Differential effect of thalamic and cortical lesions on memory systems in the rat.

The behavioral effects of lesions of anterior thalamic and medio-dorsal thalamic nuclei, posterior cingulate (retrosplenial) and posterior parietal associative cortex were studied in rats performing a eight-arm radial maze, in which three/eight arms were baited. Lesions were made after rats reached a training criterion. Rats were tested 2 weeks later, in the same experimental apparatus. In the first experiment, performance was assessed by number of errors and time per trial, retention by comparing performance during training with retraining sessions (using specific scores for reference and working memory) and by an evaluation of the 'reminiscence' defined as daily improvement in performance. After the reacquisition of the task, the rats were tested in experiment II, in modified situations for an evaluation of flexible aspects of memory processing in this spatial task. Results showed dissociation between the effects of the different lesions, according to the specific demands of the different tasks. Posterior parietal lesions produced significant, but relatively mild deficits, in all situations, in accordance with the well-established function of this cortical region in spatial tasks. In contrast, after cortical lesion in the retrosplenial region, performance deficit was only observed on priming and attention to contextual change. Lesions of the thalamic associative nuclei also induced task-specific deficits. Medio-dorsal lesions induced mild and reversible deficits in complex tasks only, with preservation of working memory, of priming effect, and of a novel acquisition. Rats with anterior thalamic lesions had massive deficits across tasks, probably due to basic difficulties with reference and working memory, demonstrated no benefit from a priming session but considerable interference from the previous training to a new one. These results are discussed within framework of the specificity of different cerebral regions for behavioural adaptation and plasticity.

Antibody to day-old chick brain glycoprotein produces amnesia in adult rats.

Polyclonal antibody R-1, raised against a chick synaptic membrane glycoprotein fraction whose synthesis is enhanced following training on a passive avoidance task, produces amnesia when injected into chick forebrain 5.5 h posttraining. The amnestic IgG fraction specifically recognizes a low sialylated isoform of NCAM (Mileusnic Rose, Lancashire, & Bullock, 1995). We have now investigated the effects of this antibody on memory formation in adult rats. R-1, preimmune serum, or saline was injected intracerebroventricularly 5.5 h posttraining through bilaterally implanted cannulae. Rats injected with R-1 and tested 48 h later showed a significant amnesia for avoidance compared with the controls. Amnesia was not apparent at 24 h posttraining. R-1 injections were without effect on spontaneous locomotor or exploratory activity in a holeboard test. The results contribute to the argument that the role of cell adhesion molecules in neuronal plasticity is not limited to the developing nervous system, but they play a more general role in the experience-dependent synaptic remodeling underlying long-term memory.

Locus coeruleus neurons in monkey are selectively activated by attended cues in a vigilance task.

Impulse activity was recorded extracellularly from noradrenergic neurons in the nucleus locus coeruleus (LC; 47 single-cell and 126 multicell recordings) of four cynomolgus monkeys performing an oddball visual discrimination task. For juice reward, the subjects were required to release a lever rapidly in response to an infrequent (10-20% of trials) target cue (CS+) that was randomly intermixed with nontarget (CS-) stimuli presented on a video display. All LC neurons examined were phasically and selectively activated by target cues in this task. Other task events elicited no consistent response from these neurons (juice reward, lever release, fix-spot stimuli, nontarget stimuli). In one animal, nontarget cues phasically inhibited LC neurons. Phasic LC excitatory responses to target cues in this task occurred at a relatively short latency (mean = 90.7 msec), approximately 200 msec prior to the behavioral response (lever release). In addition, LC response magnitudes varied with behavioral performance, being substantially attenuated during epochs of poor performance (high false alarm rate). There was a positive correlation (r = 0.30, p < 0.0001) between the latency of LC responses and the latency of behavioral responses to same target cues, consistent with the possibility that LC responses may have a role in selective attention by facilitating responses to the CS+ stimulus. Analyses of behavioral response latencies to pairs of stimuli indicated that LC responses may facilitate behavioral responses to subsequent sensory cues, consistent with a role of this system in sustained attention/vigilance. Moreover, responses became reduced in magnitude over time during prolonged task performance (> 90 min), in parallel with a behavioral performance decrement. These results show that LC neurons are activated selectively by attended stimuli that demand a rapid response in this task, and that such LC responses may contribute to conditioned behavioral responses.

