Layer 6 Notes Summary


See this doc for the previous version of this post which goes with the second post here. Some things in those are wrong.

This version of this post is going to be a bit messy. That’s because I’m not sure whether one of the L6 CT types is an essential component in all regions of all species, with at most limited exceptions. Also, some sources in this batch of notes are interesting but ambiguous, so overall I don’t have much of a framework for interpretation. I decided to just write what I think without getting into my reasoning too much, since that was taking forever to write and organize and it’s tentative anyway until I resolve the ambiguity.

I’ll add in text citations soon. The new sources start on page 20 in my notes.

I still need to check these facts since I wrote this mostly from memory.

The Thalamus

Thalamic cells have tonic mode and burst mode. In tonic mode, the cell fires normally. While inhibited, the cell is in burst mode. It will respond to the start of excitation with a brief additional excitation. This can cause a burst of spikes, but it can also cause a single spike because the size of the brief excitation depends on the duration and magnitude of the preceding inhibition. Bursting is related to oscillations because those provide periods of reduced excitation. Also, single burst mode spikes whether rhythmic or not send a larger signal than tonic mode spikes because of synaptic depression, which also makes later spikes in bursts less impactful.

The TRN receives excitation from and sends inhibition to TC cells. TRN and TC cells both have tonic and burst mode, and TRN cells are connected, so the TRN complicates the thalamus.

In primary thalamus and higher order thalamus respectively, the sensory input and layer 5 drive firing. L6 CT cells send metabotropic long lasting facilitating excitatory signals to all targets including the thalamus, which are fit to switch thalamic cells to tonic mode without exciting them suddenly enough to cause a burst. They target TC cells and TRN cells, so the signals are likely kept in check by inhibitory signals. Modulating TRN cells does not mean L6 CT cells can indirectly cause bursts, as tonic mode TRN cells probably only send metabotropic long lasting inhibitory signals when bursting, and otherwise only send normal inhibitory signals.

Bursting might serve to switch attention. If that is correct, then pathways through the thalamus are non-categorical and direct pathways are categorical because bursting operates in terms of the sensory input rather than the cortical representation, because the sensory input to O1 bypasses the thalamus, because of the parallel CC and CTC pathways up the cortical hierarchy, and because thalamic cells are more bursty in modalities and submodalities which require more changes in the attended sensory patches and less changes in the attended sensory items.

CT Cells and Cortex

The signals sent within the cortex are similar to those sent to the thalamus. The signals to excitatory cells facilitate, but they also target interneurons in each targeted layer. In L6 itself, they mainly target interneurons, although they could target excitatory L6 cells distally since those synapses usually go unnoticed using the methods of these studies. At least in L6, signals to excitatory cells always facilitate, but signals to most inhibitory cells facilitate once and then depress after the second spike. After a while, the signals to L6 excitatory cells might go out of control, so most likely those synapses are distal or interneurons in other layers are involved. CT cells slowly adapt, which is another way to keep facilitating signals in check.

Primary CT Cells

Primary CT cells only project to hierarchically lower thalamic nuclei. For example, in primary cortex, they only project to the primary thalamic nucleus, specifically the one for the same modality.

They receive input from the thalamus, but these synapses are weak and cannot cause firing alone. Instead, they are probably driven by L6 CC cells and possibly L5, both of which send horizontally wide-reaching axons which generally extend to the adjacent cortical column at least. Besides their driving inputs, primary CT cells are columnar. They probably only project to the patch of the thalamus which corresponds to the same column, and their axons and apical tufts are mostly in L4 of the same column. In barrel cortex, they are denser in columns than in the spaces between the columns. However, their columnar nature might not be universal because the second potentially non-universal system has a multi-columnar nature.

There are also dual-projecting CT cells and higher order CT cells in rodents, but these classes might be part of a separate system which might not be part of the fundamental circuitry. Higher order CT cells in these studies are only in the deepest fifth of L6 (L6Bb), which is not studied much so I will mostly ignore them until I find more information, but they are clearly a class in rodents. Dual-projecting CT cells are only in the lowest half of L6 (L6Ba and L6Bb), give or take a few percent, while primary CT cells are only in L6A and L6Ba.

