Jibran Khokhar (@drjkhokhar.bsky.social)

The Ventral Pallidum Innervates a Distinct Subset of Midbrain Dopamine Neurons Aberrant dopamine transmission is a hallmark of several psychiatric disorders. Dopamine neurons in the ventral tegmental area (VTA) display distinct activity states that are regulated by discrete afferent inputs. For example, burst firing requires excitatory input from the mesopontine tegmentum, while dopamine neuron population activity, defined as the number of spontaneously active dopamine neurons, is thought to be dependent on inhibitory drive from the ventral pallidum (VP). Rodent models used to study psychiatric disorders, such as psychosis, consistently exhibit elevated dopamine neuron population activity, due to decreased tonic inhibition from the VP. However, it remains unclear whether the VP can modulate all dopamine neurons or if only a specific subset of VTA dopamine neurons receive innervation from the VP to be recruited as required. This knowledge is critical for understanding dopamine regulation in normal and pathological conditions. Here, we used in vivo electrophysiology in male and female rats to record VTA dopamine neurons inhibited by electrical stimulation of the VP. Specifically, VP stimulation inhibited ∼22% of spontaneously active dopamine neurons; however, activation of the ventral hippocampus, a modulator of VTA population activity, increased the proportion to ∼48%. This increase suggests that VP selectively modulates a subset of dopamine neurons that can be recruited by afferent activation. Anterograde monosynaptic tracing revealed that approximately half of the VTA dopamine neurons receive input from the VP. Taken together, we demonstrate that a subset of VTA dopamine neurons receives monosynaptic input from the VP, providing valuable information regarding the regulation of VTA neuron activity. https://doi.org/10.1523/ENEURO.0222-25.2025