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 GABAA 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 GABAA receptors and strychnine-sensitive 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 GABAA 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 GABAA and glycine receptors are tonically activated and modulate striatal transmission in a partially subregion-specific manner.
Highlights
In addition to the control of movements, the basal ganglia are involved in a variety of cognitive and mnemonic functions in the generation and execution of context dependent behaviors (Bolam et al, 2000)
GABAergic MODULATION OF EXCITATORY INPUT AND EXTRACELLULAR DOPAMINE LEVELS Synaptic transmission in the striatum is inhibited by two distinct GABAergic circuits; The feedforward circuit consisting of www.frontiersin.org
Even though GABAergic interneurons are outnumbered by medium spiny projection neurons (MSNs), feedforward inhibition appears to be more powerful with respect to the total number of synapses, the synaptic strength, and the net effect on the postsynaptic activity of the MSN (Tepper et al, 2008)
Summary
In addition to the control of movements, the basal ganglia are involved in a variety of cognitive and mnemonic functions in the generation and execution of context dependent behaviors (Bolam et al, 2000). The output of the basal ganglia is a complex spatiotemporal pattern of increased and decreased firing, which leads to an inhibitory output signal under resting conditions that is reduced during basal ganglia associated behavior (Chevalier and Deniau, 1990). Based on the subregion-specific extrinsic connections reaching the striatum and observations from behavioral studies the Abbreviations: EtOH, ethanol; nAc, nucleus accumbens; VTA, ventral tegmental area. Reward-guided learning is not solely controlled by the mesoaccumbens pathway arising from dopaminergic neurons in the ventral tegmental area (VTA) and projecting to the nAc, and involves the nigrostriatal pathway (Yin et al, 2008; Rushworth et al, 2009)
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