The projections to L4 from primary CT cells probably activate excitatory cells. A study claimed that CT cells inhibit L4 more than they excite it, but based on the figures they accidentally only labelled and activated dual-projecting CT cells and maybe higher order CT cells. Pixel measurements confirm this problem, and the projections to L4 in barrel cortex are probably to the septal parts between columns.

CC Cells

Identifying CC cell types is difficult. They have several unusual morphological classes (like stellate cells and upside-down pyramidal cells, as well as normal pyramidal cells), but I do not have enough information about their inputs and outputs to tell whether they are functionally distinct. Besides CC and CT cells, there are also corticoclaustral cells, but those share many similarities with CC cells and I still need to research them. Lastly, there are Meynert cells in upper layer 6 of V1 which project both corticocortically and to the superior colliculus, but I have not heard of them outside V1.

At least in L6A, CC cells receive stronger inputs from the thalamus than CT cells, at least in terms of average experimentally noticed response. The inputs from primary and higher order thalamus are both larger, but especially the input from higher order thalamus. That does not mean it is a strong source of input, and the higher order nucleus in that study has some unusual or unique traits (the convergence zone discussed regarding the second system) so this input might not be universal.

CC cells respond to synaptic excitation and current injection with a brief depolarization which causes a single spike and then no firing, or briefly elevated firing and then either no firing or normal firing. I do not know whether there is a brief pause in firing immediately after the small number of more rapid spikes, which would make it a burst in a strict sense, but either way, other cells usually require apical input to burst (the exceptions are attributable to methods since they are so variable between studies) so this phasic firing is unusual if it occurs in normal function. Like TC cells, they fire more rapidly when they start firing, and their synapses depress.

Unlike the thalamus, however, CC cells can receive driving signals from hierarchically higher cortical regions. Specifically, M1-projecting CC cells (and perhaps others) receive strong motor copy signals. These M1-projecting cells are throughout L6 but denser in L6A, so they might be a subtype. Regardless, more than half of CC and CT cells respond to head rotation signals sent at least by retrosplenial cortex, so the CC cells probably receive driving motor copy signals. CC and CT cells are inhibited or excited as a result, with amplitude and signs depending on head rotation direction and speed. They could hypothetically only receive signals about rotation from motor cortex, but that seems unlikely because the study about the head rotation signals was on V1, for which other forms of motor copy signals (such as those which activate central pattern generators instead of just causing a joint to rotate) would be hard to find unlike in somatosensory cortex. However, it is also possible that M1 projects mainly to CC cells whereas the retrosplenial cortex projects to both CC and CT cells. Either way, CC and CT cells are both influenced by behavior.

This association with behavior might just reflect the second system since CC cells in upper L6 are denser in the spaces between columns (the septa) and the M1-projecting CC cells are denser in upper L6. That inter-column space is involved in the second system and it might only be activated during behavior by the thalamus, as well as by the direct motor copy signals described here.

CC cells of most or all types have transcolumnar axons in L6 which at least in the same column synapse on CT cells, CC cells, and inhibitory cells. These axons also form synapses in L5. I do not know whether the axons to or from L5 are mostly on interneurons like the axons from L2/3 to L4, although dual-projecting CT cells activate L5 slender tufted cells.

The Second System

The barrel cortex is weird. That is the impetus for this proposal, but it seems likely that the second system is universal to all species but possibly not all regions. The weirdness of the barrel cortex just makes its own second system more obvious.

A whisker only produces sensory inputs by producing forces at its base. That sensation is indirect, but multiple whiskers touch surfaces since there are a couple dozen, so it is like trying to recognize something by touching it with two sticks in the same hand. This analogy is not perfect, though. Whiskers move back and forth rhythmically at neural frequencies, such as five or twenty hertz. They might not be able to recognize objects during whisking because it is so fast, but animals can move their whiskers in other ways besides whisking or keep them still. There is a map of the whisked space in L2/3 during whisking, which makes sense if it recognizes objects because otherwise it would operate in terms of a constantly moving sensor. Another thing you’ll need to know which doesn’t fit anywhere is that each cortical column corresponds to a whisker.

I will draw heavily from the barrel cortex, but the details are not the point. I have no idea how this system works, just that it exists. Details are only evidence and part of the thinking process. Since the barrel cortex is weird, it may need some specializations to implement this system. Those specializations are valid evidence for this universal system, but I need to research this system elsewhere.