Food-restriction interacts with vasopressin modulation of activity.

The effects of peripheral injection of various doses of lysine-vasopressin (LVP), administered 30 min before a 5-min session in a hole-board apparatus, were compared as a function of food restriction. Comparison of performance for various indices of general activity clearly showed that the food-restricted rats were more active and exhibited less photophobia than normally fed ones. The differences between the two groups were maintained in a second session 24 hours later. There was no sign of behavioral habituation to the apparatus among restricted animals. Different doses (0.2, 1, 2 micrograms of LVP) affected food-restricted animals differently from the rats fed ad lib. Only the highest dose reduced activity in both groups. A posttest injection of the smallest dose (0.2 micrograms) had an opposite effect on the activity in the hole-board, measured 24 hours after the injection. A second experiment showed that plasma and adrenal corticosterone were higher in deprived rats. The administration of 0.2 micrograms of LVP was followed by an increase in corticosterone. In food-restricted rats this increase was bigger and was still observed 24 hours after the injection. There is an interaction between feeding conditions and LVP injections which affects both the internal hormonal state and spontaneous reactivity to environment. These findings are of relevance to the effect of vasopressin on behavior.

Discharge of noradrenergic locus coeruleus neurons in behaving rats and monkeys suggests a role in vigilance.

Recordings from noradrenergic locus coeruleus (LC) neurons in behaving rats and monkeys revealed that these cells decrease tonic discharge during sleep and also during certain high arousal behaviors (grooming and consumption) when attention (vigilance) was low. Sensory stimuli of many modalities phasically activated LC neurons. Response magnitudes varied with vigilance, similar to results for tonic activity. The most effective and reliable stimuli for eliciting LC responses were those that disrupted behavior and evoked orienting responses. Similar results were observed in behaving monkeys except that more intense stimuli were required for LC responses. Our more recent studies have examined LC activity in monkeys performing an "oddball" visual discrimination task. Monkeys were trained to release a lever after a target cue light that occurred randomly on 10% of trials; animals had to withhold responding during non-target cues. LC neurons selectively responded to the target cues during this task. During reversal training, LC neurons lost their response to the previous target cue and began responding to the new target light in parallel with behavioral reversal. Cortical event-related potentials were elicited in this task selectively by the same stimuli that evoked LC responses. Injections of lidocaine, GABA, or a synaptic decoupling solution into the nucleus paragigantocellularis in the rostral ventrolateral medulla, the major afferent to LC, eliminated responses of LC neurons to sciatic nerve stimulation or foot- or tail-pinch. This indicates that certain sensory information is relayed to LC through the excitatory amino acid (EAA) input from the ventrolateral medulla. The effect of prefrontal cortex (PFC) activation on LC neurons was examined in anesthetized rats. Single pulse PFC stimulation had no pronounced effect on LC neurons, consistent with our findings that this area does not innervate the LC nucleus. However, trains of PFC stimulation substantially activated most LC neurons. Thus, projections from the PFC may activate LC indirectly or through distal dendrites, suggesting a circuit whereby complex stimuli may influence LC neurons. The above results, in view of previous findings for postsynaptic effects of norepinephrine, are interpreted to reveal a role for the LC system in regulating attentional state or vigilance. The roles of major inputs to LC from the ventrolateral and dorsomedial medulla in sympathetic control and behavioral orienting responses, respectively, are integrated into this view of the LC system. It is proposed that the LC provides the cognitive complement to sympathetic function.

Long-term spontaneous improvement of performance is related to the strength of the initial training: theoretical implications.

