The negatively accelerated, gradually increasing learning curve is an artifact of group averaging in several commonly used basic learning paradigms (pigeon autoshaping, delay-and trace-eyeblink conditioning in the rabbit and rat, autoshaped hopper entry in the rat, plus maze performance in the rat, and water maze performance in the mouse). The learning curves for individual subjects show an abrupt, often step-like increase from the untrained level of responding to the level seen in the well trained subject. The rise is at least as abrupt as that commonly seen in psychometric functions in stimulus detection experiments. It may indicate that the appearance of conditioned behavior is mediated by an evidence-based decision process, as in stimulus detection experiments. If the appearance of conditioned behavior is taken instead to reflect the increase in an underlying associative strength, then a negligible portion of the function relating associative strength to amount of experience is behaviorally visible. Consequently, rate of learning cannot be estimated from the group-average curve; the best measure is latency to the onset of responding, determined for each subject individually.

SUMMARY Cognitive deficits are central to schizophrenia but the underlying mechanisms still remain unclear. Imaging studies performed in patients point to decreased activity in the medio-dorsal thalamus (MD) and reduced functional connectivity between the MD and prefrontal cortex (PFC) as candidate mechanisms. However, a causal link is still missing. We used a pharmacogenetic approach in mice to diminish MD neuron activity and examined the behavioral and physiological consequences. We found that a subtle decrease in MD activity is sufficient to trigger selective impairments in prefrontal-dependent cognitive tasks. In vivo recordings in behaving animals revealed that MD-PFC beta-range synchrony is enhanced during acquisition and performance of a working memory task. Decreasing MD activity interfered with this task-dependent modulation of MD-PFC synchrony, which correlated with impaired working memory. These findings suggest that altered MD activity is sufficient to disrupt prefrontal-dependent cognitive behaviors, and could contribute to the cognitive symptoms observed in schizophrenia.

Neurobiological research on learning assumes that temporal contiguity is essential for association formation, but what constitutes temporal contiguity has never been specified. We review evidence that learning depends, instead, on learning a temporal map. Temporal relations between events are encoded even from single experiences. The speed with which an anticipatory response emerges is proportional to the informativeness of the encoded relation between a predictive stimulus or event and the event it predicts. This principle yields a quantitative account of the heretofore undefined, but theoretically crucial, concept of temporal pairing, an account in quantitative accord with surprising experimental findings. The same principle explains the basic results in the cue competition literature, which motivated the Rescorla-Wagner model and most other contemporary models of associative learning. The essential feature of a memory mechanism in this account is its ability to encode quantitative information. Associative learningThe associative aspect of learning can be understood in a broad or a narrow sense. When understood in the broad sense, 'associative' implies only that the subject has learned a relation between two things. In this sense, we can say that a subject has associated X and Y when they have learned that event Y follows event X at an interval of ∼10 s. When used in this sense, 'associations' encode information: the brain can recover the exact relation (e.g. temporal) and parameters (duration values) from the structure of the association * .When understood in the narrow sense, 'associative' implies the formation of a signalconducting connection between the internal representations of two events. The activation of one representation excites or inhibits the other by signals transmitted through the connection. The connection does not specify the nature (e.g. spatial, temporal, causal or categorical) or parameters (e.g. 10 s, 5 km, etc) of the relation between what it connects. An experienced temporal relation between events is often assumed to be essential for the formation of an association in this narrow sense. However, the association thus formed does not encode information [2][3][4]. The duration of the interval separating the associated events cannot be recovered by 'reading' or 'transcribing' the association.Association formation in the narrow sense is plausibly thought to be realized by changes in synaptic conductance. When understood in the broad sense, however, the possible dependence © 2008 Elsevier Ltd. All rights reserved.Corresponding author: Balsam, P.D. (balsam@columbia.edu). * We mean Shannon information: a spatio-temporal structure can encode information if it can specify a message from among a set of possible messages [1]. The structure of a codon in an exon (the sequence of 3 nucleotides) specifies which of 4 3 = 64 possible messages was transmitted from a parent (or which of 20 messages if one considers the degeneracy of the genetic code for amino acids). In a computer, the structure ...

The striatum receives prominent dopaminergic innervation that is integral to appetitive learning, performance, and motivation. Signaling through the dopamine D 2 receptor is critical for all of these processes. For instance, drugs with high affinity for the D 2 receptor potently alter timing of operant responses and modulate motivation. Recently, in an attempt to model a genetic abnormality encountered in schizophrenia, mice were generated that reversibly overexpress D 2 receptors specifically in the striatum (Kellendonk et al., 2006). These mice have impairments in working memory and behavioral flexibility, components of the cognitive symptoms of schizophrenia, that are not rescued when D 2 overexpression is reversed in the adult. Here we report that overexpression of striatal D 2 receptors also profoundly affects operant performance, a potential index of negative symptoms. Mice overexpressing D 2 exhibited impairments in the ability to time food rewards in an operant interval timing task and reduced motivation to lever press for food reward in both the operant timing task and a progressive ratio schedule of reinforcement. The motivational deficit, but not the timing deficit, was rescued in adult mice by reversing D 2 overexpression with doxycycline. These results suggest that early D 2 overexpression alters the organization of interval timing circuits and confirms that striatal D 2 signaling in the adult regulates motivational process. Moreover, overexpression of D 2 under pathological conditions such as schizophrenia and Parkinson's disease could give rise to motivational and timing deficits.