More relevant to a review of L6, the second system is a huge problem for getting the facts right. I was editing this post to add information from a batch of notes, but I ran into a problem. As a result, I am not sure whether dual-projecting CT cells are universal, and I cannot research things very well until I figure that out. I’ll have to research rodents and primates and not just primary regions until I run into information which solves this problem.

Here is the background. Dual-projecting CT cells are multi-columnar in nature, unlike primary CT cells. In rodent barrel cortex and visual cortex, they project to an elongated area of the primary thalamus, and they also project to L5a in the same and adjacent columns. So far, these aspects of dual-projecting CT cells seem universal in primary regions of rodents, although maybe not primates.

But barrel cortex is weird. It has septa, meaning space between columns (technically just in layer 4 but not here), which has different connections. Dual-projecting CT cells appear to project to septal L4 in barrel cortex, but any V1 equivalent of septa must be sparse or not targeted by dual-projecting CT cells because they do not project into layer 4. Also, septal L4 receives input from the higher order thalamic nucleus for whisking, so one article proposes it is actually another cortical region higher in the hierarchy. That does not seem to be the case, as we will see.

Barrel cortex is weird, and so is the associated higher order thalamic nucleus, POm. It is not exactly higher order. The posterior two-thirds is higher order, but it mainly projects to L1 of barrel cortex so it is not really relevant to layer 6. The anterior third is a convergence zone, neither primary nor higher order. Its cells are driven by the sensory input as well as by the barrel cortex. It projects to L1 like the nonconvergence zone, but it also projects to L5a, where slender tufted cells are located in rodents. There are multiple convergence zones in primates, but few studies acknowledge convergence zones. Convergence zones associated with primary cortex are clearly not universal. The septal parts of barrel cortex are probably driven by the convergence zone like the primary thalamus drives columns.

The convergence zone has axons in layer 5a, but that does not mean they drive slender tufted cell firing. They probably don’t because the effects of POm, although possibly just the nonconvergence zone, on the cortex are mainly metabotropic. However, POm and slender tufted cells have some things in common. Both often seem unresponsive in experiments and both are closely associated with behavior.

Those two associations are linked by behavioral gating. Slender tufted cells, albeit a small sample size, have elevated firing rates during whisking, and they project to the striatum, so they have a clear role in behavior. Meanwhile, the convergence zone (but likely not the higher order zone) of the POm is briefly inhibited by a subcortical structure called the zone incerta during sensory input. This inhibition causes the delayed responses in most experiments, and it might make the convergence zone entirely higher order because cortical responses are delayed compared to sensory inputs. However, signals from the motor cortex to the zone incerta inhibit these cells, allowing the convergence zone to respond immediately to the sensory input. That behavioral gating suggests the convergence zone causes slender tufted cells to fire more.

Whereas in upper L6 CT cells are denser in columns and CC cells are denser in septa, there is no difference in lower L6, suggesting that dual-projecting CT cells are part of a septa-linked system.

Behaviorally gated responses are a theme of this system, and so are elongated portions of the map of the sensor. Slender tufted cells have long-reaching axons in L2/3 and L6, unlike thick tufted L5 cells, and they probably drive very long receptive fields in L6 with elongated axon arbors. It just so happens that dual-projecting CT cells project to elongated portions of the thalamus. That does not mean they are driven by slender tufted cells, although that seems likely, but they are clearly part of the same system.

Corticocortical cells in L6 are strongly associated with behavior since they are probably mainly driven by the motor cortex, and they have transcolumnar axons, so they are probably related to this system in some way. They also might receive only motor signals about rotation, which could mesh with long receptive fields somehow.

Dual-projecting CT cells happen to have very long axon arbors in the primary thalamus, reminiscent of the long receptive fields in L6, so although they could easily lack those receptive fields, they are part of the same system and therefore closely associated with slender tufted cells. There is also a substantial group of CT cells which are unresponsive to any form of sensory stimulation. That is consistent with dual-projecting CT cells, which receive less thalamic input than primary CT cells, being involved in a behavior-linked system. Also, whereas in upper L6 CT cells are denser in columns and CC cells are denser in septa, there is no difference in lower L6, suggesting that dual-projecting CT cells are part of a septa-linked system but not primary CT cells. M1-projecting CC cells are denser in upper L6, so they could be septal.

