Elsevier

Neuroscience

Volume 166, Issue 3, 31 March 2010, Pages 808-818
Neuroscience

Cellular Neuroscience
Research Paper
Subthalamic nucleus evokes similar long lasting glutamatergic excitations in pallidal, entopeduncular and nigral neurons in the basal ganglia slice

https://doi.org/10.1016/j.neuroscience.2010.01.011Get rights and content

Abstract

The subthalamic nucleus (STN) modulates the activity of globus pallidus (GP), entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr) neurons via its direct glutamatergic projections. To investigate the mechanism by which STN affects activity in these structures and whether STN induced activity is comparable among STN target neurons, we performed patch clamp recordings in a tilted, parasagittal, basal ganglia slice (BGS) that preserves these functional connections. We report that single, brief stimulation of the STN generates a brief monosynaptic AMPA-mediated excitatory postsynaptic current (EPSC) in GP, EP and SNr neurons. A higher intensity, supra-threshold activation evokes a compound EPSC consisting of an early monosynaptic component followed by a slow inward NMDA-mediated current with an overlying barrage of AMPA-mediated EPSCs. These late EPSCs were polysynaptic and gave rise to bursts of spikes that lasted several hundreds of milliseconds. They were eliminated by surgical removal of the STN from the BGS slice, indicating that the STN is required for their generation. Reconstruction of biocytin-filled STN neurons revealed that a third of STN neurons project intra-STN axon collaterals that may underlie polysynaptic activity. We propose that activation of the STN yields comparable long lasting excitations in its target neurons by means of a polysynaptic network.

Section snippets

Experimental procedures

C57/Bl6 mice aged postnatal days 14–29 were sacrificed by decapitation under halothane anesthesia and 400 μm-thick oblique parasagittal slices were cut with an angle of 10±2° to obtain BGS as previously described (Beurrier et al., 2006). For the slicing procedure, the solution contained (in mM) 110 choline, 2.5 KCl, 1.25 NaH2PO4, 7 MgCl2, 0.5 CaCl2, 25 NaHCO3, 7 glucose. After a recovery period, slices were moved to a submersion-type chamber in which recordings were made at room temperature

Results

To study the STN efferent pathways in isolation, we blocked GABAA receptors by the continuous application of Gabazine (10 μM) in order to eliminate GABAergic currents that were sometimes concomitant to the glutamatergic ones, mainly due to recurrent GABAergic axon collaterals between GP (Sadek et al., 2007) and SNr (Deniau et al., 1982) neurons.

Discussion

The present study in the BGS in vitro shows that STN stimulation evokes long lasting, compound EPSCs in GP neurons (type A and B), in EP neurons (type I and II) and in GABAergic SNr neurons. GP and EP responses shared striking similarities between them and with those recorded in SNr neurons in the present and previous (Shen and Johnson, 2006) studies. In all of the different types of target neurons recorded, compound EPSCs consisted of an initial AMPA-mediated EPSC followed by a barrage of

Acknowledgments

This work was supported by Institut National de la Santé et de la Recherche médicale (Inserm), Centre National de Recherche Scientifique (CNRS), and grants from Association France Parkinson and ERA-Net Neuron (PhysDBS). RA was supported by a PhD grant from the Ministère de la recherche (MRT) and Fondation pour la Recherche Médicale (FRM).

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