Bilateral cortical circuits are not necessarily symmetrical. Asymmetry, or cerebral lateralization, allows functional specialization of bilateral brain regions and has been described in humans for such diverse functions as perception, memory and emotion. There is also evidence for asymmetry in the human olfactory system, although evidence in non-human animal models is lacking. In the present study, we took advantage of the known changes in olfactory cortical local field potentials that occur over the course of odour discrimination training to test for functional asymmetry in piriform cortical activity during learning. Both right and left piriform cortex local field potential activities were recorded. The results obtained demonstrate a robust interhemispheric asymmetry in anterior piriform cortex activity that emerges during specific stages of odour discrimination learning, with a transient bias toward the left hemisphere. This asymmetry is not apparent during error trials. Furthermore, functional connectivity (coherence) between the bilateral anterior piriform cortices is learning- and context-dependent. Steady-state interhemispheric anterior piriform cortex coherence is reduced during the initial stages of learning and then recovers as animals acquire competent performance. The decrease in coherence is seen relative to bilateral coherence expressed in the home cage, which remains stable across conditioning days. Similarly, transient, trial-related interhemispheric coherence increases with task competence. Taken together, the results demonstrate transient asymmetry in piriform cortical function during odour discrimination learning until mastery, suggesting that each piriform cortex may contribute something unique to odour memory.

Generalized fear is one purported mechanism of anxiety that is a target of clinical and basic research. Impaired fear discrimination has been primarily examined from the perspective of increased fear learning, rather than how learning about non-threatening stimuli affects fear discrimination. To address this question, we tested how three Safety Conditioning protocols with varied levels of salience allocated to the safety cue compared to classic Fear Conditioning in their impact on subsequent innate anxiety, and differential fear learning of new aversive and neutral cues. Using a high anxiety strain of mice (129SvEv, Taconic), we show that Fear Conditioned animals show little exploration of the anxiogenic center of an open field 24 h later, and poor discrimination during new differential conditioning 7 days later. Three groups of mice underwent Safety Conditioning, (i) the safety tone was unpaired with a shock, (ii) the safety tone was unpaired with the shock and co-terminated with a house light signaling the end of the safety period, and (iii) the safety tone was unpaired with the shock and its beginning co-occurred with a house light, signaling the start of a safety period. Mice from all Safety Conditioning groups showed higher levels of open field exploration than the Fear Conditioned mice 24 h after training. Furthermore, Safety Conditioned animals showed improved discrimination learning of a novel non-threat, with the Salient Beginning safety conditioned group performing best. These findings indicate that high anxiety animals benefit from salient safety training to improve exploration and discrimination of new non-threating stimuli.

In current models, learning the relationship between environmental stimuli and the outcomes of actions involves both stimulus-driven and goal-directed systems, mediated in part by the DLS and DMS, respectively. However, though these models emphasize the importance of the DLS in governing actions after extensive experience has accumulated, there is growing evidence of DLS engagement from the onset of training. Here, we used in vivo photosilencing to reveal that DLS recruitment interferes with early touchscreen discrimination learning. We also show that the direct output pathway of the DLS is preferentially recruited and causally involved in early learning and find that silencing the normal contribution of the DLS produces plasticity-related alterations in a PL-DMS circuit. These data provide further evidence suggesting that the DLS is recruited in the construction of stimulus-elicited actions that ultimately automate behavior and liberate cognitive resources for other demands, but with a cost to performance at the outset of learning.

Learning and long-term memory are thought to involve temporally defined changes in gene expression that lead to the strengthening of synaptic connections in selected brain regions. We used cDNA microarrays to study hippocampal gene expression in animals trained in a spatial discrimination-learning paradigm. Our analysis identified 19 genes that showed statistically significant changes in expression when comparing Nai;ve versus Trained animals. We confirmed the changes in expression for the genes encoding the nuclear protein prothymosin(alpha) and the delta-1 opioid receptor (DOR1) by Northern blotting or in situ hybridization. In additional studies, laser-capture microdissection (LCM) allowed us to obtain enriched neuronal populations from the dentate gyrus, CA1, and CA3 subregions of the hippocampus from Nai;ve, Pseudotrained, and spatially Trained animals. Real-time PCR examined the spatial learning specificity of hippocampal modulation of the genes encoding protein kinase B (PKB, also known as Akt), protein kinase C(delta) (PKC(delta)), cell adhesion kinase(beta) (CAK(beta), also known as Pyk2), and receptor protein tyrosine phosphatase(zeta/beta) (RPTP(zeta/beta)). These studies showed subregion specificity of spatial learning-induced changes in gene expression within the hippocampus, a feature that was particular to each gene studied. We suggest that statistically valid gene expression profiles generated with cDNA microarrays may provide important insights as to the cellular and molecular events subserving learning and memory processes in the brain.

Operant discrimination learning was analyzed in pigeons after massive telencephalic lesions. Twenty-one pigeons were divided into three groups: non-lesioned (N = 6), sham-lesioned (N = 5) and telencephalon lesioned (N = 10). Lesion surgeries were carried out before any experimental training. Learning procedures were run in the same sequence for all groups and under a food deprivation of 80% of the ad libitum weight. Successive discrimination was programmed by the alteration of red and yellow lights in the right key of a standard operant chamber: the red key was correlated with variable-ratio reinforcement; the yellow key was correlated with extinction. Session were run until steady-state key peck rates were obtained. The following results demonstrate discrimination learning by detelencephalated birds. Response shaping and steady-state rates required a larger number of sessions for lesioned pigeons (P < 0.05). They showed increased response rates in red (26.43 +/- 2.59) and yellow (11.17 +/- 2.86) components as compared to the non-lesioned (red: 16.51 +/- 2.0; yellow: 2.02 +/- 0.64) and sham-lesioned (red: 22.84 +/- 1.77; yellow: 4.72 +/- 1.99) groups (P < 0.05). These data show that telencephalic systems are not essential for operant discrimination learning but play a role in the modulation of discriminative behavior. Subtelencephalic systems appear to be functionally important for the organization and storage of learning.

Congenital amusia is currently thought to be a life-long neurogenetic disorder in music perception, impervious to training in pitch or melody discrimination. This study provides an explicit test of whether amusic deficits can be reduced with training. Twenty amusics and 20 matched controls participated in four sessions of psychophysical training involving either pure-tone (500 Hz) pitch discrimination or a control task of lateralization (interaural level differences for bandpass white noise). Pure-tone pitch discrimination at low, medium, and high frequencies (500, 2000, and 8000 Hz) was measured before and after training (pretest and posttest) to determine the specificity of learning. Melody discrimination was also assessed before and after training using the full Montreal Battery of Evaluation of Amusia, the most widely used standardized test to diagnose amusia. Amusics performed more poorly than controls in pitch but not localization discrimination, but both groups improved with practice on the trained stimuli. Learning was broad, occurring across all three frequencies and melody discrimination for all groups, including those who trained on the non-pitch control task. Following training, 11 of 20 amusics no longer met the global diagnostic criteria for amusia. A separate group of untrained controls (n = 20), who also completed melody discrimination and pretest, improved by an equal amount as trained controls on all measures, suggesting that the bulk of learning for the control group occurred very rapidly from the pretest. Thirty-one trained participants (13 amusics) returned one year later to assess long-term maintenance of pitch and melody discrimination. On average, there was no change in performance between posttest and one-year follow-up, demonstrating that improvements on pitch- and melody-related tasks in amusics and controls can be maintained. The findings indicate that amusia is not always a life-long deficit when using the current standard diagnostic criteria.

A growing body of evidence implicates the ventral striatum in using information acquired through associative learning. The present study examined the activity of ventral striatal neurons in awake, behaving rats during go/no-go odor discrimination learning and reversal. Many neurons fired selectively to odor cues predictive of either appetitive (sucrose) or aversive (quinine) outcomes. Few neurons were selective when first exposed to the odors, but many acquired this differential activity as rats learned the significance of the cues. A substantial proportion of these neurons encoded the cues' learned motivational significance, and these neurons tended to reverse their firing selectivity after reversal of odor-outcome contingencies. Other neurons that became selectively activated during learning did not reverse, but instead appeared to encode specific combinations of cues and associated motor responses. The results support a role for ventral striatum in using the learned significance, both appetitive and aversive, of predictive cues to guide behavior.

Discriminating membrane proteins based on their functions is an important task in genome annotation. In this work, we have analyzed the characteristic features of amino acid residues in membrane proteins that perform major functions, such as channels/pores, electrochemical potential-driven transporters and primary active transporters.

Sleep supports the consolidation of memory, and it has been proposed that this enhancing effect of sleep pertains in particular to memories which are encoded under control of prefrontal-hippocampal circuitry into an episodic memory system. Furthermore, repeated reactivation and transformation of such memories during sleep are thought to promote the de-contextualization of these memories. Here, we aimed to establish a behavioral model for the study of such sleep-dependent system consolidation in rats, using a go/nogo conditional discrimination learning task known to essentially depend on prefrontal-hippocampal function. Different groups of rats were trained to criterion on this task and, then, subjected to 80-min retention intervals filled with spontaneous morning sleep, sleep deprivation, or spontaneous evening wakefulness. In a subsequent test phase, the speed of relearning of the discrimination task was examined as indicator of memory, whereby rats were either tested in the same context as during training or in a different context. Sleep promoted relearning of the conditional discrimination task, and this effect was similar for testing memory in the same or different context (p < 0.001). Independent of sleep and wakefulness during the retention interval, animals showed faster relearning when tested in the same context as during learning, compared with testing in a different context (p < 0.001). The benefitting effect of sleep on discrimination learning was primarily due to an enhancing effect on response suppression during the nogo stimulus. We infer from these results that sleep enhances memory for inhibitory behavioral control in a generalized context-independent manner and thereby might eventually also contribute to the abstraction of schema-like representations.

A brief image presentation is sufficient to discriminate and individuate objects of expertise. Although perceptual expertise is acquired through extensive practice that increases the resolution of representations and reduces the latency of image decoding and coarse and fine information extraction, it is not known how the stages of visual processing impact object discrimination learning (ODL). Here, we compared object discrimination with brief (100 ms) and long (1,000 ms) perceptual encoding times to test if the early and late visual processes are required for ODL. Moreover, we evaluated whether encoding time and discrimination practice shape perception and recognition memory processes during ODL. During practice of a sequential matching task with initially unfamiliar complex stimuli, we find greater discrimination with greater encoding times regardless of the extent of practice, suggesting that the fine information extraction during late visual processing is necessary for discrimination. Interestingly, the overall discrimination learning was similar for brief and long stimuli, suggesting that early stages of visual processing are sufficient for ODL. In addition, discrimination practice enhances perceive and know for brief and long stimuli and both processes are associated with performance, suggesting that early stage information extraction is sufficient for modulating the perceptual processes, likely reflecting an increase in the resolution of the representations and an early availability of information. Conversely, practice elicited an increase of familiarity which was not associated with discrimination sensitivity, revealing the acquisition of a general recognition memory. Finally, the recall is likely enhanced by practice and is associated with discrimination sensitivity for long encoding times, suggesting the engagement of recognition memory in a practice independent manner. These findings contribute to unveiling the function of early stages of visual processing in ODL, and provide evidence on the modulation of the perception and recognition memory processes during discrimination practice and its relationship with ODL and perceptual expertise acquisition.

Visual discrimination tasks have been widely used to evaluate many types of learning and memory processes. However, little is known about the brain regions involved at different stages of visual discrimination learning. We used cytochrome c oxidase histochemistry to evaluate changes in regional brain oxidative metabolism during visual discrimination learning in a water-T maze at different time points during training. As compared with control groups, the results of the present study reveal the gradual activation of cortical (prefrontal and temporal cortices) and subcortical brain regions (including the striatum and the hippocampus) associated to the mastery of a simple visual discrimination task. On the other hand, the brain regions involved and their functional interactions changed progressively over days of training. Regions associated with novelty, emotion, visuo-spatial orientation and motor aspects of the behavioral task seem to be relevant during the earlier phase of training, whereas a brain network comprising the prefrontal cortex was found along the whole learning process. This study highlights the relevance of functional interactions among brain regions to investigate learning and memory processes.

Previous research suggests an inverse relationship between human orientation discrimination sensitivity and tilt illusion magnitude. To test whether these perceptual functions are inherently linked, we measured both orientation discrimination sensitivity and the magnitude of the tilt illusion before and after participants had been trained for three days on an orientation discrimination task. Discrimination sensitivity improved with training and this improvement remained one month after the initial learning. However, tilt illusion magnitude remained unchanged before and after orientation training, at either trained or untrained orientations. Our results suggest that orientation discrimination sensitivity and illusion magnitude are not inherently linked. They also provide further evidence that, at least for the training periods we employed, perceptual learning of orientation discrimination may involve high-level processes.

