Potentiation of NMDA receptor-mediated transmission in striatal cholinergic interneurons.
Pauses in the tonic firing of striatal cholinergic interneurons (CINs) emerge during reward-related learning in response to conditioning of a neutral cue. We have previously reported that augmenting the postsynaptic response to cortical afferents in CINs is coupled to the emergence of a cell-intrinsic afterhyperpolarization (AHP) underlying pauses in tonic activity. Here we investigated in a bihemispheric rat-brain slice preparation the mechanisms of synaptic plasticity of excitatory afferents to CINs and the association with changes in the AHP. We found that high frequency stimulation (HFS) of commissural corticostriatal afferents from the contralateral hemisphere induced a robust long-term depression (LTD) of postsynaptic potentials (PSP) in CINs. Depression of the PSP of smaller magnitude and duration was observed in response to HFS of the ipsilateral white matter or cerebral cortex. In Mg(2+)-free solution HFS induced NMDA receptor-dependent potentiation of the PSP, evident in both the maximal slope and amplitude of the PSP. The increase in maximal slope corroborates previous findings, and was blocked by antagonism of either D1-like dopamine receptors with SCH23390 or D2-like dopamine receptors with sulpiride during HFS in Mg(2+)-free solution. Potentiation of the slower PSP amplitude component was due to augmentation of the NMDA receptor-mediated potential as this was completely reversed on subsequent application of the NMDA receptor antagonist AP5. HFS similarly potentiated NMDA receptor currents isolated by blockade of AMPA/kainate receptors with CNQX. The plasticity-induced increase in the slow PSP component was directly associated with an increase in the subsequent AHP. Thus plasticity of cortical afferent synapses is ideally suited to influence the cue-induced firing dynamics of CINs, particularly through potentiation of NMDA receptor-mediated synaptic transmission.
Department of Anatomy and the Brain Health Research Centre, University of Otago Dunedin, New Zealand.
Manfred J
MJ
Oswald
Department of Anatomy and the Brain Health Research Centre, University of Otago Dunedin, New Zealand.
Jan M
JM
Schulz
Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany.
Wolfgang
W
Kelsch
Department of Anatomy and the Brain Health Research Centre, University of Otago Dunedin, New Zealand.
Dorothy E
DE
Oorschot
Department of Anatomy and the Brain Health Research Centre, University of Otago Dunedin, New Zealand.
John N J
JN
Reynolds
NMDA; cholinergic interneuron; dopamine; pause response; plasticity; reward