Article

Lavin, A. et al. Mesocortical dopamine neurons operate in distinct temporal domains using multimodal signaling. J. Neurosci. 25, 5013-5023

Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 05/2005; 25(20):5013-23. DOI: 10.1523/JNEUROSCI.0557-05.2005
Source: PubMed

ABSTRACT

In vivo extracellular recording studies have traditionally shown that dopamine (DA) transiently inhibits prefrontal cortex (PFC) neurons, yet recent biophysical measurements in vitro indicate that DA enhances the evoked excitability of PFC neurons for prolonged periods. Moreover, although DA neurons apparently encode stimulus salience by transient alterations in firing, the temporal properties of the PFC DA signal associated with various behaviors is often extraordinarily prolonged. The present study used in vivo electrophysiological and electrochemical measures to show that the mesocortical system produces a fast non-DA-mediated postsynaptic response in the PFC that appears to be initiated by glutamate. In contrast, short burst stimulation of mesocortical DA neurons that produced transient (<4 s) DA release in the PFC caused a simultaneous reduction in spontaneous firing (consistent with extracellular in vivo recordings) and a form of DA-induced potentiation in which evoked firing was increased for tens of minutes (consistent with in vitro measurements). We suggest that the mesocortical system might transmit fast signals about reward or salience via corelease of glutamate, whereas the simultaneous prolonged DA-mediated modulation of firing biases the long-term processing dynamics of PFC networks.

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Available from: Antonieta Lavin, Mar 04, 2015
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    • "The GABAergic neurons of the tVTA/RMTg provide a major inhibitory control to VTA DAergic neurons (Kaufling et al., 2010;Matsui and Williams, 2011). In addition to VTA DAergic and GABAergic neurons, early electrophysiological studies of the midbrain suggested the possibility of glutamatergic signaling by some VTA neurons (Wilson et al., 1982;Mercuri et al., 1985;Sulzer et al., 1998;Joyce and Rapport, 2000;Chuhma et al., 2004;Ungless et al., 2004;Lavin et al., 2005;Chuhma et al., 2009). Anatomical identification of glutamatergic neurons has recently become possible due to the cloning of three distinct vesicular glutamate transporters (VGluT1, VGluT2, and VGluT3;Bellocchio et al., 1998;Bai et al., 2001;Fremeau et al., 2001Fremeau et al., , 2002Fujiyama et al., 2001;Hayashi et al., 2001;Herzog et al., 2001;Takamori et al., 2000;Varoqui et al., 2002;Gras et al., 2002). "
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    • "First, we utilized a single-pulse stimulus, instead of the traditionally used train stimulation, to stimulate the VTA in efforts to examine the timing-dependent effects of dopamine efflux (and not necessarily phasic dopamine release) on mPFC–NAc transmission. Several lines of evidence indicate that a single-pulse electrical stimulation can activate dopamine neuronal firing or evoke dopamine release [30] [38]. Furthermore , the 100 ms pairing interval between the mPFC and VTA stimulations was selected on the basis of a previous study, in which a 200 ms interval was used but with train stimulation of the VTA [5], together with the known extracellular half-life of electrically-evoked dopamine release (less than 50–60 ms) [13]. "
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    • "In our first experiments, we adopted the paradigm that has been successfully used in studying the dopaminergic mesocortical pathway in rodents (e.g., Lavin et al. 2005). We mimicked the activation of the dopaminergic ventral midbrain by applying brief electrical stimulation trains to the ventral tegmental area and to the substantia nigra and assessed the effects on auditory cortex by measuring neuronal activity in cortex. "
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