Low birth weight (LBW) is a risk factor for cognitive and emotional impairments in humans. In pigs, LBW is a common occurrence, but its effects on cognition and emotion have received only limited scientific attention. To assess whether LBW pigs suffer from impaired cognitive and emotional development, we trained and tested 21 LBW and 21 normal birth weight (NBW) pigs in a judgment bias task. Judgment bias is a measure of emotional state which reflects the influence of emotion on an animal's interpretation of ambiguous stimuli. Pigs were trained to perform a specific behavioral response to two auditory stimuli, predicting either a positive or negative outcome. Once pigs successfully discriminated between these stimuli, they were presented with intermediate, ambiguous stimuli. The pigs' responses to ambiguous stimuli were scored as optimistic (performance of 'positive' response) or pessimistic (performance of 'negative' response). Optimistic or pessimistic interpretation of an ambiguous stimulus is indicative of a positive or negative emotional state, respectively. We found LBW pigs to require more discrimination training sessions than NBW pigs to reach criterion performance, suggesting that LBW causes a mild cognitive impairment in pigs. No effects of LBW on judgment bias were found, suggesting a similar emotional state for LBW and NBW pigs. This was supported by comparable salivary and hair cortisol concentrations for both groups. It is possible the enriched housing conditions and social grouping applied during our study influenced these results.

Several lines of evidence implicate the prefrontal cortex in learning but there is little evidence from studies of human lesion patients to demonstrate the critical role of this structure. To this end, we tested patients with lesions of the frontal lobe (n=36) and healthy controls (n=35) on two learning tasks: the weather prediction task (WPT), and an eight-pair concurrent visual discrimination task ('Choose'). Performance of both tasks was previously shown to be disrupted in patients with Parkinson's disease; the Choose deficit was only present when patients were medicated. Patients with damage to the orbitofrontal cortex (OFC) were significantly impaired on Choose, compared to both healthy controls and non-OFC lesion patients. The OFC lesion patients showed a mild deficit on the first 50 trials of the WPT, compared to the control subjects but not non-OFC lesion patients. The selective deficit in the OFC patients on Choose performance could not be attributed to the larger lesion size in this group, and the deficit was not correlated with the volume of damage to adjacent prefrontal subregions (e.g. anterior cingulate cortex). These data support the notion that the OFC play a role in normal discrimination learning, and suggest qualitative similarities in learning performance of patients with OFC damage and medicated PD patients.

Learning and perception of visual stimuli by free-flying honeybees has been shown to vary dramatically depending on the way insects are trained. Fine color discrimination is achieved when both a target and a distractor are present during training (differential conditioning), whilst if the same target is learnt in isolation (absolute conditioning), discrimination is coarse and limited to perceptually dissimilar alternatives. Another way to potentially enhance discrimination is to increase the penalty associated with the distractor. Here we studied whether coupling the distractor with a highly concentrated quinine solution improves color discrimination of both similar and dissimilar colors by free-flying honeybees. As we assumed that quinine acts as an aversive stimulus, we analyzed whether aversion, if any, is based on an aversive sensory input at the gustatory level or on a post-ingestional malaise following quinine feeding.

Rodent behavioral tasks are crucial to understanding the nature and underlying biology of cognition and cognitive deficits observed in psychiatric and neurological pathologies. Olfaction, as the primary sensory modality in rodents, is widely used to investigate cognition in rodents. In recent years, automation of olfactory tasks has made it possible to conduct olfactory experiments in a time- and labor-efficient manner while also minimizing experimenter-induced variability. In this study, we bring automation to the next level in two ways: First, by incorporating a radio frequency identification-based sorter that automatically isolates individuals for the experimental session. Thus, we can not only test animals during defined experimental sessions throughout the day but also prevent cagemate interference during task performance. Second, by implementing software that advances individuals to the next test stage as soon as performance criteria are reached. Thus, we can prevent overtraining, a known confounder especially in cognitive flexibility tasks. With this system in hand, we trained mice on a series of four odor pair discrimination tasks as well as their respective reversals. Due to performance-based advancement, mice normally advanced to the next stage in less than a day. Over the series of subsequent odor pair discriminations, the number of errors to criterion decreased significantly, thus indicating the formation of a learning set. As expected, errors to criterion were higher during reversals. Our results confirm that the system allows investigating higher-order cognitive functions such as learning set formation (which is understudied in mice) and reversal learning (which is a measure of cognitive flexibility and impaired in many clinical populations). Therefore, our system will facilitate investigations into the nature of cognition and cognitive deficits in pathological conditions by providing a high-throughput and labor-efficient experimental approach without the risks of overtraining or cagemate interference.

