Talk:Dopamine modulation
Correction to the following sentence: "Using in vivo recordings from the striatum of awake rats Reynolds et al. (2001) found that stimulation of the substantia nigra induced potentiation of synapses between the cortex and the striatum with the degree of potentiation correlating with the time taken by the rats to learn a lever press behavior."
In the cited paper, it appears that rats weren't awake, but anesthetized while recording from striatum and measuring corticostriatal synaptic efficacy. Although rats performed the lever pressing/intracranial self stimulation task several days prior to anesthetization, alas, no striatal recordings during this period were reported.
Overall, this is a nice (if at least slightly biased) review of this literature. However, there are some glaring inaccuracies that must be addressed:
1. Basic electrophysiology section - There is no evidence that increasing burst firing alone will cause an increase in tonic extracellular DA levels. Causing DA neurons to burst fire naturally by activating glutamate inputs does not increase microdialysis levels of DA, but may transiently increase DA perisynaptically as shown with local voltammetric measures. However, stimulating DA axons in a burst manner will activate ALL axons, thereby increasing both tonic and phasic input, and doing it by simultaneously activating all terminals; a clearly non-physiological process. All data collected from “natural” burst firing shows that it does not affect tonic extracellular DA levels.
I believe this critique is in reference to the following: "Phasic activation of DA neurons increases their firing rates to ~20Hz which also results in significant increases in extracellular DA concentrations." If this is indeed the line in question, please note that no mention was made of tonic levels, only that extracelular levels were increased by phasically activating DA neurons. I believe this is consistent with the statement of the reviewer that natural burst firing may increase DA perisynaptically as measured with voltammetry. However,if burst stimulation can even transiently increase perisynaptic DA levels (e.g. Murase et al. 1993), this will add to the pool of DA levels in the PFC because of the inefficiency of re-uptake. Indeed increasing the frequency of DA transients can produce a gradual increase in extracelular DA (Wightman et al. 2007). Nevertheles to clarify this point, the word "transient" rather than "phasic" might be more appropriate.
Most of the changes made were quite appropriate; however, I believe that the insertion of the term "transient" was not done in the most effective manner; I believe the authors should keep "phasic" in the part of the sentence "Phasic activation of DA neurons..." since that is the term used to denote burst firing by those studying this phenomenon in both rodents and primates. However, the word "transient" SHOULD be included in the second part of the sentence "which also results in significant BUT TRANSIENT increases in extracellular DA concentrations.: This would be acceptable by those that record either using microdialysis or voltammetry, and that believe either that DA is removed primarily by reuptake, as well as by those who believe that diffusion is the primary means if inactivating DA transmission.
2. In vivo physiology – the authors have ignored the only paper to measure how endogenous synaptically released DA will affect striatal neuron firing. West & Grace showed that D2 antagonists administered locally via microdialysis will increase striatal neuron activity, whereas D1 antagonists attenuate excitability.
I think this is a terrific paper and I have heavily cited it in the past. This was an unintentional oversight and it will be added.
3. The Penit-Soria reference has to be taken with caution, since DA at these exceedingly high doses is an effective NE agonist, and the effects they report resemble what others (Woodward) have shown with much lower doses of NE.
I agree with the point of the reviewer. However, given this was a seminal early paper, it would be preferable to keep it in the article.
Yes, this is historic, but it is also misleading and incorrect in its interpretation. You really need to keep from perpetuating a falsehood regardless of the historical nature.
4. In the in vivo section, the authors fail to mention the substantial literature showing D2 attenuation of mPFC input to the striatum (both dorsal and ventral), which has important implications for the function of this system.
This point highlights the initial observation of the reviewer who I believe was implying that the article was biased towards the PFC literature. This was the case, but perhaps revising this section will help alleviate that problem.
