Dopamine neurons of the substantia nigra, notorious for degenerating in Parkinson’s disease, are constantly on the hot bench of basic studies. Aside from their marked death in the aforementioned disease, they are implicated in reward and motivation. As with all diseases, and the main focus of neuroscience – understanding the underlying mechanism of function of the nervous system, the challenge is to get at the underpinnings in the healthy system which may offer clues as to what might be occurring in the diseased state. Along those lines, understanding the developing brain and how the excitability of single neurons change over time may lead us to pinpoint critical stages for disease intervention. This was the subject of the following poster I enjoyed today –
“Electrophysiological and molecular development of rat substantia nigra compacta dopaminergic neurons” – Author Block: *M. DUFOUR1, A. WOODHOUSE2, J. AMENDOLA3, J.-M. GOAILLARD3; 1INSERM, Marseille, France; 2Univ. of Tasmania, Hobart, Australia; 3INSERM UMR1072, Marseille, France.
In examining the basic electrophysiological properties of the compacta dopamine neurons, they found that the P2 dopamine neurons fired with burst like activity and exhibited a pronounced AHP. This firing mode changed in as little as 3 days, with the firing regularity increasing significantly by P5 and by above P12 or so, the neurons exhibited regular pacemaking activity which is a firing characteristic of these neurons. The coefficient of variation of the interspike interval was also markedly reduced over time as the rats advanced in age.
Along the lines the change in their electrical properties, they also observed an decrease in the input resistance (which was in the thousands of megaOhms at P2!) and the extent of spike adaptation (consistent with a shift in their burst-like pattern of firing to a tonic firing pattern).
The same pattern of change was also observed with the sag amplitude in response to hyperpolarization (indicative of H-current). They saw an increase in sag amplitude as the rats got older.
Finally, taking 8 different electrophysiological membrane properties – interspike interval, input resistance, AHP amplitude amongst others, they performed both an augmentive and PCA clustering analysis to determine the classification that would emerge from all the neurons recorded regardless of age. True to their experimental observations, three classes emerged – P0-P2/3, P5-7 and older which displayed distinct firing patterns.
I appreciated the work they did, especially as there are few papers out there that attempt to chronicle the change in the electrophysiological properties of compacta dopamine neurons. It also raises a valid concern on the age of rodents being routinely used for electrophysiological slice recordings especially when these questions have nothing to do with development. Additionally, the change in distinct electrophysiological hallmark features of the dopamine neurons over time raise the obvious question of the complement of ion channels in these neurons as they age, and their key modulators. Are these same ion channels that develop with time also affected in parkinson’s? What key modulators control the complement of ion channels that shape their changing excitability over time? Could these modulators that affect their development also be used later in life to enhance neighboring compacta neurons and probably enhance neuroprotection to prevent their future neurodegeneration (that is in the event of of early disease onset)?
More to come from @noviceneuroscientist in Sunny San Diego #neuroscience13 #sfn13