Here’s the problem that started this line of thinking. The projections from dual-projecting CT cells to the primary thalamus in the whisking system form elongated axon arbors, but those arbors are not arbitrary. They’re all oriented along the vertical axis of the whisker pad (called whisker arcs), which is perpendicular to the axis along which most whisking motion occurs. That makes it seem like they serve no function. Maybe they’re just better that way for this sense. However, I doubt these axon arbors are all aligned the same way in the visual system. They have been proposed to be related to lines in the visual input, and it makes a lot of sense to modulate thalamic cells that correspond to the same feature the same way. A fixed line on the whisker pad could actually be an arbitrary line. It can only operate in terms of a whisker arc, but whiskers don’t just send a binary signal. They also detect the direction of whisker deflection, so the orientation of the feature can be arbitrary. If the elongated arbors in the visual system are arbitrary, then for whatever reason using multiple whiskers is probably required to unambiguously determine the orientation of the feature. However, that does not explain why it does not have arbors oriented in any direction on the whisker pad’s thalamic representation, since so far there seems no reason not to have those.

Consider what would happen during whisking if it had arbors oriented in any direction. The signals to the thalamus can last much longer than a whisking cycle. It can control the firing modes of cells for each whisker, but not for each place in the whisked space. There is not enough temporal precision to do so. If it tried to modulate cells oriented along the same row, it would interfere with other modulation. The whisker hits one feature and then another, but it has to have one firing mode for the whole cycle. This problem still exists for whiskers in the same arc, but it is more minor because whiskers along the same arc hit the surface around the same time.

What about when it isn’t whisking? With these arbitrarily oriented arbors, if it isn’t moving, it cannot operate in terms of other orientations of features. That means this system is only for behavior. When it is not behaving, the more normal system is sufficient. I do not know why that system lacks elongated axon arbors in the thalamus, although it might have those in visual cortex, probably on a smaller scale.

Layer 5 thick tufted cells project to the convergence zone. That might seem unnecessary since this system just needs to be gated by behavior. However, the sensory input during whisking is strongly tied to the behavior, so it makes sense to put it in context of something related to behavior. I do not think thick tufted cells just produce behavior but that’s a whole different topic.

This description of the second system includes specializations, so as described it is not in its pure form. V1 of the same species has dual-projecting CT cells (at least morphologically and in that they project to L5a), and V1 is the region where the elongated receptive fields were found, but there is no convergence zone for V1 and slender tufted cells do not receive higher order thalamic input there. V1 and barrel cortex L6 cells both receive motor copy signals, though. It is possible that combining results from these two regions (and in some cases elsewhere) could have caused problems.

Many questions about this system remain. What is the purpose of the elongated receptive fields and arbors? Does behavior just ungate this system, or does it have a crucial role in modalities with less dependence on behavior than whiskers? Why do the septal parts of barrel cortex have all the layers and are all of those divided into septal and normal? Does the septal system just solve problems unique to whisking? Are mechanisms in layer 6 for oscillations, brain states, attention, and so forth related to this? Attention kind of has to be related because it involves corticothalamic cells. Do duel-projecting CT cells only project to the convergence zone? What does the normal system do while the second system is active and can that help clarify the normal system? Is the second system universal? Are dual-projecting CT cells universal?


For Morphology and intracortical projections of functionally characterised neurones in the cat visual cortex, see

For Burst and tonic firing in thalamic cells of unanesthetized, behaving monkeys, see


  1. Beierlein M, Connors BW. Short-term dynamics of thalamocortical and intracortical synapses onto layer 6 neurons in neocortex. J Neurophysiol. 2002;88(4):1924-32.

  2. Zhou Y, Liu BH, Wu GK, et al. Preceding inhibition silences layer 6 neurons in auditory cortex. Neuron. 2010;65(5):706-17.

  3. Kinnischtzke AK, Fanselow EE, Simons DJ. Target-specific M1 inputs to infragranular S1 pyramidal neurons. J Neurophysiol. 2016;116(3):1261-74.

  4. Gilbert CD, Wiesel TN. Morphology and intracortical projections of functionally characterised neurones in the cat visual cortex. Nature. 1979;280(5718):120-5.