In a recent study we established that following a partial acquisition of a brightness discrimination escape task (15 trials), Sprague-Dawley albino rats exhibited a long-term spontaneous improvement of performance (LTSI) after 7 to 14 days. Some evidence suggests a relation between the strength of the initial training and the delay of the optimal retention performance. This study investigates such a possibility in studying performance of rats (number of trials needed to reach a criterion of 10 errorless trials) following nine different retention intervals: 10 min, and 1, 3, 5, 7, 10, 14, 21, and 28 days, after a strengthened initial training (25 trials). Under those conditions, LTSI occurred after a delay of 5 to 7 days. Theoretical implications for an inverse relationship between the strength of initial training and the length of delay leading to LTSI are discussed.

Vasopressin injections impair working memory in a delayed matching to sample task in rats.

Effects of vasopressin were measured in a nonspatial working memory task: food-reinforced, delayed matching to sample. Subcutaneous injections of 0.2 microgram of lysine vasopressin (LVP) or saline were alternately administered to Sprague-Dawley rats after the presentation of the sample and compared to the effect of the same treatments given to a yoked control group of rats. Different durations of sample presentation (5 and 30 min) and various retention intervals (10 min, 3 h, 24 h) were selected. The results showed that LVP never facilitated retention performance: there was no improvement under conditions of weak memory (short presentation of the sample and long retention interval); moreover LVP abolished the facilitation normally obtained when either the length of the sample presentation was longer or the duration of the retention interval was shorter. The performance after the injection of the peptide was differentially impaired, according to brightness of the sample which had been presented: after the presentation of the white box, LVP injections lead to more errors and after that of the black one the treatment induced an increase in latencies of response. All these data may suggest that the physiological consequences of hormonal modifications triggered by the LVP injection are processed along with the stimuli of the learning episode and interfere with the learned positive value of the sample.

Repeated post trial administration of vasopressin impairs subsequent Differential Reinforcement of Low rates (DRL) performance.

Twenty-six male rats, maintained on a 23-h food deprivation regime, were trained on a DRL learning schedule. During pretraining (CRF) rats were placed in two groups according to speed in obtaining the criterion (good and poor learners). The performance of good and poor learners, injected with lysine vasopressin (LVP) immediately after each training session, was compared with that of control good and poor learners injected with saline. During the first DRL 20 stage, injected rats had fewer reinforcements than control rats. Fifty-five days later, during reacquisition of DRL 20, LVP rats again had fewer reinforcements, especially those which were formerly good learners in the CRF stage. Nonetheless, treated rats were able to shift their rate of responding from high to low frequency. A reduction of the minimal interresponse time to 16 s showed that LVP rats were able to adapt to this condition and that, in a further DRL 20 stage, the difference between the two groups was no longer significant. The results are discussed in terms of a modification of the behavioral expression of a learned response, without a specific action on memory processes.

Effects of posttrial vasopressin injections on appetitively motivated learning in rats.

Sixty male rats, maintained on 23-hr food deprivation were trained on two types of appetitive tasks: bar pressure responding under a CRF schedule, and under a differentially reinforced (light+, dark-) schedule. Performance of rats treated with lysing vasopressin, injected immediately after each training session, was compared to that of control animals injected with saline. In the CRF stage, treated animals reached learning criterion significantly later than did control rats, and made significantly fewer bar presses. During acquisition and extinction of a light-dark discrimination, learning and retention were not altered by vasopressin, though the number of bar presses was significantly decreased, and a differential effect was found according to previous CRF performance. The results are discussed considering the hypothesis of a facilitatory effect of vasopressin on memory processes.

[Aversive effects of halothane anesthesia in the rat, using extinction of tasks by positive reinforcement]. / Mise en évidence d'effets aversifs d'une narcose au fluothane par l'utilisation de la phase d'extinction d'apprentissages à renforcement postif chez le rat.

Immediate posttrial halothane anaesthesia accelerates the extinction of two previously acquired operant tasks--barpress learning or modified K-maze learning. This acceleration is not due to any motor impairment. These results are not consistent with the hypothesis of amnestic effects of halothane anaesthesia; they are interpreted in terms of aversive effects.