Talk:S1 laminar specialization

Reviewer A

The review by Jochen Staiger on ‘S1 laminar specialisation’ is very detailed and the information provided is sound. After a brief account of the S1 cortical structure, it describes from the point of view of the cortical signal flow the neurons and to some extent also the synaptic connections in the cortical layers. Unfortunately, the description of the cellular components of the different cortical layers is somewhat rudimentary in places. This is in part due to our limited knowledge but the author appears to concentrate on excitatory neurons and devotes only a few sentences to the GABAergic interneurons. Here, the author should provide more information. Furthermore, afferent and efferent projections in different layers are barely mentioned. On the other hand, a some sections of this review appear to belong more to other articles of the ‘Encyclopedia of Touch’ (see below). The author should try to avoid generating to much textual overlap with these articles and concentrate on the structure of S1 cortical layers. Overall, I think the author should try to structure the description of cortical layers somewhat more and give more weight to the description to the different cell types in the cortical layers. A short paragraph on the development of cortical layers would not go amiss. Including subheadings such as ‘thalamocortical projections’, ‘excitatory cell types’, ‘inhibitory cell types’, ‘efferent projections’ may help the reader to organise the information provided.

Comparative aspects of S1 cortical layers While a comparison with other primary sensory cortices and/or the S1 cortex in other mammals is certainly an important aspect, as reviewer B pointed out, the ‘Encyclopedia of Touch’ in Scholarpedia is supposed to contain an article on S1 comparative structure which is likely to deal with this point. I think a brief description is completely sufficient here.

Connectivity As described here for the functional and structural aspects of synaptic connections in different cortical layers are only described briefly. This is fitting as another article in the ‘Encyclopedia of Touch’ on S1 cortical microcircuits is supposed to deal with this point. I suggest to cut this section as short as possible and to expand the section on the excitatory and inhibitory cell types, their morphologies and projections.

Molecular markers of neurons The literature on molecular markers is much richer than suggested here (Ng et al., 2009; for reviews s. Bernard et al. 2009; Brown & Hestrin, 2009). In particular, two recent papers by Brown and Hestrin (2009) and Groh and coworkers (2009) demonstrate how powerful this approach when combined with electrophysiology and structural studies. On the other hand, the quotation of Schubert et al. (2007) seems somewhat out of place here. Furthermore, the is a vast literature on interneuron markers such as parvalbumin, calretinin, calbindin, and somatostatin in particular by Kawaguchi and co-workers. The author mentions very few (when describing layer 4). It would be nice if the author would expand a little bit on this point and add some functional aspects here.

Morphology of neurons The author describes some of the pyramidal neuron morphologies and mentions only few of the interneuron morphologies. It would be extremely helpful and contribute to the readability of the article if he could provide figures/reconstructions (not schematics) of these neurons. In particular figures of the different morphologies of interneurons would assist the understanding of the differential functions.

In text references While the ‘Encyclopedia of Touch’ is certainly far from complete, there are already some extremely readable articles which the authors should use as ‘internal reference’. I suggest to refer to the Deschênes/Urbain Article on ‘Vibrissal afferents from trigeminus to cortices’ and desist from a lengthy discussion of the different thalamocortical pathways.

Figures Figures 3 and 7 should be supplied at least in a schematic form (together with their legends).

Reviewer B

In general, I think the article is well written and thorough. Nonetheless, not being an anatomist myself, I am somewhat concerned that it is a little too specialized and lengthy, and thus will not be accessible as-is to a wide enough readership. I would have made the following suggestions, though, in order to increase readability. Please let me know your opinions about my suggestions, or if you need further clarifications about the various points.

Title I would think that “S1 laminar specialization” should be changed to a more appealing name. How about “ S1 cortical layers”, “S1 cortical lamination” or “S1 laminar organization”?

Introductory passage The introductory passage (“In an earlier review…”) is really an apology for the incomplete knowledge we have about the field. I would move this passage further on, and make the introductory passage more Wikipedia-like, by giving a long-dictionary-definition of S1 cortical lamination and a brief summary of the rest of the text.

Missing discussion of comparative lamination I believe the comparative discussion is lacking, and should be made clearer. Clearly, some rodents contain Barrels while other mammals do not, and this is of course a major species difference that should be emphasized. The existence of barrels also has implications to the connectivity. Moreover, it would be nice to highlight what is special about the lamination of S1 relative to other primary sensory areas (such as V1) or to other non-primary cortical regions.

Missing overview of connectivity between layers Before the section entitled “Layers re-visited” I would add a section giving a brief overview of the major connectivity patterns between the layers, so that a reader who is less interested in the “gory details” could read at least the first part of the article and know the essentials (such as the surprising distinction between layers 5a and 5b, which may be strange to those who are from out of the field).