  5. Vélez-fort M, Bracey EF, Keshavarzi S, et al. A Circuit for Integration of Head- and Visual-Motion Signals in Layer 6 of Mouse Primary Visual Cortex. Neuron. 2018;98(1):179-191.e6.

  6. Cotel F, Fletcher LN, Kalita-de croft S, Apergis-schoute J, Williams SR. Cell Class-Dependent Intracortical Connectivity and Output Dynamics of Layer 6 Projection Neurons of the Rat Primary Visual Cortex. Cereb Cortex. 2018;28(7):2340-2350.

  7. Crandall SR, Patrick SL, Cruikshank SJ, Connors BW. Infrabarrels Are Layer 6 Circuit Modules in the Barrel Cortex that Link Long-Range Inputs and Outputs. Cell Rep. 2017;21(11):3065-3078.

  8. Zarrinpar A, Callaway EM. Local connections to specific types of layer 6 neurons in the rat visual cortex. J Neurophysiol. 2006;95(3):1751-61.

  9. Ledergerber D, Larkum ME. Properties of layer 6 pyramidal neuron apical dendrites. J Neurosci. 2010;30(39):13031-44.

  10. Zhang ZW, Deschênes M. Intracortical axonal projections of lamina VI cells of the primary somatosensory cortex in the rat: a single-cell labeling study. J Neurosci. 1997;17(16):6365-79.

  11. Groh A, Bokor H, Mease RA, et al. Convergence of cortical and sensory driver inputs on single thalamocortical cells. Cereb Cortex. 2014;24(12):3167-79.

  12. Briggs F. Organizing principles of cortical layer 6. Front Neural Circuits. 2010;4:3.

  13. Mercer A, West DC, Morris OT, Kirchhecker S, Kerkhoff JE, Thomson AM. Excitatory connections made by presynaptic cortico-cortical pyramidal cells in layer 6 of the neocortex. Cereb Cortex. 2005;15(10):1485-96.

  14. Thomson AM. Neocortical layer 6, a review. Front Neuroanat. 2010;4:13.

  15. Marx M, Feldmeyer D. Morphology and physiology of excitatory neurons in layer 6b of the somatosensory rat barrel cortex. Cereb Cortex. 2013;23(12):2803-17.

  16. Kim J, Matney CJ, Blankenship A, Hestrin S, Brown SP. Layer 6 corticothalamic neurons activate a cortical output layer, layer 5a. J Neurosci. 2014;34(29):9656-64.

  17. Landisman CE, Connors BW. VPM and PoM nuclei of the rat somatosensory thalamus: intrinsic neuronal properties and corticothalamic feedback. Cereb Cortex. 2007;17(12):2853-65.

  18. West DC, Mercer A, Kirchhecker S, Morris OT, Thomson AM. Layer 6 cortico-thalamic pyramidal cells preferentially innervate interneurons and generate facilitating EPSPs. Cereb Cortex. 2006;16(2):200-11.

  19. Polsky A, Mel B, Schiller J. Encoding and decoding bursts by NMDA spikes in basal dendrites of layer 5 pyramidal neurons. J Neurosci. 2009;29(38):11891-903.

  20. Viaene AN, Petrof I, Sherman SM. Properties of the thalamic projection from the posterior medial nucleus to primary and secondary somatosensory cortices in the mouse. Proc Natl Acad Sci USA. 2011;108(44):18156-61.

  21. Mease RA, Sumser A, Sakmann B, Groh A. Cortical Dependence of Whisker Responses in Posterior Medial Thalamus In Vivo. Cereb Cortex. 2016;26(8):3534-43.

  22. Mease RA, Metz M, Groh A. Cortical Sensory Responses Are Enhanced by the Higher-Order Thalamus. Cell Rep. 2016;14(2):208-15.

  23. Castejon C, Barros-zulaica N, Nuñez A. Control of Somatosensory Cortical Processing by Thalamic Posterior Medial Nucleus: A New Role of Thalamus in Cortical Function. PLoS ONE. 2016;11(1):e0148169.

  24. Wright N, Fox K. Origins of cortical layer V surround receptive fields in the rat barrel cortex. J Neurophysiol. 2010;103(2):709-24.

  25. Pluta SR, Lyall EH, Telian GI, Ryapolova-webb E, Adesnik H. Surround Integration Organizes a Spatial Map during Active Sensation. Neuron. 2017;94(6):1220-1233.e5.

