Functional interconnectivity between the globus pallidus and the subthalamic nucleus in the mouse brain slice

• Published in: The Journal of physiology 2005-09, Vol.567 (3), p.977-987
• Main Authors: Loucif, K. C., Wilson, C. L., Baig, R., Lacey, M. G., Stanford, I. M.
• Format: Article
• Language: English
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Action Potentials - physiology; Animals; Apamin - pharmacology; Electric Stimulation; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - physiology; gamma-Aminobutyric Acid - metabolism; Globus Pallidus - drug effects; Globus Pallidus - physiology; Glutamic Acid - metabolism; In Vitro Techniques; Lysine - analogs & derivatives; Male; Mice; Mice, Inbred Strains; N-Methylaspartate - pharmacology; Nerve Net - physiology; Neurons - physiology; Picrotoxin - pharmacology; Subthalamic Nucleus - physiology; Tissue, System and Organ Physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2005.093807

In accordance with its central role in basal ganglia circuitry, changes in the rate of action potential firing and pattern of activity in the globus pallidus (GP)–subthalamic nucleus (STN) network are apparent in movement disorders. In this study we have developed a mouse brain slice preparation that maintains the functional connectivity between the GP and STN in order to assess its role in shaping and modulating bursting activity promoted by pharmacological manipulations. Fibre-tract tracing studies indicated that a parasagittal slice cut 20 deg to the midline best preserved connectivity between the GP and the STN. IPSCs and EPSCs elicited by electrical stimulation confirmed connectivity from GP to STN in 44/59 slices and from STN to GP in 22/33 slices, respectively. In control slices, 74/76 (97%) of STN cells fired tonically at a rate of 10.3 ± 1.3 Hz. This rate and pattern of single spiking activity was unaffected by bath application of the GABA A antagonist picrotoxin (50 μ m , n = 9) or the glutamate receptor antagonist (6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) 10 μ m , n = 8). Bursting activity in STN neurones could be induced pharmacologically by application of NMDA alone (20 μ m , 3/18 cells, 17%) but was more robust if NMDA was applied in conjunction with apamin (20–100 n m , 34/77 cells, 44%). Once again, neither picrotoxin (50 μ m , n = 5) nor CNQX (10 μ m , n = 5) had any effect on the frequency or pattern of the STN neurone activity while paired STN and GP recordings of tonic and bursting activity show no evidence of coherent activity. Thus, in a mouse brain slice preparation where functional GP–STN connectivity is preserved, no regenerative synaptically mediated activity indicative of a dynamic network is evident, either in the resting state or when neuronal bursting in both the GP and STN is generated by application of NMDA/apamin. This difference from the brain in Parkinson's disease may be attributed either to insufficient preservation of cortico-striato-pallidal or cortico-subthalamic circuitry, and/or an essential requirement for adaptive changes resulting from dopamine depletion for the expression of network activity within this tissue complex.