Discrimination learning deficits in Parkinson's disease (PD) have been well-established. Using both behavioral patient studies and computational approaches, these deficits have typically been attributed to dopamine imbalance across the basal ganglia. However, this explanation of impaired learning in PD does not account for the possible contribution of other pathological changes that occur in the disease process, importantly including gray matter loss. To address this gap in the literature, the current study explored the relationship between fronto-striatal gray matter atrophy and learning in PD. We employed a discrimination learning task and computational modeling in order to assess learning rates in non-demented PD patients. Behaviorally, we confirmed that learning rates were reduced in patients relative to controls. Furthermore, voxel-based morphometry imaging analysis demonstrated that this learning impairment was directly related to gray matter loss in discrete fronto-striatal regions (specifically, the ventromedial prefrontal cortex, inferior frontal gyrus and nucleus accumbens). These findings suggest that dopaminergic imbalance may not be the sole determinant of discrimination learning deficits in PD, and highlight the importance of factoring in the broader pathological changes when constructing models of learning in PD.

Detection and discrimination of bacteria are crucial in a wide range of industries, including clinical testing, and food and beverage production. Staphylococcus species cause various diseases, and are frequently detected in clinical specimens and food products. In particular, S. aureus is well known to be the most pathogenic species. Conventional phenotypic and genotypic methods for discrimination of Staphylococcus spp. are time-consuming and labor-intensive. To address this issue, in the present study, we applied a novel discrimination methodology called colony fingerprinting. Colony fingerprinting discriminates bacterial species based on the multivariate analysis of the images of microcolonies (referred to as colony fingerprints) with a size of up to 250 μm in diameter. The colony fingerprints were obtained via a lens-less imaging system. Profiling of the colony fingerprints of five Staphylococcus spp. (S. aureus, S. epidermidis, S. haemolyticus, S. saprophyticus, and S. simulans) revealed that the central regions of the colony fingerprints showed species-specific patterns. We developed 14 discriminative parameters, some of which highlight the features of the central regions, and analyzed them by several machine learning approaches. As a result, artificial neural network (ANN), support vector machine (SVM), and random forest (RF) showed high performance for discrimination of theses bacteria. Bacterial discrimination by colony fingerprinting can be performed within 11 h, on average, and therefore can cut discrimination time in half compared to conventional methods. Moreover, we also successfully demonstrated discrimination of S. aureus in a mixed culture with Pseudomonas aeruginosa. These results suggest that colony fingerprinting is useful for discrimination of Staphylococcus spp.

Neuronal pattern separation is thought to enable the brain to disambiguate sensory stimuli with overlapping features, thereby extracting valuable information. In the olfactory system, it remains unknown whether pattern separation acts as a driving force for sensory discrimination and the learning thereof. We found that overlapping odor-evoked input patterns to the mouse olfactory bulb (OB) were dynamically reformatted in the network on the timescale of a single breath, giving rise to separated patterns of activity in an ensemble of output neurons, mitral/tufted (M/T) cells. Notably, the extent of pattern separation in M/T assemblies predicted behavioral discrimination performance during the learning phase. Furthermore, exciting or inhibiting GABAergic OB interneurons, using optogenetics or pharmacogenetics, altered pattern separation and thereby odor discrimination learning in a bidirectional way. In conclusion, we propose that the OB network can act as a pattern separator facilitating olfactory stimulus distinction, a process that is sculpted by synaptic inhibition.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy and the most common neuromuscular disorder. In addition to neuromuscular consequences, some individuals with DMD experience global intellectual dysfunction and executive dysfunction of unknown mechanistic origin. The cognitive profile of the mdx mouse, the most commonly used mouse model of DMD, has been incompletely characterized and has never been assessed using the touchscreen operant conditioning paradigm. The touchscreen paradigm allows the use of protocols that are virtually identical to those used in human cognitive testing and may, therefore, provide the most translational paradigm for quantifying mouse cognitive function. In the present study, we used the touchscreen paradigm to assess the effects of the mdx mutation on visual discrimination learning, serial reversal learning, and extinction learning. To enable measuring task-dependent learning and memory processes while holding demands on sensory-driven information processing constant, we developed equally salient visual stimuli and used them on all experimental stages. Acquisition of the initial pairwise visual discrimination was facilitated in mdx mice relative to wildtype littermates; this effect was not explained by genotypic differences in impulsivity, motivation, or motor deficits. The mdx mutation had no effect on serial reversal or extinction learning. Together, findings from this study and previous studies suggest that mdx effects on cognitive function are task-specific and may be influenced by discrimination type (spatial, visual), reward type (food, escape from a non-preferred environment), sex, and genetic background.