NEWS AND VIEWS reduce fear-related responses to a conditioned awake or asleep)?The answers to theoretically 5.Hauner,K.K.,Howard,J.D.,Zelano,C.Gottfried,J.A. stimulus that does not actually have to be pre- intriguing questions such as these are not yet Nat.Neurosci.16,1553-1555(2013). 6.Arzi,A.et al.Nat.Neurosci.15,1460-1465 sented to the patient.Testing the Hauner et al.5 known.Whether or not such effects can be (2012). context re-exposure procedure in humans who achieved during the awake state,the study by 7. Marlin,N.A.Leam.Motiv.13,526-541 (1982). 8.Stout,S.C.Miller,R.Behav.Processes 66,7-16 are in a state of quiet wake would seem to be a Hauner et al.s adds a new dimension to our (2004). logical next step to further evaluate the poten- understanding of the learning-or,to be more 9.Ben-Yakov,A.,Eshel,N.Dudai,Y.J.Exp.Psychol. tial clinical relevance of this procedure.These precise,unlearning-that can be achieved by Gen. published online,doi:10.1037/a0033558 (1July2013). results may show that the extinction-related the sleeping brain. 10.Buzsaki.G.Neurosci 31.551-570(1989). effects of procedures used during slow-wave 11.Karlsson,M.P.Frank,L.M.Nat.Neurosci.12, COMPETING FINANCIAL INTERESTS 913-918(2009). sleep are also true of procedures used during The author declares no competing financial interests. 12.Wixted,J.T.Annu.Rev.Psychol.55,235-269 quiet wake.Such a finding would have both (2004). clinical and theoretical relevance.Which 1.Rasch,B.,Buchel,C..Gais,S.Born,J.Science 315 13.Mednick,S.C.,Cai,D.J.,Shuman,T. 1426-1429(2007). Anagnostaras,S.Wixted,J.T.Trends Neurosci. consolidation-related effects are specific to sleep 2.Diekelmann,S.Born,J.Nat.Rev.Neurosci.11, 34.504-5142011). and which are instead specific to conditions in 114-126(2010). 14.Dewar,M.,Alber,J.,Butler,C.,Cowan,N.&Della Sala,S. 3.Maren,S.Neuron70.830-845(2011). Psychol..Sc1.23.955-960(2012). which the formation ofextraneous memories is 4. Lattal,K.M.Wood,M.A.Nat.Neurosci.16. 15.Tambini,A..Ketz,N.&Davachi,L.Neuron 65, reduced to a minimum(whether the subject is 124-12920131 280-290(2010). Best-laid schemes for interneuron origin of mice and men Zoltan Molnar Simon J B Butt 复 Two studies emphasize similarities in the developmental origin of cortical interneurons across mammals. They suggest that most interneurons in humans and macaques have a subcortical origin. The complex function of the mammalian tangential migration.Furthermore it would of neuronal precursors from the medial,lateral neocortical circuitry depends on the balance appear that interneuron precursors do not and caudal ganglionic eminences with genetic between diverse subpopulations of excitatory proliferate further after reaching the cor- profiles similar to those that we would expect in pyramidal projection neurons and inhibitory tical plate.Estimates are that,in the dor- the mouse. GABAergic interneurons.Understanding how sal telencephalon of rodents,less than 5% Although the basic organization of cortical these cell types sculpt behavior has become of GABAergic interneurons are generated microcircuits is conserved across mammals, increasingly reliant on genetic technologies locally.It has become evident that there are cell numbers and gene expression patterns to a priori identify cell types with distinct several distinct sources in the ventral tel- in adult and developing human and monkey morphological and electrophysiological encephalon for interneurons.Initial in vitro cortex are very different from those in the properties-aspects that in murine models and in vivo cell tracing and cell transplanta- mouse.Since the identification of distinct can be largely predicted by embryonic ori- tion experiments in rodents have suggested morphological subtypes of interneuron by gin.In primates,including humans,evidence that the medial ganglionic eminence (MGE) Ramon y Cajal,it has often been argued that has suggested there is a substantial difference is the primary source of cortical interneurons. the variety and diversity of these cells increases from rodents in the location from which cor- However,it was clear from these studies that in higher mammals3.These differences can tical interneurons originate.In this issue of other sources provide cells,and subsequent also be extended to the embryonic origin of Nature Neuroscience,Hansen et al.and Ma genetic fate mapping experiments identified interneurons,with monkey