Recurrent collateral connections of striatal medium spiny neurons are disrupted in models of Parkinson's disease.
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%). D(2) 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.
Taverna
Stefano
S
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Ilijic
Ema
E
Surmeier
D James
DJ
D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D049229:Dendritic Spines / Q000473:pathology*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008474:Medial Forebrain Bundle / Q000293:injuries; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000473:pathology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011810:Quinoxalines / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D013565:Sympatholytics / Q000633:toxicity; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; C485184:enhanced green fluorescent protein; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine