Dopamine Excites Fast-Spiking Interneurons in the Striatum

Abstract

The striatum is the main recipient of dopaminergic innervation. Striatal projection neurons are controlled by cholinergic and GABAergic interneurons. The effects of dopamine on projection neurons and cholinergic interneurons have been described. Its action on GABAergic interneurons, however, is still unknown. We studied the effects of dopamine on fast-spiking (FS) GABAergic interneurons in vitro, with intracellular recordings. Bath application of dopamine elicited a depolarization accompanied by an increase in membrane input resistance (an effect that persisted in the presence of tetrodotoxin) and action-potential discharge. These effects were mimicked by the D1-like dopamine receptor agonist SKF38393 but not by the D2-like agonist quinpirole. Evoked corticostriatal glutamatergic synaptic currents were not affected by dopamine. Conversely, GABAergic currents evoked by intrastriatal stimulation were reversibly depressed by dopamine and D2-like, but not D1-like, agonists. Cocaine elicited effects similar to those of dopamine on membrane potential and synaptic currents. These results show that endogenous dopamine exerts a dual excitatory action on FS interneurons, by directly depolarizing them (through D1-like receptors) and by reducing their synaptic inhibition (through presynaptic D2-like receptors).

Dopaminergic modulation of short-term synaptic plasticity at striatal inhibitory synapses

“…Dopamine agonists depolarize FS interneurons in the striatum by D 1 -class receptors (61). However, in most cases, we did not observe a presynaptic modulation by the D 1 -agonist (FS3SPN) (32).…”

Dopaminergic Modulation of Axon Collaterals Interconnecting Spiny Neurons of the Rat Striatum

“…A lack of consistency in the action of dopaminergic drugs on intrastriatally evoked inhibition, as recorded in spiny cells, has been reported previously (Delgado et al, 2000;Fitzpatrick et al, 2001) and probably results from a great variety of dopaminergic actions on a diverse array of GABAergic terminals and interneurons targeting spiny cells (Lenz et al, 1994;Pisani et al, 2000;Momiyama and Koga, 2001;Bracci et al, 2002;Yasumoto et al, 2002;Centonze et al, 2003;Gao et al, 2003). When none of these actions predominate over the others in most trials, inconsistent effects should be seen.…”

“…The latter responses are likely to be variable because they come from a mixed source of GABAergic terminals: several classes of interneurons and recurrent axon collaterals (Kita, 1993;Jaeger et al, 1994;Kawaguchi et al, 1995;Koos and Tepper, 1999;Fitzpatrick et al, 2001). In case all interneuron types do not respond in the same manner to different classes of dopamine receptor agonists (Aosaki et al, 1998;Bracci et al, 2002;Centonze et al, 2002Centonze et al, , 2003Yasumoto et al, 2002;Gao et al, 2003), it is expected that variety will make this mixed source inconsistent when responding to the agonists. In contrast, if antidromic stimulation from the pallidum evokes IPSCs from a single source (i.e., axon collaterals), then the responses in this case are likely to be more consistent.…”

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

“…Favoring the second option is the report that, after binding to D 2 receptors, dopamine can be internalized to form a signaling complex (including ß‐arrestin and protein phosphatase 2) that regulates the Akt pathway (Beaulieu et al, 2008), a cascade involved in neuroprotection (Dudek et al, 1997; Soler et al, 1999). Dopamine inhibits GABA A ‐mediated synaptic inputs to intrinsic striatal neurons (Bracci, Centonze, Bernardi, & Calabresi, 2002; Momiyama & Koga, 2001; Pisani, Bonsi, Centonze, Calabresi, & Bernardi, 2000) through presynaptic D 2 receptors (Centonze et al, 2003; for a review, see Berke, 2011). All together, we speculate that dopamine could be involved in the acute and chronic protection of FS striatal terminals and, therefore, could contribute to long‐term FS survival.…”