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


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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    ABSTRACT: The ventral tegmental area (VTA) is an evolutionarily conserved structure that has roles in reward-seeking, safety-seeking, learning, motivation, and neuropsychiatric disorders such as addiction and depression. The involvement of the VTA in these various behaviors and disorders is paralleled by its diverse signaling mechanisms. Here we review recent advances in our understanding of neuronal diversity in the VTA with a focus on cell phenotypes that participate in 'multiplexed' neurotransmission involving distinct signaling mechanisms. First, we describe the cellular diversity within the VTA, including neurons capable of transmitting dopamine, glutamate or GABA as well as neurons capable of multiplexing combinations of these neurotransmitters. Next, we describe the complex synaptic architecture used by VTA neurons in order to accommodate the transmission of multiple transmitters. We specifically cover recent findings showing that VTA multiplexed neurotransmission may be mediated by either the segregation of dopamine and glutamate into distinct microdomains within a single axon or by the integration of glutamate and GABA into a single axon terminal. In addition, we discuss our current understanding of the functional role that these multiplexed signaling pathways have in the lateral habenula and the nucleus accumbens. Finally, we consider the putative roles of VTA multiplexed neurotransmission in synaptic plasticity and discuss how changes in VTA multiplexed neurons may relate to various psychopathologies including drug addiction and depression.
    Full-text · Article · Jan 2016 · Journal of chemical neuroanatomy
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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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    ABSTRACT: In the nucleus accumbens (NAc), dopamine transmission modulates glutamatergic input from the prefrontal cortex (PFC). This neuromodulatory action of dopamine can be disrupted by repeated exposure to psychostimulants such as cocaine. However, it is unclear whether this modulation depends on the precise timing of transmission at the same medium spiny neurons (MSNs) and if so, then whether this timing related modulation is also influenced by cocaine experience. Here, combining cocaine self-administration and in vivo extracellular recordings in anesthetized rats, we show that dopamine efflux in the NAc evoked by electrically stimulating the ventral tegmental area (VTA) exerted timing-dependent regulation of the excitatory accumbens' response to stimulation of the medial prefrontal cortex (mPFC), and that this modulation was also blunted following prolonged abstinence from cocaine self-administration. These data indicate that dopaminergic timing-dependent dysregulation of mPFC-NAc glutamatergic transmission is implicated in cocaine addiction and might contribute to vulnerability to drug relapse after prolonged abstinence. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Mar 2015 · Physiology & Behavior
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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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    ABSTRACT: This study shows that ongoing electrical stimulation of the dopaminergic ventral midbrain can modify neuronal activity in the auditory cortex of awake primates for several seconds. This was reflected in a decrease of the spontaneous firing and in a bidirectional modification of the power of auditory evoked potentials. We consider that both effects are due to an increase in the dopamine tone in auditory cortex induced by the electrical stimulation. Thus, the dopaminergic ventral midbrain may contribute to the tonic activity in auditory cortex that has been proposed to be involved in associating events of auditory tasks (Brosch et al. Hear Res 271:66-73, 2011) and may modulate the signal-to-noise ratio of the responses to auditory stimuli.
    Full-text · Article · Nov 2014 · Brain Structure and Function
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