  26. Kim J, Matney CJ, Blankenship A, Hestrin S, Brown SP. Layer 6 corticothalamic neurons activate a cortical output layer, layer 5a. J Neurosci. 2014;34(29):9656-64.

  27. Hoerder-suabedissen A, Hayashi S, Upton L, et al. Subset of Cortical Layer 6b Neurons Selectively Innervates Higher Order Thalamic Nuclei in Mice. Cereb Cortex. 2018;28(5):1882-1897.

  28. Swadlow HA. Efferent neurons and suspected interneurons in S-1 vibrissa cortex of the awake rabbit: receptive fields and axonal properties. J Neurophysiol. 1989;62(1):288-308.

  29. Swadlow HA. Efferent neurons and suspected interneurons in second somatosensory cortex of the awake rabbit: receptive fields and axonal properties. J Neurophysiol. 1991;66(4):1392-409.

  30. Swadlow HA. Efferent neurons and suspected interneurons in motor cortex of the awake rabbit: axonal properties, sensory receptive fields, and subthreshold synaptic inputs. J Neurophysiol. 1994;71(2):437-53.

  31. Swadlow HA, Hicks TP. Somatosensory cortical efferent neurons of the awake rabbit: latencies to activation via supra–and subthreshold receptive fields. J Neurophysiol. 1996;75(4):1753-9.

  32. Trageser JC, Keller A. Reducing the uncertainty: gating of peripheral inputs by zona incerta. J Neurosci. 2004;24(40):8911-5.

  33. Thomson AM. Neocortical layer 6, a review. Front Neuroanat. 2010;4:13.

  34. Marx M, Feldmeyer D. Morphology and physiology of excitatory neurons in layer 6b of the somatosensory rat barrel cortex. Cereb Cortex. 2013;23(12):2803-17.

  35. Kim J, Matney CJ, Blankenship A, Hestrin S, Brown SP. Layer 6 corticothalamic neurons activate a cortical output layer, layer 5a. J Neurosci. 2014;34(29):9656-64.

36 duplicate of 17

  1. West DC, Mercer A, Kirchhecker S, Morris OT, Thomson AM. Layer 6 cortico-thalamic pyramidal cells preferentially innervate interneurons and generate facilitating EPSPs. Cereb Cortex. 2006;16(2):200-11.

  2. Hoerder-suabedissen A, Hayashi S, Upton L, et al. Subset of Cortical Layer 6b Neurons Selectively Innervates Higher Order Thalamic Nuclei in Mice. Cereb Cortex. 2018;28(5):1882-1897.

  3. Guo W, Clause AR, Barth-maron A, Polley DB. A Corticothalamic Circuit for Dynamic Switching between Feature Detection and Discrimination. Neuron. 2017;95(1):180-194.e5.

  4. Ramcharan EJ, Gnadt JW, Sherman SM. Burst and tonic firing in thalamic cells of unanesthetized, behaving monkeys. Vis Neurosci. 2000;17(1):55-62.

  5. Connelly WM, Crunelli V, Errington AC. Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons. J Neurosci. 2017;37(21):5319-5333.

  6. Whitmire CJ, Waiblinger C, Schwarz C, Stanley GB. Information Coding through Adaptive Gating of Synchronized Thalamic Bursting. Cell Rep. 2016;14(4):795-807.

  7. Bayer L, Serafin M, Eggermann E, et al. Exclusive postsynaptic action of hypocretin-orexin on sublayer 6b cortical neurons. J Neurosci. 2004;24(30):6760-4.

  8. Maruoka H, Nakagawa N, Tsuruno S, Sakai S, Yoneda T, Hosoya T. Lattice system of functionally distinct cell types in the neocortex. Science. 2017;358(6363):610-615.

  9. Oberlaender M, Boudewijns ZS, Kleele T, Mansvelder HD, Sakmann B, De kock CP. Three-dimensional axon morphologies of individual layer 5 neurons indicate cell type-specific intracortical pathways for whisker motion and touch. Proc Natl Acad Sci USA. 2011;108(10):4188-93.

  10. Sillito AM, Jones HE, Gerstein GL, West DC. Feature-linked synchronization of thalamic relay cell firing induced by feedback from the visual cortex. Nature. 1994;369(6480):479-82.

