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Dopamine cells are neurones too!
LETTERS
Neurosim In response to the letter from Michael Vanier1 commenting upon the recent TINS review of Neurosim2, may I point out that Neurosim and GENESIS are completely different types of programs with completely different aims. I make no criticism of the GENESIS program (of which Vanier is co-developer) or the other researchorientated simulations that he mentions, but they do a different job from Neurosim. The aim of Neurosim is to provide a tool to help teach neurophysiology at the undergraduate and early graduate level3, although it might also provide entertainment and insight for faculty themselves2. A major part of the programming effort has gone into the design and implementation of pedagogic-related issues. Its use requires no programming skills, and most ordinary undergraduate students learn to operate it competently within a very short time (10–15 minutes). It runs on an entry-level PC under Windows 3.1 or Win 95. GENESIS, on the other hand, is aimed at research users
Dopamine cells are neurones too! The article by Calabresi1 draws attention to the involvement of two transmitter systems (glutamate and dopamine) that modulate synaptic transmission in the neostriatum. The idea of heterosynaptic plasticity, in which dopamine acts to modulate neurotransmission at glutamatecontaining synapses, is especially relevant in the context of the recent paper by Schultz and Mirenowicz2 showing that midbrain dopamine neurones are activated by positive reinforcement. However, there is some prejudice in the way the two transmitter systems are treated differently in the Calabresi article: glutamate is considered in relation to phasic stimulus-elicited release from corticostriatal terminals, whereas dopamine is considered only in relation to tonic ‘bath’ application. This attitude is encouraged by the fact that L-DOPA does cause a reduction in the symptoms of dopamine depletion in Parkinson’s disease. Nonetheless, a contemporary understanding of the dopamine system emphasizes that it has both tonic and phasic aspects (related to different firing modes of the dopamine neurone)3. Application of dopamine in a pulsatile manner, intended to mimic the release of dopamine produced by phasic activity, results in effects that seem to be the
and the ‘future computational neurobiologists’4. It is mainly used to develop complex models of real neural systems using detailed anatomical and physiological information. It runs on a Unix station under X-Windows. The specific teaching role Vanier mentions is in a course5 intended for ‘advanced graduate students, postdoctoral fellows, and faculty members’ and for which ‘familiarity with neurophysiology, basic mathematics (that is, calculus, linear algebra and differential equations) and computer programming is highly desirable’. In other words, Neurosim and GENESIS are targeted at, and appropriate for, completely different audiences. Neurosim has been extensively tested on real students and real tutors, and its interface design6 and pedagogic effectiveness have been independently reviewed and evaluated in the classroom7. It won the BT Technology for Learning in Science Prize in the national 1995 Partnership Awards in the UK. W.J. Heitler
Sciences, University of St Andrews, St Andrews, Fife, UK KY16 8LB. References 1 Vanier, M.C. (1996) Trends Neurosci. 19, 190 2 Revest, P. (1995) Trends Neurosci. 18, 556 3 http://www.liv.ac.uk/ctibiol/lsec/ february96/Neurosim.html 4 Bower, J.M. and Beeman, D. (1995) The Book of GENESIS, Springer/TELOS 5 Methods in Computational Neuroscience: http://www.mbl.ed/html/GUIDE/ course.11.html 6 http://www-hpcc.astro.washington.edu/ scied/biofaq.html 7 http://www.liv.ac.uk/ctibiol/lsec/ february96/Real.and.Virtual.Experiments. html
CORRIGENDUM In the Letter to the Editor by M.C. Vanier in the May issue of TINS (Vol. 19, p. 190), reference 1 was incorrect. The correct reference is shown below. We apologize to the authors and to the readers for this error.
