In Parkinson’s disease the neurones of the subthalamic nucleus (STN) show increased synchrony and oscillatory burst discharge, probably reflecting a breakdown of parallel processing in basal ganglia (BG) circuitry. To understand better the mechanisms underlying this transition, we sought to mimic this change in firing pattern within sagittal slices of midbrain taken from humanely killed rats, at 32 °C. The firing patterns of up to four simultaneously extracellularly recorded STN neurones were analysed using burst and oscillation detection programs (Kaneoke & Vitek, 1996), and correlated activity between pairs of neurones also assessed. Data are shown as means ± S.E.M. Statistical comparisons used Student’s paired t tests, or one-way ANOVA followed by Dunnet’s test, with P < 0.01 considered significant.

In control conditions 345/354 STN neurones fired tonically, with an oscillation at 8.3 ± 0.24 Hz. There was no significant cross-correlated activity in 299/300 pairs of neurones (P > 0.01). The excitation caused by 30 mM muscarine reversibly induced burst firing in 1/19 cells, but no correlation was seen in any of 17 neuronal pairs. Similarly, the excitation by 30 mM (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD) reversibly induced bursting in 2/24 cells, but activity in 26 neuronal pairs remained uncorrelated. 6-Cyano-7-nitroquinoxaline-2, 3-dione (CNQX; 10 mM) and DL-2-amino-5-phosphonovaleric acid (APV; 100 mM) did not change firing rate or pattern (n = 22), providing no evidence for a role of glutamatergic collaterals within the STN under these conditions.

Tetraethylammonium (TEA; 10 mM) caused bursting in 77/105 neurones, with an oscillation at 0.79 ± 0.1 Hz and 14.4 ± 2.0 spikes at mean interval of 52.4 ± 8.0 ms per burst. These parameters were unchanged by CNQX and APV (n = 13). Muscarine (30 mM) caused a reversible increase in oscillation frequency in 12/15 neurones in TEA from 0.74 ± 0.15 to 1.10 ± 0.16 Hz (without change in spikes/burst or interval). Bursting was unchanged by 30 mM ACPD in 11/12 neurones. Correlated activity was seen in 5/54 neuronal pairs in TEA alone, 2/11 pairs in TEA and muscarine, and 1/12 pairs in TEA and ACPD. Of all correlated pairs, only one (in TEA alone) showed significant correlation over a lag of < 100 ms, rendering a contribution from a local synaptic network unlikely.

The bursting seen here is generally unaccompanied by the synchronous activity that appears (pathologically) in vivo, and probably reflects intrinsic STN neuronal properties, rather than network activity. The circuitry needed to produce synchrony in the STN is probably not intrinsic to the STN itself, but probably requires connections with other BG nuclei, and/or the cortex, which are absent in this preparation.

This work was supported by the Parkinson’s Disease Society.

All procedures accord with current UK legislation.