and human tel- et al.2 extensively characterize developmental the caudal ganglionic eminence (CGE)as a encephalic germinal zones possessing more gene expression patterns in the ganglionic major contributor to interneuron diversity. elaborate cytoarchitectonic distinctions and eminences.These patterns indicate that the How such complex processes could be scaled some striking differences in embryonic and vast majority of interneurons in human and up in the developing brain of primates has adult gene expression patterns4.5. macaque monkey have a subcortical origin. sparked debate,not least becauseofevidencethat The first indication that the dorsal VZ or It is generally accepted that most some,if not the majority,of cortical interneurons subventricular zone (SVZ)might produce GABAergic interneurons in the mouse are may originate from the dorsal,pallial ventricular interneuron subtypes came from a combination generated in ventral embryonic forebrain zone (VZ).Hansen et al.and Ma et al.2 revisited of immunohistochemistry and retrovirallabel- and reach the cortex-the site of pyramidal this question and analyzed the organization and ing of human fetal organotypic slice prepara- projection neuron neurogenesis-through expression pattern of the human and monkey tions6.As many as 65%of GABAergic neurons fetal ganglionic eminences and their contribu- in some human neocortical areas expressed Zoltan Molnar and Simon J.B.Butt are in the tions to the origin of cortical interneurons.By the DLX1,DLX2 and MASHI (also known as Department of Physiology,Anatomy and Genetics, doing so,they draw parallels between the ana- ASCLl)transcription factors(associated with University of Oxford,Oxford,UK. tomical and genetic organization of the ganglionic interneuron development in rodents)and origi- e-mail:simon.butt@dpag.ox.ac.uk or eminences in the mouse and the human.These nated from MASHI-expressing progenitors of zoltan.molnar@dpag.ox.ac.uk studies provide evidence for the production the VZ-SVZ of the dorsal forebrain.This view 1512 VOLUME 16 NUMBER 11I NOVEMBER 2013 NATURE NEUROSCIENCE1512 volume 16 | number 11 | NOVEMber 2013 nature neuroscience news and views 5. Hauner, K.K., Howard, J.D., Zelano, C. & Gottfried, J.A. Nat. Neurosci. 16, 1553–1555 (2013). 6. Arzi, A. et al. Nat. Neurosci. 15, 1460–1465 (2012). 7. Marlin, N.A. Learn. Motiv. 13, 526–541 (1982). 8. Stout, S.C. & Miller, R. Behav. Processes 66, 7–16 (2004). 9. Ben-Yakov, A., Eshel, N. & Dudai, Y. J. Exp. Psychol. Gen. published online, doi:10.1037/a0033558 (1 July 2013). 10. Buzsáki, G. Neurosci 31, 551–570 (1989). 11. Karlsson, M.P. & Frank, L.M. Nat. Neurosci. 12, 913–918 (2009). 12. Wixted, J.T. Annu. Rev. Psychol. 55, 235–269 (2004). 13. Mednick, S.C., Cai, D.J., Shuman, T., Anagnostaras, S. & Wixted, J.T. Trends Neurosci. 34, 504–514 (2011). 14. Dewar, M., Alber, J., Butler, C., Cowan, N. & Della Sala, S. Psychol. Sci. 23, 955–960 (2012). 15. Tambini, A., Ketz, N. & Davachi, L. Neuron 65, 280–290 (2010). awake or asleep)? The answers to theoretically intriguing questions such as these are not yet known. Whether or not such effects can be achieved during the awake state, the study by Hauner et al.5 adds a new dimension to our understanding of the learning—or, to be more precise, unlearning—that can be achieved by the sleeping brain. COMPETING FINANCIAL INTERESTS The author declares no competing financial interests. 1. Rasch, B., Büchel, C., Gais, S. & Born, J. Science 315, 1426–1429 (2007). 2. Diekelmann, S. & Born, J. Nat. Rev. Neurosci. 11, 114–126 (2010). 3. Maren, S. Neuron 70, 830–845 (2011). 4. Lattal, K.M. & Wood, M.A. Nat. Neurosci. 16, 124–129 (2013). reduce fear-related responses to a conditioned stimulus that does not actually have to be pre￾sented to the patient. Testing the Hauner et al.5 context re-exposure procedure in humans who are in a state of quiet wake would seem to be a logical next step to further evaluate the poten￾tial clinical relevance of this procedure. These results may show that the extinction-related effects of procedures used during slow-wave sleep are also true of procedures used during quiet wake. Such a finding would have both clinical and theoretical relevance. Which consolidation-related effects are specific to sleep and which are instead specific to conditions in which the formation of extraneous memories is reduced to a minimum (whether the subject is