Perirhinal cortex lesions impair simultaneous but not serial feature-positive discrimination learning

The role of the perirhinal cortex in discriminative eyeblink conditioning was examined by means of feature-positive discrimination procedures with simultaneous (A-/XA+) and serial (A-/X-->A+) stimulus compounds. Lesions of the perirhinal cortex severely impaired acquisition of simultaneous feature-positive discrimination but produced no impairment in serial feature-positive discrimination. The results suggest that the perirhinal cortex plays a role in discriminative eyeblink conditioning by resolving ambiguity in discriminations with overlapping stimulus elements.     

Perirhinal cortex and anterior thalamic lesions: comparative effects on learning and memory

Three learning and memory tasks were used to compare the effects of neurotoxic anterior thalamic nuclei (ATN) and perirhinal cortex (PRC) lesions in rats. Rats with ATN lesions showed impaired spatial memory in a 12-arm radial maze, whereas rats with PRC lesions showed intact spatial memory, despite the use of minimal pretraining and extensive within-session delays (to 40 rain). PRC, but not ATN, lesions produced impairments on a configural learning task using complex visual-tactile cues in the radial maze. Neither ATN nor PRC lesions consistently affected spontaneous object recognition across extended sample-test delays (to 40 min). These findings confirm the differential involvement of the ATN and PRC in learning and memory.     

Interaction of ventral and orbital prefrontal cortex with inferotemporal cortex in conditional visuomotor learning

Five rhesus monkeys (Macaca mulatta) were trained to learn novel conditional visuomotor associations, to perform this task with familiar stimuli, and to perform a visual matching-to-sample task with the same familiar stimuli. Removal of the orbital and ventral prefrontal cortex (PFv+o) in 1 hemisphere and inferotemporal cortex (IT) in the other, thus completing a surgical disconnection of these 2 regions, yielded an impairment on all 3 tasks. Addition of a premotor cortex lesion to the hemisphere containing the PFv+o lesion did not worsen the impairments. The results indicate that PFv+o interacts with IT in both the learning and retention of conditional visuomotor associations. In addition to those associations, which might be considered lower order rules for choosing a response, frontotemporal interaction also appears to be important for higher order rules, such as those involved in the matching task.     

Representations of odors in the rat orbitofrontal cortex change during and after learning

Cells in the orbitofrontal cortex (OF) respond to odors and their associated rewards. To determine how these responses are acquired and maintained, the authors recorded single OF units in rats performing an odor discrimination task. Approximately 64% of all cells differentiated between rewarded and nonrewarded odors. These odor valence responses changed during learning in 26% of all cells, and these changes were positively correlated with improving performance, supporting the idea that the information provided by these cells is used in learning the task. However, changes in odor valence responses were also observed after learning, and included not only increases in odor discrimination, but also decreases or mixed increases and decreases. Thus, only some of the changes in firing reflected acquisition of the task. The results suggest that learning triggers a continuing reorganization of OF neural ensembles representing odors and their rewards.     

Effects of early postnatal gonadal steroids on the successive conditional discrimination reversal learning in the rat

In the present study the existence of sex differences in the acquisition, retraining and reversal of a successive conditional discrimination learning (Experiment 1) and the role of the early postnatal gonadal steroids on these discrimination tasks (Experiment 2) were investigated. In Experiment 1 two groups of experimentally naive rats (males and females) were exposed to a black-white successive conditional discrimination task in a T-maze. No sex differences were found in the acquisition or retraining. However, in the reversal phase females made fewer errors and reached the discrimination criterion (90% of correct choices) sooner than males. In Experiment 2, the absence of sex differences in the acquisition or retraining phases and the existence of sexual dimorphism in the reversal period were confirmed. In addition, female androgenization and male orchidectomy, on day one after birth, reversed the direction of the sex differences found in the successive conditional discrimination reversal learning.     

Perirhinal cortex ablation in rats selectively impairs object identification in a simultaneous visual comparison task

In Experiment 1, rats discriminated among computer-generated visual displays (scenes) comprising 3 different shapes (objects). One constant scene (unrewarded) appeared on every trial together with a trial-unique variable scene (rewarded). Four types of variable scene were intermingled: (a) unfamiliar objects in different positions from the constant; (b) unfamiliar objects in same positions as the constant; (c) same objects as the constant in different positions; (d) same objects and positions, recombined. Aspiration lesions of perirhinal cortex impaired performance with type (b) only. Experiment 2 tested spatial delayed nonmatching-to-sample. The perirhinal group were impaired nonsignificantly, and less than fornix-transected rats in an earlier study. Rats' perirhinal cortex, like monkeys', subserves object identification in the absence of memory requirement but does not contribute substantially to hippocampal system spatial memory function.     

