Abstract
Neurons in many brain regions exhibit spontaneous, intrinsic rhythmic firing activity. This rhythmic firing activity may determine the way in which these neurons respond to extrinsic synaptic inputs. We hypothesized that neurons should be most responsive to inputs at the frequency of the intrinsic oscillation frequency. We addressed this question in the ventral tegmental area (VTA), a dopaminergic nucleus in the midbrain. VTA neurons have a unique propensity to exhibit spontaneous intrinsic rhythmic activity in the 1–5 Hz frequency range, which persists in the in-vitro brain slice, and form a network of weakly coupled oscillators. Here, we combine in-vitro simultaneous recording of action potentials from a 60 channel multi-electrode-array with cell-type-specific optogenetic stimulation of the VTA dopamine neurons. We investigated how VTA neurons respond to wide-band stochastic (Poisson input) as well as regular laser pulses. Strong synchrony was induced between the laser input and the spike timing of the neurons, both for regular pulse trains and Poisson pulse trains. For rhythmically pulsed input, the neurons demonstrated resonant behavior with the strongest phase locking at their intrinsic oscillation frequency, but also at half and double the intrinsic oscillation frequency. Stochastic Poisson pulse stimulation provided a more effective stimulation of the entire population, yet we observed resonance at lower frequencies (approximately half the oscillation frequency) than the neurons' intrinsic oscillation frequency. The non-linear filter characteristics of dopamine neurons could allow the VTA to predict precisely timed future rewards based on past sensory inputs, a crucial component of reward prediction error signaling. In addition, these filter characteristics could contribute to a pacemaker role for the VTA in synchronizing activity with other regions like the prefrontal cortex and the hippocampus.
Highlights
The ventral tegmental area (VTA) is a dopamine nucleus in the midbrain, alongside the substantia nigra and the red nucleus
In previous work we have shown that the spontaneous activity of the lateral dopamine neurons is highly rhythmical and variation in regularity did not lead to separable neuronal populations
Optogenetic stimulation using laser pulses affected the timing of the spikes
Summary
The ventral tegmental area (VTA) is a dopamine nucleus in the midbrain, alongside the substantia nigra and the red nucleus. VTA dopamine neurons have direct synaptic connections between each other but they connect through a local interneuron network (Bayer and Pickel, 1990; Omelchenko and Sesack, 2009). In addition they are likely to interact through dopamine volume transmission (Cragg et al, 2001). This phenomenon implies that the firing neurons create an oscillating extracellular dopamine concentration that results in auto inhibition of the population and helps to synchronize all neurons (van der Velden et al, 2017). The VTA network can be considered as a network of weakly coupled oscillators
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