Best-laid schemes for interneuron origin of mice and men Zoltán Molnár & Simon J B Butt Two studies emphasize similarities in the developmental origin of cortical interneurons across mammals. They suggest that most interneurons in humans and macaques have a subcortical origin. Zoltán Molnár and Simon J.B. Butt are in the Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. e-mail: simon.butt@dpag.ox.ac.uk or zoltan.molnar@dpag.ox.ac.uk of neuronal precursors from the medial, lateral and caudal ganglionic eminences with genetic profiles similar to those that we would expect in the mouse. Although the basic organization of cortical microcircuits is conserved across mammals, cell numbers and gene expression patterns in adult and developing human and monkey cortex are very different from those in the mouse. Since the identification of distinct morphological subtypes of interneuron by Ramón y Cajal, it has often been argued that the variety and diversity of these cells increases in higher mammals3. These differences can also be extended to the embryonic origin of interneurons, with monkey and human tel￾encephalic germinal zones possessing more elaborate cytoarchitectonic distinctions and some striking differences in embryonic and adult gene expression patterns4,5. The first indication that the dorsal VZ or subventricular zone (SVZ) might produce interneuron subtypes came from a combination of immunohistochemistry and retroviral label￾ing of human fetal organotypic slice prepara￾tions6. As many as 65% of GABAergic neurons in some human neocortical areas expressed the Dlx1, Dlx2 and Mash1 (also known as ASCL1) transcription factors (associated with interneuron development in rodents) and origi￾nated from Mash1-expressing progenitors of the VZ-SVZ of the dorsal forebrain. This view The complex function of the mammalian neocortical circuitry depends on the balance between diverse subpopulations of excitatory pyramidal projection neurons and inhibitory GABAergic interneurons. Understanding how these cell types sculpt behavior has become increasingly reliant on genetic technologies to a priori identify cell types with distinct morphological and electrophysiological properties—aspects that in murine models can be largely predicted by embryonic ori￾gin. In primates, including humans, evidence has suggested there is a substantial difference from rodents in the location from which cor￾tical interneurons originate. In this issue of Nature Neuroscience, Hansen et al.1 and Ma et al.2 extensively characterize developmental gene expression patterns in the ganglionic eminences. These patterns indicate that the vast majority of interneurons in human and macaque monkey have a subcortical origin. It is generally accepted that most GABAergic interneurons in the mouse are generated in ventral embryonic forebrain and reach the cortex—the site of pyramidal projection neuron neurogenesis—through tangential migration. Furthermore it would appear that interneuron precursors do not proliferate further after reaching the cor￾tical plate. Estimates are that, in the dor￾sal telencephalon of rodents, less than 5% of GABAergic interneurons are generated locally. It has become evident that there are several distinct sources in the ventral tel￾encephalon for interneurons. Initial in vitro and in vivo cell tracing and cell transplanta￾tion experiments in rodents have suggested that the medial ganglionic eminence (MGE) is the primary source of cortical interneurons. However, it was clear from these studies that other sources provide cells, and subsequent genetic fate mapping experiments identified the caudal ganglionic eminence (CGE) as a major contributor to interneuron diversity. How such complex processes could be scaled up in the developing brain of primates has sparked debate, not least because of evidence that some, if not the majority, of cortical interneurons may originate from the dorsal, pallial ventricular zone (VZ). Hansen et al.1 and Ma et al.2 revisited this question and analyzed the organization and expression pattern of the human and monkey fetal ganglionic eminences and their contribu￾tions to the origin of cortical interneurons. By doing so, they draw parallels between the ana￾tomical and genetic organization of the ganglionic eminences in the mouse and the human. These studies provide evidence for the production npg © 2013 Nature America, Inc. All rights reserved