Article

Mesocortical dopamine neurons operate in distinct temporal domains using multimodal signaling. J Neurosci

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: 6.75). 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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    • "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.
    Brain Structure and Function 11/2014; DOI:10.1007/s00429-014-0950-2 · 4.57 Impact Factor
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    • "Further tests suggested that this transmitter was probably coreleased by the dopaminergic terminals in cortex and not released from glutamatergic projection neurons in the ventral tegmental area (Lavin et al. 2005). Lavin et al. (2005) also found evidence that the following inhibitory potential was mediated by GABA. Because of the large similarities of the electrically evoked responses in the auditory cortex, the somatosensory cortex, the superior temporal polysensory cortex (this study), and prefrontal cortex (e.g., Lavin et al. 2005; Watanabe et al. 2009), we consider that the electrically evoked responses in sensory cortex are also generated by glutamate that is coreleased from the dopaminergic terminals and by subsequent GABA-mediated inhibition. "
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    ABSTRACT: Motivated by the increasing evidence that auditory cortex is under control of dopaminergic cell structures of the ventral midbrain, we studied how the ventral tegmental area and substantia nigra affect neuronal activity in auditory cortex. We electrically stimulated 567 deep brain sites in total within and in the vicinity of the two dopaminergic ventral midbrain structures and at the same time, recorded local field potentials and neuronal discharges in cortex. In experiments conducted on three awake macaque monkeys, we found that electrical stimulation of the dopaminergic ventral midbrain resulted in short-latency (~35 ms) phasic activations in all cortical layers of auditory cortex. We were also able to demonstrate similar activations in secondary somatosensory cortex and superior temporal polysensory cortex. The electrically evoked responses in these parts of sensory cortex were similar to those previously described for prefrontal cortex. Moreover, these phasic responses could be reversibly altered by the dopamine D1-receptor antagonist SCH23390 for several tens of minutes. Thus, we speculate that the dopaminergic ventral midbrain exerts a temporally precise, phasic influence on sensory cortex using fast-acting non-dopaminergic transmitters and that their effects are modulated by dopamine on a longer timescale. Our findings suggest that some of the information carried by the neuronal discharges in the dopaminergic ventral midbrain, such as the motivational value or the motivational salience, is transmitted to auditory cortex and other parts of sensory cortex. The mesocortical pathway may thus contribute to the representation of non-auditory events in the auditory cortex and to its associative functions.
    Brain Structure and Function 08/2014; DOI:10.1007/s00429-014-0855-0 · 4.57 Impact Factor
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    • "Thinner cryosections may resolve this contamination issue. Our lack of evidence for Vglut2 transcripts in microdissected dopamine neuron samples is somewhat surprising given the neuroanatomical [5] [12] [13], electrophysiological [14] [15], genetic/optogenetic [16] [17] [18], and behavioral reports [19], indicating that at least some midbrain dopamine neurons are capable of glutamate cotransmission (for review see [20]). However, the extent of dopamine and glutamate coexistence as neurotransmitters in midbrain dopamine neurons is limited , with SN being devoid of Vglut2 and dorsal striatum corelease [12] [17]. "
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    ABSTRACT: The ability to microdissect individual cells from the nervous system has enormous potential, as it can allow for the study of gene expression in phenotypically identified cells. However, if the resultant gene expression profiles are to be accurately ascribed, it is necessary to determine the extent of contamination by nontarget cells in the microdissected sample. Here, we show that midbrain dopamine neurons can be laser-microdissected to a high degree of enrichment and purity. The average enrichment for tyrosine hydroxylase (TH) gene expression in the microdissected sample relative to midbrain sections was approximately 200-fold. For the dopamine transporter (DAT) and the vesicular monoamine transporter type 2 (Vmat2), average enrichments were approximately 100- and 60-fold, respectively. Glutamic acid decarboxylase (Gad65) expression, a marker for GABAergic neurons, was several hundredfold lower than dopamine neuron-specific genes. Glial cell and glutamatergic neuron gene expression were not detected in microdissected samples. Additionally, SN and VTA dopamine neurons had significantly different expression levels of dopamine neuron-specific genes, which likely reflects functional differences between the two cell groups. This study demonstrates that it is possible to laser-microdissect dopamine neurons to a high degree of cell purity. Therefore gene expression profiles can be precisely attributed to the targeted microdissected cells.
    07/2013; 2013:747938. DOI:10.1155/2013/747938
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