Recurrent Collateral Connections of Striatal Medium Spiny Neurons Are Disrupted in Models of Parkinson's Disease

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Abstract
The principal neurons of the striatum, GABAergic medium spiny neurons (MSNs), are interconnected by local recurrent axon collateral synapses. Although critical to many striatal models, it is not clear whether these connections are random or whether they preferentially link functionally related groups of MSNs. To address this issue, dual whole patch-clamp recordings were made from striatal MSNs in brain slices taken from transgenic mice in which D1 or D2 dopamine receptor expression was reported with EGFP (enhanced green fluorescent protein). These studies revealed that unidirectional connections were common between both D1 receptor-expressing MSN (D1 MSN) pairs (26%) and D2 receptor-expressing MSN (D2 MSN) pairs (36%). D2 MSNs also commonly formed synapses on D1 MSNs (27% of pairs). Conversely, only 6% of the D1 MSNs formed detectable connections with D2 MSNs. Furthermore, synaptic connections formed by D1 MSNs were weaker than those formed by D2 MSNs, a difference that was attributable to fewer GABAA receptors at D1 MSN synapses. The strength of detectable recurrent connections was dramatically reduced in Parkinson9s disease models. The studies demonstrate that recurrent collateral connections between MSNs are not random but rather differentially couple D1 and D2 MSNs. Moreover, this recurrent collateral network appears to be disrupted in Parkinson9s disease models, potentially contributing to pathological alterations in MSN activity patterns and psychomotor symptoms.

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