  11. Pluta SR, Lyall EH, Telian GI, Ryapolova-webb E, Adesnik H. Surround Integration Organizes a Spatial Map during Active Sensation. Neuron. 2017;94(6):1220-1233.e5.

Things Which Don't Fit a Review (from the previous version of this post)

Things Which Don’t Fit a Review

Links to google docs for notes

From most to least recent-

Layer 6:

L5 Notes 3:

L5 Notes 2:

L5 Notes 1:

Neuroscience Notes (hippocampus, EC, and L5/6 mainly but I’m not drawing on these since they’re old):

I’d just treat the last two as sources of sources because I was newer to neuroscience, and the first three will probably take a while to work through so maybe treat those as sources of sources too.

Terminology which is potentially confusing and hard to look up

Corticothalamic Cells: Cells which project from the cortex to the thalamus.

[name 1]o[name 2]al: From [name 1] to [name 2]. Examples: corticocortical, thalamocortical, and corticospinal. The names are sometimes confusing. Retinogeniculate: from the retina to LGN, which is the primary thalamus for vision. Corticotectal or corticocollicular: from the cortex to the superior colliculus. Corticocollicular can also mean to the inferior colliculus. Corticofugal: from the cortex to outside the cortex.

These get abbreviated often. I will use these abbreviations: CC (corticocortical), TC (thalamocortical), and CT (corticothalamic).

Driver or driving: roughly speaking, a signal which can cause cells to fire without other inputs. A more exact definition is based on the properties of the synapses involved on their locations on the receiving cell.

Primary thalamus: a thalamic nucleus whose inputs from the cortex typically cannot cause cells to fire if there are no other inputs. I use it to refer to primary sensory thalamus, which receives driving inputs from the sensory input, but it can also refer to some motor nuclei, which receive driving inputs from structures like the cerebellum.


I try to take a lot of notes and look for consistencies and contradictions to minimize misinformation and make inferences about what’s going on. The main goal is to eventually generate hints towards roles of cell types.

The main challenge with neuroscience is that very few things are solid facts. Basic things, like which cell types are directly driven to spike by the thalamus, are still disputed, so it’s hard to theorize about intelligence. But neuroscience also provides a solution to its massive ambiguity, which is its massive redundancy. There are loads of studies about something new and unique, but also plenty of studies about the same thing in different regions, species, and brain states, using different techniques. This redundancy helps determine what things are part of the fundamental circuit. More importantly, it’s all part of larger circuits, so a bunch of possible facts can point towards that circuit.

I don’t like the term circuit. It implies something like a computer circuit, with discrete steps. If you look at the same transistor in each instance of a repeated circuit, you can’t really assign it a role of its own. You can only say that it does something which is meaningful for the output of the whole circuit. The cortex isn’t like that. Each layer has a bunch of inputs from and outputs to other layers, so there’s no clear flow of information. Most layers also have inputs from and outputs to other cortical or subcortical areas. The point of the cortical circuit isn’t to take an input and spit out an output. Instead, each cell type plays certain roles.

Take layer 5 for example. If I understand correctly, L5 is thought to be for relative location at Numenta. All the signs seem to point to that role. It generates motor output (a change in location) but also exists in great numbers in non-motor regions, projects up the hierarchy, has wide receptive fields on the sensor (allowing converting to location in another spatial system), has lower selectivity to details than most other excitatory cell types, and communicates with L6 and itself through far-reaching connections. That’s probably one part of a broader role not so easily expressible in words, but it’s something to build on, unlike a rigid circuit. Other ideas about roles likely led to this one, like the idea that a major role of the cortex is to handle locations on objects, so roles help determine more roles.

Roles can be expressed with a brief thought, but neuroscience has a lot of ambiguity, so it takes time to arrive at that thought. I’m not an expert at neuroscience, but it took me two years of researching layer 5 and several hundred pages of notes to produce a hypothesis about what it does (sensory onset processing for grid fields on the sensor), and that hypothesis wasn’t very good. Still, I think this approach works. I read on this forum that L5 is thought to be for displacements and misunderstood, thinking displacements were changes in location rather than relative locations of parts of the object (I could still be wrong). Based on the idea of forming grid fields on the sensor’s surface, I thought it might be for location instead of changes in location. That’s a small change, but some of the evidence for this role was my evidence for the prior hypothesis. The point is, thinking about things in terms of roles allows flexibility and building up a framework. I have wasted a lot of time by not doing that.

