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Positive reinforcement helps to control the acquisition of learned behaviours. Here we report a cellular mechanism in the brain that may underlie the behavioural effects of positive reinforcement. We used intracranial self-stimulation (ICSS) as a model of reinforcement learning, in which each rat learns to press a lever that applies reinforcing electrical(More)
There is a large body of data on the firing properties of dopamine cells in anaesthetised rats or rat brain slices. However, the extent to which these data relate to more natural conditions is uncertain, as there is little quantitative information available on the firing properties of these cells in freely moving rats. We examined this by recording from the(More)
Behavioral conditioning of cue-reward pairing results in a shift of midbrain dopamine (DA) cell activity from responding to the reward to responding to the predictive cue. However, the precise time course and mechanism underlying this shift remain unclear. Here, we report a combined single-unit recording and temporal difference (TD) modeling approach to(More)
Midbrain dopamine (DA) neurons respond to sensory cues that predict reward. We tested the hypothesis that projections from the pedunculopontine tegmental nucleus (PPTg) are involved in driving this DA cell activity. First, the activity of PPTg and DA neurons was compared in a cued-reward associative learning paradigm. The majority of PPTg neurons showed(More)
High-frequency stimulation of around 130 Hz delivered to the subthalamic nucleus (STN-DBS [deep brain stimulation]) is an effective treatment of Parkinson's disease (PD), but the mechanisms of its therapeutic effect remain obscure. Recently, it has been shown in anaesthetized rats that STN-DBS antidromically activates cortical neurons with coincident(More)
Striatal cholinergic interneurons, also known as tonically active neurons (TANs), acquire a pause in firing during learning of stimulus-reward associations. This pause response to a sensory stimulus emerges after repeated pairing with a reward. The conditioned pause is dependent on dopamine from the substantia nigra, but its underlying cellular mechanism is(More)
The striatum is the major input nucleus of the basal ganglia. It is thought to play a key role in learning on the basis of positive reinforcement and in action selection. One view of the striatum conceives it as comprising a reiterated matrix of processing units that perform common operations in different striatal regions, namely synaptic plasticity(More)
The concept of a motor program has been used to interpret a diverse range of empirical findings related to preparation and initiation of voluntary movement. In the absence of an underlying mechanism, its exploratory power has been limited to that of an analogy with running a stored computer program. We argue that the theory of cortical cell assemblies(More)
Extinction of behavior enables adaptation to a changing world and is crucial for recovery from disorders such as phobias and drug addiction. However, the brain mechanisms underlying behavioral extinction remain poorly understood. Midbrain dopamine (DA) neurons appear to play a central role in most acquisition processes of appetitive conditioning. Here, we(More)
We review strategies for developing animal models for examining and selecting compounds with potential therapeutic benefit in attention-deficit hyperactivity disorder (ADHD). ADHD is a behavioural disorder of unknown aetiology and pathophysiology. Current understanding suggests that genetic factors play an important role in the aetiology of ADHD. The(More)