Subregion-specific modulation of excitatory input and dopaminergic output in the striatum by tonically activated glycine and GABAA receptors

Abstract

The flow of cortical information through the basal ganglia is a complex spatiotemporal pattern of increased and decreased firing. The striatum is the biggest input nucleus to the basal ganglia and the aim of this study was to assess the role of inhibitory GABA A and glycine receptors in regulating synaptic activity in the dorsolateral striatum (DLS) and ventral striatum (nucleus accumbens, nAc). Local field potential recordings from coronal brain slices of juvenile and adult Wistar rats showed that GABA A receptors and strychninesensitive glycine receptors are tonically activated and inhibit excitatory input to the DLS and to the nAc. Strychnine-induced disinhibition of glutamatergic transmission was insensitive to the muscarinic receptor inhibitor scopolamine (10 μM), inhibited by the nicotinic acetylcholine receptor antagonist mecamylamine (10 μM) and blocked by GABA A receptor inhibitors, suggesting that tonically activated glycine receptors depress excitatory input to the striatum through modulation of cholinergic and GABAergic neurotransmission. As an end-product example of striatal GABAergic output in vivo we measured dopamine release in the DLS and nAc by microdialysis in the awake and freely moving rat. Reversed dialysis of bicuculline (50 μM in perfusate) only increased extrasynaptic dopamine levels in the nAc, while strychnine administered locally (200 μM in perfusate) decreased dopamine output by 60% in both the DLS and nAc. Our data suggest that GABA A and glycine receptors are tonically activated and modulate striatal transmission in a partially subregion-specific manner.

The Glycine Receptor—A Functionally Important Primary Brain Target of Ethanol

“…Further, in vivo microdialysis studies suggest that extracellular DA levels in nAc are tonically sustained by GlyRs, since reversed microdialysis of strychnine concentration dependently reduces DA levels, an effect prevented by coperfusion with glycine and reversed when strychnine perfusion is terminated (Molander and Söderpalm, ). Thus, GlyRs in the nAc are tonically activated, which was observed also in recent field‐potential studies in vitro (Adermark et al., ,b). Reports on tentative effects of EtOH on extracellular glycine levels in the CNS are few, where most have failed to observe any effect (Dahchour et al., ; Smith et al., ), whereas 1 group found a trend for a slight increase in glycine levels in nAc after local EtOH perfusion (Adermark et al., ,b).…”

“…Thus, GlyRs in the nAc are tonically activated, which was observed also in recent field‐potential studies in vitro (Adermark et al., ,b). Reports on tentative effects of EtOH on extracellular glycine levels in the CNS are few, where most have failed to observe any effect (Dahchour et al., ; Smith et al., ), whereas 1 group found a trend for a slight increase in glycine levels in nAc after local EtOH perfusion (Adermark et al., ,b).…”

Nicotine produces chronic behavioral sensitization with changes in accumbal neurotransmission and increased sensitivity to re‐exposure

“…Coronal brain slices containing the striatal nucleus and the overlying cortex were prepared from nicotine‐ and vehicle‐treated rats, as previously described (Adermark et al . ). In brief, animals were anesthetized before decapitation; the brains were quickly dissected and submerged in ice‐cold modified aCSF, continuously bubbled with a mixture of 95 percent O 2 /5 percent CO 2 gas for 5 minutes before being sectioned coronally in 400‐μm‐thick slices.…”

Alterations in ethanol-induced accumbal transmission after acute and long-term zinc depletion

“…; Adermark et al . 2011a), where GlyR activity sustains DA levels (Molander & Soderpalm 2005b). Zn 2+ concentrations lower than 10 nM potentiates GlyR function, whereas higher concentrations instead inhibit GlyR function.…”

“…Coronal brain slices containing the striatal nucleus and the overlaying cortex were prepared from EtOH consuming Zn 2+ ‐deficient Wistar rats, EtOH‐consuming control animals or EtOH naïve rats, as previously described (Adermark et al . 2011a). In brief, animals were anesthetized before decapitation, and the brains were submerged in ice‐cold modified aCSF for 5 minutes before sectioned coronally in 400‐μm‐thick slices.…”