Unilateral dopamine denervation blocks corticostriatal LTP
Authors: B Picconi
G Bernardi
P Giacomini
P Calabresi
P Gubellini
D Centonze
Journal: Journal of Neurophysiology (1999)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: nigrostriatal dopaminergic projection; motor information; Parkinson's disease; excitatory transmission; electrophysiological recordings
Affiliations: Dipartimento di Neuroscienze, Clinica Neurologica, Università di "Tor Vergata", Italy.

Abstract:  The nigrostriatal dopaminergic projection is crucial for the striatal processing of motor information received from the cortex. Lesion of this pathway in rats causes locomotor alterations that resemble some of the symptoms of Parkinson's disease and significantly alters the excitatory transmission in the striatum. We performed in vitro electrophysiological recordings to study the effects of unilateral striatal dopamine (DA) denervation obtained by omolateral nigral injection of 6-hydroxydopamine (6-OHDA) in the formation of corticostriatal long-term potentiation (LTP). Unilateral nigral lesion did not affect the intrinsic membrane properties of striatal spiny neurons. In fact, these cells showed similar pattern of firing discharge and current-voltage relationship in denervated striata and in naive controlateral striata. Moreover, excitatory postsynaptic potentials (EPSPs) evoked by stimulating corticostriatal fibers and recorded from DA-denervated slices showed a pharmacology similar to that observed in slices obtained from controlateral intact striata. Conversely, in magnesium-free medium, high-frequency stimulation (HFS) of corticostriatal fibers produced LTP in slices from nondenervated striata but not in slices from 6-OHDA-denervated rats. After denervation, in fact, no significant changes in the amplitude of extra- and intracellular synaptic potentials were recorded after the conditioning HFS. The absence of corticostriatal LTP in DA-denervated striata might represent the cellular substrate for some of the movement disorders observed in Parkinson's disease. 

Retracted: No

PubPeer comments:
 Figure 1B, purportedly measured from cells in the rat shows identical data to a figure from another study (same authors), purportedly from cell in the mouse. Here is Figure 1B from this study (trace in red was overlaid to compare it to the next study) ![file] Here is Figure 3B from[ the other study ] published in Journal of Neuroscience. The red curves and data points are the same as in the previous study. Same exact values. ![file] A possible conclusion is that cells in naive rats are identical to cells in wild type mice, and cells in DA-denervated rats are identical to cells in knockout mice. This seems unlikely. , 
 These issues refer to papers written more than 20 years ago. For this reason, we do not have anymore access to the original data. We remember that similar questions were raised by the Editors of the Journals (J Neurophysiology and J Neuroscience) according to the requests of independent readers. Following the analysis of the traces we admitted that, in some cases, mistakes were done reporting the same curves in different experimental conditions, and for one case the values of two graphs - which were very similar but not the same - were sent to the Editor. However, considering that those data were related to negative findings, these issues did not alter the core messages of the studies that were based on several other positive findings. The Editors accepted this explanation. During the following 20 years we and other groups confirmed and replicated these negative findings with several different sets of experiments. From a more technical point of view, it should be noted that the currents for building these i-V curves were not computer recorded, but they were printed on graph paper rolls (similar to those still used for ECGs) and then measured by hand. Thus, very close current values were measured as equal. This said, we believe that, at that time, we choose to show i-V relationships that were as close as possible, hence the fact that graphs appear identical when superposed: their values were probably very close - if not identical - for the above reasons. Furthermore, the Y scale (1600 pA) is too large to allow discerning differences of 10-20 pA or less. Again, we cannot exclude that mistakes were done and we used the same data for different graphs, and in this case we apologize, but these 20-year old data are not anymore available to check. Finally, these possible mistakes do not impact the overall message of the paper: the data concerning the main points of the paper still stands. ,