SEARCH

SEARCH BY CITATION

Non-technical summary  The loss of dopamine-containing neurons within the substantia nigra has been implicated in Parkinson's disease. Thus, the question why these neurons are particularly vulnerable to excitotoxicity has received considerable attention. Under physiological conditions dopamine neurons can generate a burst of activity that seems to require NMDA receptors and that is activated by high frequency glutamatergic inputs. Here, we show in a brain slice preparation of mice that NMDA receptor activation further excites the neurons by recruiting a calcium-activated non-selective cation current (ICAN) and we hypothesize that ICAN is specifically mediated by a transient receptor potential (TRP) channel. We used RT-PCR methods to confirm expression of TRPM2 and TRPM4 mRNA in substantia nigra pars compacta. We propose that ICAN is selectively activated during burst firing to boost NMDA currents and allow plateau potentials. This boost mechanism may render DA cells vulnerable to excitotoxicity.

Abstract  Nigral dopamine neurons are transiently activated by high frequency glutamatergic inputs relaying reward-predicting sensory information. The tonic firing pattern of dopamine cells responds to these inputs with a transient burst of spikes that requires NMDA receptors. Here, we show that NMDA receptor activation further excites the cell by recruiting a calcium-activated non-selective cation current (ICAN) capable of generating a plateau potential. Burst firing in vitro is eliminated after blockade of ICAN with flufenamic acid, 9-phenanthrol, or intracellular BAPTA. ICAN is likely to be mediated by a transient receptor potential (TRP) channel, and RT-PCR was used to confirm expression of TRPM2 and TRPM4 mRNA in substantia nigra pars compacta. We propose that ICAN is selectively activated during burst firing to boost NMDA currents and allow plateau potentials. This boost mechanism may render DA cells vulnerable to excitotoxicity.