Missing discussion of barrels/septa It could be nice to discuss more clearly the differences in connectivity between barrels and septa. Although it is shown in figure 5, I think it is lacking in the text. Also, it is not completely clear from the text how the different pathways (lemniscal, paralemniscal, extralemniscal) terminate differentially on the different layers.

Confused description of inputs/outputs to different layers from/to other brain regions I believe it would have been nice if there would have been a more organized discussion in the text of the main inputs and outputs to/from sub-cortical and other brain regions to/from each layer (thus making a summary of figure 4 inside the text too). Also, I believe the discussion of what are the extra-cortical inputs to the different layers was less clear to me (similar to figure 4, but for inputs). I would suggest adding a figure similar to figure 4, but describing the inputs to each layer similar to the way figure 4 is describing the outputs.

Very partial discussion of function I would have added a more thorough discussion of the function of the different layers. It is true that our knowledge about function is very limited; however unlike the impression I got from the text, we do have more knowledge than described about the different function of the different layers, from intracellular recordings, extracellular recordings, and optical imaging. It seems to me extremely important to enhance this aspect.

In order to assist the reader, consider organizing the description of each layer with the following headings: (a) Cell types (b) Inputs (c) outputs (d) function

Missing figures Some figures are mentioned in the text but not provided yet, and should be added.

User 3: Scholarpedia Chapter „S1 cortical laminar organization“ – Response to reviewers by Jochen Staiger

In general I am glad that both reviewers are positive and find the chapter helpful and want to thank them for their many constructive comments! Since the given Title really was very open, it was not very obvious for me with what kind of content it should be filled most suitably. I considered my selection based on my primary competence in cortical circuits, so this became the mostly featured topic. I discovered late that another chapter of this kind was assigned to Dirk Feldmeyer, but as always I consider our work (and opinions) as largely complimentary and not redundant.

The reviews now cause the next obvious conflict, which I had already all the time when preparing the chapter: what concepts to include at what length? On the one hand the reviewers find the chapter long and detailed (which it certainly is), on the other hand, the ask for more information, so much that it easily would fill 4 more chapters (in my opinion). Especially one like “S1 GABAergic interneurons” would be important to be written but not as an inclusion in my chapter. There are two reasons for this: (i) too demanding for me at the moment (there will certainly be updates in the years to come), given all the other request that had to be considered and (ii) I have/there is no clear concept on how to present GABAergic interneurons in terms of layer-specific morphology, connectivity and function. I have stated this now in text. In principle, the same holds true for the additional information requested on development, molecular markers, species comparison, barrel/septum comparison and function.

From the points made, I found most helpful and implemented in the revision: (i) to give a general (Wikipedia-like, hope I got it – I don’t look up too much there) Introduction and not this "excuse paragraph" for still not knowing more (which is unfortunately true), (ii) to prepare a summary diagram for inputs (with which I am not satisfied but could become no better due to the lack of data in the rodent field) as well, (iii) to put the basics of laminar connectivity in front of the main body of the text and (iv) to structure the layer paragraphs more. I would like to ask for help by the organizers of Scholarpedia to cross-link, wherever appropriate, my chapter with the already available one. Furthermore, I would like some more precise suggestions from reviewer 2 on what kind of “known function” of layers to include at the appropriate places. Also more Figures will be included as they become available.

Reviewer B

I am very happy with how the chapter looks now. I think it is a very good review of its subject, and will be a great help to those who are interested in understanding the anatomy of S1 or other primary sensory cortices. There can still be some minor improvements, especially regarding discussion of function, but I do not think this should delay the publication. Additions can be done later. Following the request from Dr. Staiger, I am suggesting to use the following references that have some information about the functions of the different layers: Ito 1985; Ahissar et al 2001; Derdikman et al 2006; Brecht 2007; deKock et al 2009

Small comments on the figures: Figure 3B is unreadable and should be increased in order to make comprehensible. The caption of figure 7 is somewhat cryptic. Also - the letters in the caption (A,B,C) do not correspond to the letters in the figure (A,C,E)

Thank you very much for your the praise and the reference suggestions. I will implement them in the next update.

Review A

Review of the revised Scholarpedia Article by J. Staiger on S1 laminar specialization.

While I think that the present version of the Scholarpedia article on S1 laminar specialization puts to much emphasis on the actual connectivity and less so on the actual neuronal diversity in S1 I consider it much improved. However, a few points remain that should be addressed.

Specific points

To quote Schubert et al. 2007 as the only reference for pyramidal cell diversity is certainly insufficient. There are many more and promising new approaches like those mentioned by Gong et al., 2003 should be quoted as well (perhaps in conjunction with Groh et al., 2010).