Fos expression and task-related neuronal activity in rat cerebral cortex after instrumental learning

Learning has been shown to induce changes in neuronal gene expression and to produce development of task-specific neuronal activity. The connection between these two features of neuronal plasticity remains of a great interest. To address this issue we compared distribution of c-Fos expressing and task-related neurons in the rat cerebral cortex following instrumental learning of appetitive lever-press task. The number of Fos-positive neurons was determined immunohistochemically in the retrosplenial and the motor cortex of naive ("control" group), newly trained ("acquisition" group) and overtrained ("performance" group) animals. A significant activation of c-Fos expression was observed in the neurons of the retrosplenial but not motor cortex in the "acquisition" group rats, as compared with the "control" and "performance" groups. In accordance with this c-Fos expression difference, the retrosplenial cortex of the trained animals contained significantly more neurons with lever-press-related activity than the motor cortex. Therefore, the two examined cortical areas showed a parallel between experience-dependent induction of c-Fos and development of task-related neuronal activity. These data support a notion that learning-induced activation of c-Fos is associated with long-term neurophysiological changes produced by training.     

Spatial conditional discrimination learning in developing rats

The present study established an effective procedure for studying spatial conditional discrimination learning in juvenile rats using a T-maze. Wire mesh located on the floor of the maze as well as a second, identical T-maze apparatus served as conditional cues which signaled whether a left or a right response would be rewarded. In Experiment 1, conditional discrimination was evident on Postnatal Day (PND) 30 when mesh+maze or maze-alone were the conditional cues, but not when mesh-alone was the cue. Experiment 2 confirmed that mesh-alone was sufficiently salient to support learning of a simple (nonconditional) discrimination. Its failure to serve as a conditional cue in Experiment 1 does not reflect its general ineffectiveness as a stimulus. Experiment 3 confirmed that the learning shown in Experiment 1 was indeed conditional in nature by comparing performance on conditional versus nonconditional versions of the task. Experiment 4 showed that PND19 and PND23 pups also were capable of performing the task when maze+mesh was the cue; however, the findings indicate that PND19 subjects do not use a conditional strategy to learn this task. The findings suggest postnatal ontogeny of conditional discrimination learning and underscore the importance of conditional cue salience, and of identifying task strategies, in developmental studies of conditional discrimination learning.     

The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatta)

Four rhesus monkeys (Macaca mulatta) were trained to learn novel sets of visuomotor associations in 50 trials or less, within single test sessions. After bilateral ablation of the orbital and ventral prefrontal cortex, the monkeys lost the ability to learn these associations within a session, although they could learn them when given several daily sessions. Thus, relatively slow, across-session visuomotor learning depends on neither the ventral nor orbital prefrontal cortex, but rapid, within-session learning does. The ablations also eliminated at least 2 response strategies, repeat-stay and lose-shift, which might account, in part, for the deficit in rapid learning. The deficit is unlikely to result from a failure of visual discriminative ability or working memory: The monkeys could discriminate similar stimulus material within a session, and reducing the working memory load did not improve within-session learning.     

Neuronal activity in the monkey striatum during conditional visuomotor learning

The brainstem projection of the saccular nerve was investigated by transganglionic tracing with horseradish peroxidase in the cat. The labeled fibers were located most caudally and laterally (dorsolaterally) in the vestibular nerve root. This was unique when compared with the locations of the fibers from the nerves of the other vestibular-end organs that were studied by the present authors by the same approach previously. In addition, such a comparison revealed a specific location, from lateral to medial, for the fibers from each of the five divisions of the vestibular nerve. In the present study, labeled fibers from the sacculus, of fine caliber, were found close to the restiform body, both medially and laterally, some even penetrating through this structure. Labeled terminals were present in cell group "y". This was unique, compared with the nerves from the other end organs. Such terminals were also found in the four main vestibular nuclei, except for the medial vestibular nucleus, where no labeled terminals could be detected. No labeled terminals were found in the interstitial nucleus of the vestibular nerve. Together with the findings from our previous studies, this suggests that, in contrast to the ampullar nerves, the nerves from the maculae do not project to this structure. This study confirms, but also extends, findings reported from a previous investigation in the cat, using an experimental degeneration technique. This article is based on experimental material that was prepared before the untimely death of Dr. Siegborn in 1997. He took active part in the planning of this study, and he carried out all of the microsurgery     

