Mesostriatal dopamine neurons and striatal cholinergic interneurons (tonically active neurons, TANs) participate in signalling the behavioural or reward-related significance of stimuli in the environment. Both populations of neurons signal reward-related events by briefly modifying their firing frequencies in a synchronous but opposite manner. Furthermore, some form of antagonistic balance between dopamine and acetylcholine (ACh) is well known to regulate postsynaptic signal integration in striatum. Recent findings have revealed direct presynaptic ACh/dopamine interactions via nicotinic receptors that can play a key role in governing striatal dopamine signalling and that suggest that these synchronous changes in neuron activities may have key physiological implications. Striatal ACh appears to operate a powerful but complex neuromodulatory control over dopamine release probability via striatal nicotinic acetylcholine receptors (nAChRs) on dopamine axons. Tonic levels of striatal ACh at β2-subunit-containing (β2*)-nAChRs promote dopamine release by individual action potentials but, owing to accompanying short-term depression, minimize the subsequent release of dopamine by multiple action potentials in a high-frequency (or ‘reward-related’) burst (Rice and Cragg, 2004). Nicotine, at concentrations seen in smokers, desensitizes tonically active β2*-nAChRs and thus can reduce initial dopamine release probability but also consequently facilitate release by bursts thus enhancing the contrast in dopamine signals by high frequency, burst activity. In conjunction with the excitation of midbrain dopamine neurons, this filtering action offers a mechanism through which nicotine may promote how burst activity in dopamine neurons facilitates goal-directed behaviour and reinforcement processing. Here, using data obtained by monitoring action potential-dependent dopamine release in real-time using fast-scan cyclic voltammetry at carbon-fibre microelectrodes in rodent striatal slices, we consider the role of pauses in ACh interneuron activity on the presynaptic filtering of dopamine release by nicotinic receptors. We have explored the role of the different nAChR subtypes formed by the molecular subunit diversity expressed by dopamine neurons. Reductions in striatal ACh tone at nAChRs that might accompany pauses in TAN activity powerfully polarize how opposing dopamine neuron activities are transduced into dopamine release. Like nicotine, blockade of ACh tone at nAChRs powerfully enhances dopamine signals offered by reward-related bursts and diminishes dopamine signals released by tonic activity or pauses in dopamine neurons. These data suggest that reward-related dopamine signals could therefore be enhanced by the concomitant pause activity in TANs. Like nicotine, TAN pauses could powerfully enhance the contrast, or salience, of dopamine signals offered by reward-related bursts, and even by reward omission-related pauses, in dopamine neurons. Exploration of the nAChR subtypes responsible for this presynaptic filtering of dopamine release probability suggest key roles for α6β2 and for non-α6, β2-subunit containing nAChRs in this presynaptic filtering of dopamine release probability by endogenous ACh. Together these data reveal that endogenous ACh, acting at α6β2 and/or non-α6, β2-subunit containing nAChRs exerts a powerful presynaptic filter on dopamine signalling and that the concomitant changes in dopamine and ACh neuron activity that accompany reward-related information could act in concert to promote dopamine signalling (Cragg 2006). These functionally cooperative TAN-dopamine interactions within striatum may shed light on pharmacotherapies for addiction and parkinsonian disorders.