Again, it seems a bit short-sighted to refer only to refer only to Schubert et al. 2007 and Lefort et al. 2009 for extensions on the ‘canonical microcircuit’. See e.g. Thomson et al., Svoboda et al., Murray Sherman et al., Feldmeyer et al. Callaway et al. and quote at least some of these references!!

The author subdivides layer II/III into to different laminae. As this cortical layer is often dealt with as one (at least for rodents) the author should introduce a short section why he did this.

For Lamina III the text should be changed to: … due to the presence of an apparently homogeneous population of medium-sized pyramidal cells. It is clear from several publications that pyramidal cells in lamina III (and II) are far from homogeneous, both concerning their input and their projections.

What does ‘subdominant’ mean? ‘Less dominant’ or ‘outweighed by’?

Since the Lefort et al., 2009 do not address cortical interneurons in their study, the reference appears somewhat out of place. Please change to avoid misunderstandings. It is also strange why the author writes that LVI pyramidal cells ‘rarely connected to each other’ while stating that the receive input from LIV and LV input (without using this qualifier). The relative connectivity from LIV, LVa and LVI excitatory neurons is similar (~3%) for all these neurons; it is only higher for LVb pyramidal cells!

In Figure 7 the panels are labelled A, C, E (as in the original Zarrinpar and Callway manuscript) not A, B, C as written in the legend. Please relabel the figure.

Reponse to Review A

Thank you for another round of improvements!

Specific points To quote Schubert et al. 2007 as the only reference for pyramidal cell diversity is certainly insufficient. There are many more and promising new approaches like those mentioned by Gong et al., 2003 should be quoted as well (perhaps in conjunction with Groh et al., 2010).

I am not sure to which part this is referring to. If it is the one describing the laminar compartmentalization in the chapter "What are cortical layers?", we are not claiming that we are the only reference but simply that being one study which showed that a sublamination of LV makes sense in the light of functional differences. Nevertheless, Groh et al. is a very recent publication that makes sense to include here.

Again, it seems a bit short-sighted to refer only to refer only to Schubert et al. 2007 and Lefort et al. 2009 for extensions on the ‘canonical microcircuit’. See e.g. Thomson et al., Svoboda et al., Murray Sherman et al., Feldmeyer et al. Callaway et al. and quote at least some of these references!! On the one hand, this statement is correct since it explicitly is related to "important extensions", without mentioning them, though. On the other hand, there are good and less good reviews. We have referred to most of the good ones just a sentence earlier and even implemented Figures from one (Lübke and Feldmeyer, 2007). Thus, I think it is not short-sighted but appropriate to keep this part as it is.

The author subdivides layer II/III into to different laminae. As this cortical layer is often dealt with as one (at least for rodents) the author should introduce a short section why he did this.

I have now added a short paragraph at the beginning of the "Layer III" chapter to account for this issue. It reads: In certain species and areas (e.g. rodent S1), there are no cytoarchitectural differences between layers II and III. Thus, these two layers are often pooled into a "layer II/III". However, several recent papers have clearly demonstrated that the input-output function (see respective chapters below) of pyramidal cells located close to the pia is different from those located close to the barrels. Therefore, it was chosen to present the two layers here as distinguishable entities, the exact border location of which may become visible with future molecular markers.

For Lamina III the text should be changed to: … due to the presence of an apparently homogeneous population of medium-sized pyramidal cells. It is clear from several publications that pyramidal cells in lamina III (and II) are far from homogeneous, both concerning their input and their projections.

I have preferred to add "morphologically" to "homogeneous population" since the logic of all chapter beginnings is to shortly summarize the appearance in Nissl-stainings.

What does ‘subdominant’ mean? ‘Less dominant’ or ‘outweighed by’?

I have changed that to "outweighed by"

Since the Lefort et al., 2009 do not address cortical interneurons in their study, the reference appears somewhat out of place. Please change to avoid misunderstandings. It is also strange why the author writes that LVI pyramidal cells ‘rarely connected to each other’ while stating that the receive input from LIV and LV input (without using this qualifier). The relative connectivity from LIV, LVa and LVI excitatory neurons is similar (~3%) for all these neurons; it is only higher for LVb pyramidal cells!

It is true that in this paragraph some unintended misunderstandings become possible. Because of that, I have removed the Lefort et al.-reference in the first sentence and added "sparsely" before "afferented" in the second sentence.

In Figure 7 the panels are labelled A, C, E (as in the original Zarrinpar and Callway manuscript) not A, B, C as written in the legend. Please relabel the figure.

This mistake has been corrected.