Involvement of the lateral prefrontal cortex in conditional suppression of gaze shift

Conditional execution and suppression of gaze shift are important in everyday life. To examine the possible involvement of the lateral prefrontal cortex (LPFC) in this process, we induced a local and reversible inactivation by injecting muscimol into 66 sites within the LPFC of monkeys and examined muscimol's effect on their performance in an oculomotor Go/No-Go task. This task required a subject to execute (Go) or suppress (No-Go) its gaze toward a target location in response to an instructional visual cue. Local injection of muscimol into 22 regions of the LPFC resulted in significant increases in the number of error saccades toward a few specific target locations during No-Go trials, whereas there were no error saccades in the Go trials. The onset latency of error saccades in No-Go trials was significantly longer than that of correct saccades in Go trials, but their velocity and amplitude were similar to those of correct saccades in Go trials. Go correct saccades appeared intact after the injections. These findings provide evidence that different regions of the LPFC are involved in the conditional suppression of gaze shift toward a few specific target locations, which may occur through a top-down suppressive mechanism.     

Sound sequence discrimination learning is dependent on cholinergic inputs to the rat auditory cortex

In rat auditory cortex (AC) slices, synaptic potentiation following heterosynaptic stimulation is affected by the stimulus sequence used for induction. It was hypothesized that this sequence-dependent plasticity might be partly involved in the cellular mechanisms underlying sound sequence discrimination. Sequence dependence is abolished by muscarinic receptor antagonists. Therefore, dependence of sound sequence discrimination learning on cholinergic inputs to the rat AC was investigated. Rats were trained to discriminate the sequences of two sound components and a licking behavior in response to one of two possible sequences was rewarded with water. Atropine, a muscarinic receptor antagonist, attenuated sound sequence discrimination learning. The acquired sound sequence discrimination was not affected by atropine. Injections of the cholinergic immunotoxin 192IgG-saporin into the AC suppressed sound sequence discrimination learning, while discrimination between the two sound components was not affected. An inhibitor of M-current, linopirdine, restores the sequence dependence of synaptic potentiation in the AC slices suppressed by atropine. In this study, sound sequence discrimination learning attenuated by 192IgG-saporin was also restored by linopirdine. These similarities between sequence dependent plasticity in the AC slices and sound sequence discrimination learning support the hypothesis that the former is involved in the cellular mechanisms underlying the latter.     

Cortical noradrenaline depletion eliminates sparing of spatial learning after neonatal frontal cortex damage in the rat

The possibility that cortical noradrenaline (NA) is necessary for the sparing of function that occurs after neonatal frontal cortex damage was examined. Spatial localization by rats with frontal cortex damage sustained neonatally was better than by rats with similar damage sustained as adults. The sparing was abolished in rats depleted of cortical noradrenaline by means of neonatal 6-hydroxydopamine (6-OHDA) administration. NA depletion alone did not affect spatial localization. These data are consistent with the motion that NA has some general function in maintaining some forms of plasticity in posterior cortex.     

Impairment of learning and memory after photothrombosis of the prefrontal cortex in rat brain: effects of Noopept

Experiments were performed on rats trained conditioned passive avoidance response. Acquisition and retention of memory traces were impaired after photothrombosis of the prefrontal cortex. The acyl-prolyl-containing dipeptide Noopept facilitated retention and retrieval of a conditioned passive avoidance response, normalized learning capacity in animals with ischemic damage to the cerebral cortex, and promoted finish training in rats with hereditary learning deficit. These results show that Noopept improves all three stages of memory. It should be emphasized that the effect of Noopept was most pronounced in animals with impaired mnesic function.     

Single-unit responses in the auditory cortex of monkeys performing a conditional acousticomotor task

The general goal of the present study was to assess the response properties to tones of single neurons in the auditory cortex (primary auditory area, A1, and middle lateral auditory belt, ML) of two macaque monkeys while performing an acousticomotor discrimination task requiring a controlled level of attention and motivation. For each neuron, an approximation of the frequency receptive field (FRF) was first established. Second, based on the FRF, sets of paired tone frequencies were defined in which two different tone frequencies had to be associated by the monkey, following a trial and error strategy, to a left or a right key-press with the left arm. After acquisition of the association, the two tones of the pair were presented randomly (instruction stimulus) and, if the monkey touched the correct key, the stimulus was repeated (confirmation stimulus) and a reward was delivered. The majority of units (63%) had a FRF formed by multiple peaks, whereas 25% and 12% of units exhibited a simple U-shaped FRF and a mosaic FRF, composed of several separated zones of response, respectively. Five principal response patterns were observed: On, Off, On-Off, Sustained, and Inhibition. In relation to the acousticomotor association task, some auditory cortical neurons (33%) exhibited a different response to the same stimulus when presented, in the same trials, as instruction or as confirmation. It was also observed that the response to the same instruction stimulus could differ when comparing correct trials with erroneous trials (wrong motor response). In conclusion, the response properties of auditory cortical neurons in behaving monkeys are strongly dependent on the physical parameters of sounds (frequency, intensity, etc.) as indicated by FRF characteristics, but a substantial influence of the behavioral context and performance may also play an important role.     

