Abstract
Medium spiny neurons (MSNs) of the dorsal striatum represent the first relay of cortico–striato–thalamic loop, responsible for the initiation of voluntary movements and motor learning. GABAergic transmission exerts the main inhibitory control of MSNs. However, MSNs also express chloride-permeable glycine receptors (GlyRs) although their subunit composition and functional significance in the striatum is unknown. Here, we studied the function of GlyRs in MSNs of young adult mice. We show that MSNs express functional GlyRs, with α2 being the main agonist binding subunit. These receptors are extrasynaptic and depolarizing at resting state. The pharmacological inhibition of GlyRs, as well as inactivation of the GlyR α2 subunit gene hyperpolarize the membrane potential of MSNs and increase their action potential firing offset. Mice lacking GlyR α2 showed impaired motor memory consolidation without any changes in the initial motor performance. Taken together, these results demonstrate that tonically active GlyRs regulate the firing properties of MSNs and may thus affect the function of basal ganglia.
Highlights
The striatum is the primary input site of the basal ganglia, a set of brain nuclei, important for voluntary movements and motor learning (Graybiel, 2008; Doyon et al, 2009)
Active Glycine Receptors Are Present in Medium spiny projection neurons (MSNs) of the Dorsal Striatum
We found that 91 ± 2.5% of CTIP2-positive cells co-localized with glycine receptors (GlyRs) signal, which confirmed the expression of GlyRs by MSNs
Summary
The striatum is the primary input site of the basal ganglia, a set of brain nuclei, important for voluntary movements and motor learning (Graybiel, 2008; Doyon et al, 2009) It collects the incoming information from cortical areas in order to build motor patterns based on the current environmental situation and past experience. Striatonigral (STN) MSNs innervate the substantia nigra pars reticulata and the internal segment of the globus pallidus (or entopeduncular nucleus in rodents). Activation of this pathway leads to disinhibition of the basal ganglia output structures and participates in initiation of voluntary movement. Striatopallidal (STP) MSNs innervate the external globus pallidus, which inversely controls the same thalamo-cortical motor circuits and inhibits competing movements during the realization of the motor task
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