 production.