Neuronal encoding of conditional stimulus duration in the cingulate cortex and the limbic thalamus of rabbits

Neuronal activity in cingulate cortex was recorded during discriminative active avoidance conditioning of rabbits. In one subpopulation of neurons, brief (200 and 500 ms) conditional stimuli (CSs) elicited greater average cingulate cortical training-induced neuronal discharges during conditioned response acquisition than did a long (5,000 ms) CS, and the amount of neuronal discrimination between CS+ and CS- was greater in response to the brief CSs than to the long CS. Neurons in a different subpopulation did not encode CS duration per se but were sensitive to the novelty of the CS duration. Medial dorsal and anteroventral thalamic neurons were suppressed by novel CS durations that activated novelty-sensitive neurons in related cingulate cortical areas. These results are discussed in relation to a theoretical model of the neural mediation of avoidance conditioning.     

Contribution of the amygdala to learning and performance of conditional fear.

The amygdaloid complex appears to be an essential component in the neural systems mediating some forms of aversive Pavlovian conditioning. The relative contribution of this structure to acquisition and performance during fear conditioning was assessed by making temporary lesions in the amygdala prior to training or retention testing in a single-trial Pavlovian conditioning preparation. Microinjection of lidocaine HCl (5.0%, 1.0 microliters) into the amygdala prior to the presentation of a CS signalling footshock resulted in a significant attenuation of the performance of conditional fear, as indexed by the amount of time rats spent engaged in defensive freezing behavior during the retention session. However, similar treatment with lidocaine prior to the training session, during which the CS and UCS were paired, resulted in only a weak reduction in subsequent responding. Thus, while both acquisition- and performance-related processes take place within the amygdala, it appears that the latter are more sensitive to disruption using the present procedures. These results are discussed in terms of the general role played by this structure in aversive learning and motivational processes.     

Effects of age and awareness on eyeblink conditional discrimination learning

The present study aimed to assess the effects of aging and awareness on conditional discrimination learning within an eyeblink conditioning procedure by using a consecutive age-groups design (20-35 years, 36-50 years, 51-65 years, 66-80 years). Increasing age was associated with a decline in overall eyeblink conditioned response (CR) frequency and a deficit in conditional discrimination learning in the 2 older groups. Awareness of stimulus contingencies affected discrimination performance but not overall CR rates in younger subjects. Older subjects did not achieve eyeblink conditional discrimination learning, regardless of awareness. Discrimination performance correlated with measures of declarative memory. The pattern of results is discussed with respect to the involvement of hippocampal-cerebellar interactions and awareness in the mediation of age-related conditioning changes.     

大鼠海马和颞叶一氧化氮合酶阳性神经元在学习记忆时的表达

目的　对获得空间辨别性学习记忆大鼠的海马结构和颞叶皮质内一氧化氮合酶 (NOS)免疫阳性神经元系统的观察 ,为一氧化氮 (NO)在学习记忆活动中的作用提供形态学依据。方法　以经水迷宫训练获得空间辨别性学习记忆的大鼠为模型组 ,建立游水对照组和空白对照组。用免疫组化的方法观察 3组大鼠海马和颞叶的NOS阳性神经元的形态学特征及测定免疫反应阳性产物的光密度值 (OD )。结果　 (1)NOS阳性神经元在 3组大鼠海马和颞叶呈散在分布。在海马CA1、CA2、CA3、CA4及龄状回 (DG)都有少量分布 ,颞叶以Ⅱ、Ⅲ、Ⅴ、Ⅵ层分布为主。神经元胞体形态有锥体形 ,圆形或椭圆形 ,梭形3种。 (2 )模型组大鼠海马和颞叶皮质NOS阳性神经元较对照组明显增多。 (3)其免疫反应阳性产物的OD值也较对照组明显增大。结论　NOS阳性神经元形态发生了可塑性变化 ,参与了学习记忆