Fast transmission from the dopaminergic ventral midbrain to the sensory cortex of awake primates

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.

Tonic effects of the dopaminergic ventral midbrain on the auditory cortex of awake macaque monkeys

“…The AEP at latencies longer than 148 ms was not considered to avoid the electrical artifact in the EA_750 condition in which the electrical stimulation of the next trial was presented 150 ms after the onset of the noise burst of the present trial. The EA_0 condition was not analyzed for possible modulations of the AEP because we were not able to disentangle the electrically induced modulations from the direct interactions between the AEP and the electrically evoked potential (Mylius et al 2014), using an approach similar to the one used previously to assess interactions between two sequential tones (Brosch et al 1999). This is in contrast to the multiunit activity, for which we were able to analyze modulations of the driven firing in the EA_0 condition because only a few sites had overlapping electrically and auditory evoked firing (Mylius et al 2014).…”

“…Both monkeys were also used in our previous study (Mylius et al 2014). Since methods were mostly the same in both studies, we briefly summarize the common methods and describe in detail only the specific methods of the current report.…”

“…In Monkey I, stimulation electrodes were acutely placed into the dopaminergic ventral midbrain each day, using the methods and criteria adopted by Mylius et al (2014): (1) stereotactic planning with the aid of anatomical MRI scans of the monkey's brain and brain atlas coordinates; (2) physiologically identifiable landmarks such as red nucleus, which is located just before the dopaminergic ventral midbrain; (3) electrophysiological characteristics of neurons in the dopaminergic ventral midbrain; (4) the shape of the electrically evoked field potentials in auditory cortex.…”

“…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. With this approach, we have recently discovered that the dopaminergic ventral midbrain can affect neuronal activity in the auditory cortex on the time scale of subseconds (Mylius et al 2014). …”

“…This question was investigated by comparing spontaneous activity and auditory evoked activity in auditory cortex with and without the electrical stimulation of the dopaminergic ventral midbrain. Guided by our initial findings that the electrical stimulation could evoke short-latency and short-lasting phasic activations of auditory cortex (Mylius et al 2014), we considered that the effects of the dopaminergic ventral midbrain on the auditory cortex depended on the interval between the electrical stimulus and the auditory stimulus. Therefore, we tested three different pairings of the two stimuli.…”