Spatiotemporal characterization of corticolimbic dopamine and noradrenaline signaling and affective state modulation by mfb stimulation

Deep brain stimulation (DBS) of the medial forebrain bundle (mfb DBS) shows promise for treating psychiatric disorders, but the neurochemical mechanisms behind its effects are still unclear. In a study using adult Sprague Dawley rats, researchers utilized fiber photometry to monitor mfb DBS-evoked dopamine (DA) and noradrenaline (NA) signaling in the nucleus accumbens (NAc) and prefrontal cortex (PFC) under various stimulation patterns, laterality conditions, and prolonged stimulation paradigms. Simultaneously, ultrasonic vocalizations (USVs) were recorded to gauge behavioral responses.

The findings revealed that bilateral mfb DBS led to a significant increase in catecholaminergic signals in both the NAc and PFC compared to sham stimulation. The size and timing of these responses were more influenced by the stimulation pattern than laterality, with longer pulse widths generally resulting in the most substantial effects. Importantly, the timing of catecholaminergic signaling remained elevated throughout the 10-minute stimulation period, with the NAc DA exhibiting the most sustained response.

Moreover, mfb DBS stimulated an increase in USV calls and peak frequencies, indicating an enhancement in positive affective states. However, there was no consistent correlation between the magnitude of catecholaminergic signals and these behavioral changes. This suggests that the relationship between acute USV responses and regional catecholamine signaling is more complex than initially thought.

In conclusion, the study demonstrates that mfb DBS engages catecholaminergic signaling in a parameter-dependent and region-specific manner, with stimulation patterns playing a crucial role in downstream circuit engagement. While the impact of mfb DBS on positive-affective USV output is evident, further research is needed to elucidate the intricate relationship between acute USV responses and regional catecholamine signaling.