Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 21, Pages 5504-5512Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5493-07.2008
Keywords
striatum; GABA; medium spiny neurons; lateral inhibition; patch clamp; Parkinson's disease
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Funding
- NIMH NIH HHS [P50 MH074866-01, P50 MH074866, MH 074866] Funding Source: Medline
- NINDS NIH HHS [NS 34696, R37 NS034696, R01 NS034696, R01 NS034696-16] Funding Source: Medline
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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 D-1 or D-2 dopamine receptor expression was reported with EGFP (enhanced green fluorescent protein). These studies revealed that unidirectional connections were common between both D-1 receptor-expressing MSN (D-1 MSN) pairs (26%) and D-2 receptor-expressing MSN (D-2 MSN) pairs (36%). D2 MSNs also commonly formed synapses on D-1 MSNs (27% of pairs). Conversely, only 6% of the D-1 MSNs formed detectable connections with D-2 MSNs. Furthermore, synaptic connections formed by D-1 MSNs were weaker than those formed by D-2 MSNs, a difference that was attributable to fewer GABA(A) receptors at D-1 MSN synapses. The strength of detectable recurrent connections was dramatically reduced in Parkinson's disease models. The studies demonstrate that recurrent collateral connections between MSNs are not random but rather differentially couple D-1 and D-2 MSNs. Moreover, this recurrent collateral network appears to be disrupted in Parkinson's disease models, potentially contributing to pathological alterations in MSN activity patterns and psychomotor symptoms.
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