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The article focuses on emerging role of astrocytes in striatal synaptic plasticity. Topics include the region of particular interest to those who study action selection and movement control is the striatum, which is the major input nucleus of the basal ganglia, and the testimony to its importance, the striatum is implicated in many neurological and psychiatric diseases such as Parkinson's disease and obsessive-compulsive disorder.

The late phase of long-term potentiation (LTP) at glutamatergic synapses, which is thought to underlie long-lasting memory, requires gene transcription in the nucleus. However, the mechanism by which signaling initiated at synapses is transmitted into the nucleus to induce transcription has remained elusive. Here, we found that induction of LTP in only three to seven dendritic spines in rat CA1 pyramidal neurons was sufficient to activate extracellular signal-regulated kinase (ERK) in the nucleus and regulate downstream transcription factors. Signaling from individual spines was integrated over a wide range of time (>30 minutes) and space (>80 micrometers). Spatially dispersed inputs over multiple branches activated nuclear ERK much more efficiently than clustered inputs over one branch. Thus, biochemical signals from individual dendritic spines exert profound effects on nuclear signaling. [ABSTRACT FROM AUTHOR]

Levodopa-induced dyskinesia (LID) poses a significant health care challenge for Parkinson's disease (PD) patients. Amantadine is currently the only drug proven to alleviate LID. Although its efficacy in treating LID is widely assumed to be mediated by blockade of N-methyl-D-aspartate (NMDA) glutamate receptors, our experiments demonstrate that at therapeutically relevant concentrations, amantadine preferentially blocks inward-rectifying K+ channel type 2 (Kir2) channels in striatal spiny projection neurons (SPNs) - not NMDA receptors. In so doing, amantadine enhances dendritic integration of excitatory synaptic potentials in SPNs and enhances - not antagonizes - the induction of long-term potentiation (LTP) at excitatory, axospinous synapses. Taken together, our studies suggest that the alleviation of LID in PD patients is mediated by diminishing the disparity in the excitability of direct- and indirect-pathway SPNs in the on state, rather than by disrupting LTP induction. This insight points to a pharmacological approach that could be used to effectively ameliorate LID and improve the quality of life for PD patients. [ABSTRACT FROM AUTHOR]