Gatty Marine Laboratory, School of Biological and Medical
1 Revest, P. (1995) Trends Neurosci. 18, 556
opposite of those seen following bath application. We have recently shown that pulsatile application of dopamine at the time of the tetanizing cortical stimulation produces long-term potentiation (LTP), instead of long-term depression (LTD)4. Our experiments approximate the situation that would occur in a postively reinforced trial. We would like to suggest LTD as a possible mechanism for extinction of unrewarded behaviour (corresponding to tonic firing of the dopamine neurones), and LTP as a mechanism for reinforcement of rewarded behaviour (corresponding to phasic burst firing of the dopamine neurones). Such a phasic action of dopamine might, or might not, be independent of the mechanisms that Calabresi invokes for the explanation of disease states. Although dopamine neurones do not seem to respond during aversive conditioning2, they are silenced by the non-delivery of expected rewards5. That is, a reduction in tonic dopamine release might signal the failure of a previously learned prediction of reward – an error. Thus the removal of tonic dopamine that occurs in Parkinson’s
disease would be equivalent to a permanent error signal in the striatum which might extinguish all movement. This could provide an alternative model of akinesia, but our point here is simply to draw attention to the absence from the Calabresi review of reference to the phasic actions of dopamine. We consider it too soon to relegate dopamine to the neurohumoral role suggested in the review.
Reply We appreciate the comments by Arbuthnott and Wickens on our recent article1 on the role of dopamine in the modulation of corticostriatal transmission. We disagree with the criticisms of these authors, which argue that in our review
Copyright © 1996, Elsevier Science Ltd. All rights reserved. 0166 - 2236/96/$15.00
TO THE EDITOR
G.W. Arbuthnott J.R. Wickens Preclinical Vet Sciences, University of Edinburgh, R(D) SVS, Summerhall, Edinburgh, UK EH9 1QH. References 1 Calabresi, P. et al. (1996) Trends Neurosci. 19, 19–24 2 Schultz, W. and Mirenowicz, J. (1996) Nature 379, 449–451 3 Grace, A.A. and Bunney, B.S. (1984) J. Neurosci. 4, 2866–2876 4 Wickens, J.R., Begg, A.J. and Arbuthnott, G.W. (1996) Neuroscience 70, 1–6 5 Mirenowicz, J. and Schultz, W. (1994) J. Neurophysiol. 72, 1024–1027
we ‘relegate dopamine to a neurohumoral role’. They claim that our idea about the physiological effects of striatal dopamine was obtained ‘in relation to tonic bath application’. We believe that endogenous (and not ‘bath-applied’) dopamine is required for the generation of synaptic plasticity. This idea is supported by several TINS Vol. 19, No. 7, 1996
279
Neurosim In response to the letter from Michael Vanier1 commenting upon the recent TINS review of Neurosim2, may I point out that Neurosim and GENESIS are completely different types of programs with completely different aims. I make no criticism of the GENESIS program (of which Vanier is co-developer) or the other researchorientated simulations that he mentions, but they do a different job from Neurosim. The aim of Neurosim is to provide a tool to help teach neurophysiology at the undergraduate and early graduate level3, although it might also provide entertainment and insight for faculty themselves2. A major part of the programming effort has gone into the design and implementation of pedagogic-related issues. Its use requires no programming skills, and most ordinary undergraduate students learn to operate it competently within a very short time (10–15 minutes). It runs on an entry-level PC under Windows 3.1 or Win 95. GENESIS, on the other hand, is aimed at research users
Dopamine cells are neurones too! The article by Calabresi1 draws attention to the involvement of two transmitter systems (glutamate and dopamine) that modulate synaptic transmission in the neostriatum. The idea of heterosynaptic plasticity, in which dopamine acts to modulate neurotransmission at glutamatecontaining synapses, is especially relevant in the context of the recent paper by Schultz and Mirenowicz2 showing that midbrain dopamine neurones are activated by positive reinforcement. However, there is some prejudice in the way the two transmitter systems are treated differently in the Calabresi article: glutamate is considered in relation to phasic stimulus-elicited release from corticostriatal terminals, whereas dopamine is considered only in relation to tonic ‘bath’ application. This attitude is encouraged by the fact that L-DOPA does cause a reduction in the symptoms of dopamine depletion in Parkinson’s disease. Nonetheless, a contemporary understanding of the dopamine system emphasizes that it has both tonic and phasic aspects (related to different firing modes of the dopamine neurone)3. Application of dopamine in a pulsatile manner, intended to mimic the release of dopamine produced by phasic activity, results in effects that seem to be the
