, 2010, Goldberg and Reynolds, 2011, Morris et al., 2004, Raz et al., 1996 and Smith et al., 2004) and that show stereotyped burst activity on presentation of salient stimuli (Aosaki
et al., 1994 and Matsumoto et al., 2001). We directly tested the intriguing possibility that activation of intralaminar thalamic glutamate inputs to striatum might also drive DA release via a striatal nAChR-dependent mechanism. Indeed, laser activation of ChR2-eYFP-expressing thalamostriatal axons arising from intralaminar thalamus in CaMKII-Cre mice evoked DA release in coronal striatal slices, and this was prevented by nAChR inhibition and, necessarily, glutamate receptor antagonists but not GABA receptor antagonists (Figure 4; n = 4 animals, TTX-sensitive, Ca2+-dependent). ACh-dependent DA signals can Selleckchem MG-132 therefore be driven by the thalamic inputs that synchronize activity in ChIs in vivo. It is interesting in this regard that the relatively “digital” nature of the stereotyped burst activity in the thalamostriatal network that is associated with salient event detection parallels the lack of simple frequency dependence in the ChI activation of DA release seen here. In any event, these data suggest that DA may be important for conveying
salience- or attention-related signals mediated not through changes in DA neuron firing but through activation Selleckchem Ribociclib of DA axons by ChIs and their inputs. Third, we would expect that a ChI-driven DA signal will have key outcomes for DA functions that are encoded by dynamic patterns of activity until in DA neurons themselves. The outcome will depend entirely on the timing of activity in DA neurons relative to ChIs. Pauses in ChIs have been suggested previously to remove a low-pass filter on
DA release during concurrent changes in DA neuron activity (Cragg, 2006). Prior ChI-driven DA release could shunt (limit) the impact of subsequent changes in DA neuron activity, while alternatively, postpause “rebound” facilitation in ChI activity (Aosaki et al., 1995, Apicella, 2007 and Morris et al., 2004), which probably corresponds to increased synchrony in the population, could critically supplement preceding DA signals and promote, for example, the selection of a behavior. In addition, discrete functions for DA could be driven by synchronous activity in ChIs despite an absence of accompanying phasic changes in DA neuron activity, which otherwise would be taken as evidence for functions not requiring phasic DA. Furthermore, what might be the outcome for nicotine action? By desensitizing nAChRs on DA axons, nicotine would be expected to prevent ChI-driven DA release (pilot observations suggest this to be the case, data not shown) and thereby devolve the control of DA release to activity in DA neurons without modulation by ChIs. In this case, DA release might be a more direct reporter of activity in DA neurons than with nAChRs active (Rice and Cragg, 2004).