Modifications in glutamatergic transmission after dopamine depletion of the nucleus accumbens. A combined in vivo/in vitro electrophysiological study in the rat.
The interaction between the glutamatergic and dopaminergic input in the nucleus accumbens was examined by studying the effects of dopamine depletion of the nucleus accumbens on the local field potentials, and the L-glutamate elicited responses of the nucleus accumbens in anaesthetized rats in vivo. A characteristic field potential in the nucleus accumbens is evoked by electrical stimulation of the fornix/fimbria fibres, with a monosynaptic positive peak at 10 ms (P10). Rats were unilaterally injected with 6-hydroxydopamine in the nucleus accumbens. The contralateral accumbens was sham lesioned. The rats were divided into short-term and long-term survival groups of one to two weeks and 24 weeks, respectively. In the short-term group, a striking increase (up to three times) of the amplitude of the P10 components, at the site of the lesion, compared with the sham lesioned contralateral accumbens and untreated rats, was found. The long-term group could still display a slight increase although on average this was not significantly different from controls. In the short-term group, at the centre of the lesion, the paired-pulse facilitation ratio was significantly smaller than at the more ventral, less denervated, border of the accumbens. These differences were no longer visible in the long-term group. Single-unit activity of the accumbens, elicited by the iontophoretical application of L-glutamate showed, in controls, a maximal firing frequency ranging from 5 to 40 Hz (mean 25 Hz), whereas in the short-term group more than 50% of the accumbens neurons fired with higher frequencies, reaching up to 90 Hz (mean 55 Hz). In the long-term group the firing frequency varied from 5 to 60 Hz (mean 41 Hz). No changes in threshold ejection glutamate current were found for both lesioned groups. In control rats the L-glutamate elicited responses of six cells tested could be suppressed by dopamine whereas in lesioned rats three of the six cells tested were unresponsive to dopamine. Intracellular recordings of accumbens cells in slices in 6-hydroxydopamine and sham lesioned rats, showed no significant changes in the intrinsic membrane properties, e.g. resting membrane potential, input resistance, spike threshold, action potential amplitude or duration. We conclude that dopamine denervation leads to an increase of excitability of the principal accumbens neurons. This is reflected by the increase of the firing frequency of these cells and of the amplitude of the evoked field potentials. The former is more likely of postsynaptic origin whereas the latter may also have a presynaptic contribution. These effects cannot be attributed to changes in intrinsic membrane properties of the cells.
Mulder
A B
AB
Graduate School of Neurosciences, Faculty of Biology, University of Amsterdam, The Netherlands.
Manshanden
I
I
Vos
P E
PE
Wolterink
G
G
van Ree
J M
JM
Lopes da Silva
F H
FH
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000172:deficiency*; D004594:Electrophysiology; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology*; D007478:Iontophoresis; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
D018663:Adrenergic Agents; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D016627:Oxidopamine; D004298:Dopamine