and the ‘future computational neurobiologists’4. It is mainly used to develop complex models of real neural systems using detailed anatomical and physiological information. It runs on a Unix station under X-Windows. The specific teaching role Vanier mentions is in a course5 intended for ‘advanced graduate students, postdoctoral fellows, and faculty members’ and for which ‘familiarity with neurophysiology, basic mathematics (that is, calculus, linear algebra and differential equations) and computer programming is highly desirable’. In other words, Neurosim and GENESIS are targeted at, and appropriate for, completely different audiences. Neurosim has been extensively tested on real students and real tutors, and its interface design6 and pedagogic effectiveness have been independently reviewed and evaluated in the classroom7. It won the BT Technology for Learning in Science Prize in the national 1995 Partnership Awards in the UK. W.J. Heitler
Sciences, University of St Andrews, St Andrews, Fife, UK KY16 8LB. References 1 Vanier, M.C. (1996) Trends Neurosci. 19, 190 2 Revest, P. (1995) Trends Neurosci. 18, 556 3 http://www.liv.ac.uk/ctibiol/lsec/ february96/Neurosim.html 4 Bower, J.M. and Beeman, D. (1995) The Book of GENESIS, Springer/TELOS 5 Methods in Computational Neuroscience: http://www.mbl.ed/html/GUIDE/ course.11.html 6 http://www-hpcc.astro.washington.edu/ scied/biofaq.html 7 http://www.liv.ac.uk/ctibiol/lsec/ february96/Real.and.Virtual.Experiments. html
CORRIGENDUM In the Letter to the Editor by M.C. Vanier in the May issue of TINS (Vol. 19, p. 190), reference 1 was incorrect. The correct reference is shown below. We apologize to the authors and to the readers for this error.
Gatty Marine Laboratory, School of Biological and Medical
1 Revest, P. (1995) Trends Neurosci. 18, 556
opposite of those seen following bath application. We have recently shown that pulsatile application of dopamine at the time of the tetanizing cortical stimulation produces long-term potentiation (LTP), instead of long-term depression (LTD)4. Our experiments approximate the situation that would occur in a postively reinforced trial. We would like to suggest LTD as a possible mechanism for extinction of unrewarded behaviour (corresponding to tonic firing of the dopamine neurones), and LTP as a mechanism for reinforcement of rewarded behaviour (corresponding to phasic burst firing of the dopamine neurones). Such a phasic action of dopamine might, or might not, be independent of the mechanisms that Calabresi invokes for the explanation of disease states. Although dopamine neurones do not seem to respond during aversive conditioning2, they are silenced by the non-delivery of expected rewards5. That is, a reduction in tonic dopamine release might signal the failure of a previously learned prediction of reward – an error. Thus the removal of tonic dopamine that occurs in Parkinson’s
disease would be equivalent to a permanent error signal in the striatum which might extinguish all movement. This could provide an alternative model of akinesia, but our point here is simply to draw attention to the absence from the Calabresi review of reference to the phasic actions of dopamine. We consider it too soon to relegate dopamine to the neurohumoral role suggested in the review.
Reply We appreciate the comments by Arbuthnott and Wickens on our recent article1 on the role of dopamine in the modulation of corticostriatal transmission. We disagree with the criticisms of these authors, which argue that in our review
Copyright © 1996, Elsevier Science Ltd. All rights reserved. 0166 - 2236/96/$15.00
TO THE EDITOR
G.W. Arbuthnott J.R. Wickens Preclinical Vet Sciences, University of Edinburgh, R(D) SVS, Summerhall, Edinburgh, UK EH9 1QH. References 1 Calabresi, P. et al. (1996) Trends Neurosci. 19, 19–24 2 Schultz, W. and Mirenowicz, J. (1996) Nature 379, 449–451 3 Grace, A.A. and Bunney, B.S. (1984) J. Neurosci. 4, 2866–2876 4 Wickens, J.R., Begg, A.J. and Arbuthnott, G.W. (1996) Neuroscience 70, 1–6 5 Mirenowicz, J. and Schultz, W. (1994) J. Neurophysiol. 72, 1024–1027
we ‘relegate dopamine to a neurohumoral role’. They claim that our idea about the physiological effects of striatal dopamine was obtained ‘in relation to tonic bath application’. We believe that endogenous (and not ‘bath-applied’) dopamine is required for the generation of synaptic plasticity. This idea is supported by several TINS Vol. 19, No. 7, 1996
279