An electrophysiological investigation of the extrinsic modulation of ventral pallidum neurons by dopamine and serotonin

Abstract

The ventral pallidum (VP) is a key output structure of the basal ganglia and has multiple
connections with cortical and limbic regions. The VP is modulated by extrinsic
neurotransmitters, including dopamine and serotonin, but the cellular mechanisms
underlying this modulation are only partially understood. This thesis describes an in
vitro electrophysiological investigation of such extrinsic modulation employing
extracellular multi electrode recordings of the VP and pharmacological manipulations.
Our data provide novel information on how dopamine modulates VP neurons acting
both pre- and post-synaptically. Presynaptic excitatory effects of dopamine are mediated
by D1-like and D2-like receptors, through effects on glutamate release and subsequently
ionotropic and metabotropic glutamate receptor activation. Postsynaptic, direct effects
are mediated by D2-like receptors and induce decreases in firing frequency within the
VP. Our data identifies two populations of neurons in the VP, which can be consistently
separated by their spike half-width profile and their responses to D2-like receptor
agonists.
With regard to serotonin, both excitatory and inhibitory responses to its application
were observed in the VP. Our data suggests that excitatory effects of Serotonin (5HT)
are presynaptic, while the inhibitory responses to 5HT are postsynaptic, direct effects.
Our data also suggest that 5HT1a, 5HT5A and 5HT7 receptors are responsible for
increases in firing frequency to 5HT application and 5-HT2c receptors are likely
candidates for the decrease in firing frequency to 5HT application in the VP.
We also investigated the effects of electric activation of NAc inputs to the VP. Our data
are consistent with the literature, showing that NAc inputs inhibit VP neurons.
Overall, these results cast light on the cellular mechanism by which dopamine and
serotonin modulate VP neurons and have important implications for our understanding
of the role the VP plays in reward processing and related dysfunctions.