Thoughts about sublayers

Physical sublayers are not important to intelligence, since they are just how the cell bodies are organized. What really matters is the cell types and their processing. However, determining cell types seems to be hard, so most studies use physical sublayers to help infer cell types. Physical sublayers are a tool for interpreting results. For example, in the barrel cortex, slender tufted cells are in L5a and thick tufted cells are in L5b, so the depth in the cortical sheet indicates the cell type.

It is important to get the sublayers and their cell types right early. Layer 5 seems to have a mostly unacknowledged third cell type, not limited to one region, and it took a long time before I learned about it. That made a lot of my notes ambiguous, which I’d like to avoid repeating.

Linking physical sublayers to cell types is not straightforward. L5a and L5b are swapped or blur together in some species and regions, and it has further subdivisions at least in motor cortex, for example. In layer 6, the connection between physical depth and cell type already seems more confusing than in L5.

Are primary CT cells only in L6A in rat V1 and barrel cortex?

The apparent depth ranges are actually quite similar in (8) and (10), based on differences in their defined widths of L6Bb and whether it was included in their usages of the term L6. That suggests they are both in L6Ba.

Their depths are unclear, however, based on (8 fig. 3) and (10 fig. 2). The study which claims they are only in L6A found a small fraction of them a bit past half the depth, and they excluded different fractions of L6 as L6Bb, so they found nearly identical ranges of depths. Since they both found basket cells limited to L6A, CT cells in barrel cortex are organized into cortical columns only in L6A (7), VPM is more easily identified as a target than POm (17), and the density below L6A is much lower in the study on barrel cortex, they are probably on in L6A in barrel cortex as that study claims. The study on V1 which found them in L6A and L6Ba found a similar density in both of those sublayers, but it classified cells based on whether the apical dendrite passed into L4, which is somewhat arbitrary and therefore could produce false clusters. Also, the basket cells were still found only in L6A in V1, so overall it is unclear whether they are in L6Ba in V1.

The anchoring effect

The putative TT cells are described by an old article that has been cited over a thousand times. It’s unfortunate a single article with potential flaws can have such a large influence. I worry that drawing on this article will just amplify widespread underlying opinions. Mostly this is an excuse to talk about something relevant to research. There are probably better examples of the anchoring effect in the literature.

The first study on a topic usually has a huge impact on the field. People form opinions based on the first thing they see. For me, that makes me not want to take notes on contradicting things, not because I don’t want to have those notes, but because it’s easier and feels like more progress to build on an existing framework of knowledge.

I find it’s a good idea to throw out the first couple things you hear or read about something. Even though I try to do that, what I read first still ends up biasing me often, and sometimes there’s not much choice because not much information is available. It’s an especially big problem for abstract phenomena which seem like big hints at roles of cell types.

It doesn’t just apply to opinions about the facts like cell types. Hypotheses about roles and mechanisms are perhaps even more strongly impacted. Right now, I am heavily biased by my first idea about what layer 5 does. It involves receptive fields effectively travelling across the sensor, so the long-reaching axons from L5 into L6 and the very long receptive fields in L6 make it hard not to think about L6 in terms of that idea. That’s a major problem if my idea is a bit off the mark or plain wrong. I’ve heard it’s a good idea to keep multiple hypotheses about the same thing at any given time, which could help.

I suppose the period between the first hypothesis and the second one is a good time to lock up that first hypothesis and pretend it doesn’t exist, at least for a bit. It’s too hard not to get excited, though.

Extra credits has a good youtube video about the anchoring effect.

An attempt to assign the CT classes to two responsivity classes

A couple of studies identified a group of cells with response to sensory inputs and a group without. Both describe ambiguous classes. The unresponsive type is probably primary CT, while the responsive type is probably dual-projecting CT.

The first study (or rather, series of similar studies) is only about subcortically projecting L6 cells in awake rabbits (3). Those cells are probably corticothalamic, but I only have access to the abstracts. That series of studies is about somatosensory and motor regions, but at least in V1, there are some cells called Meynert cells which project to the superior colliculus, unusually long distances within V1, and to other regions (12). More research is required, but Meynert cells are pretty unusual and perhaps evolutionarily derived from L5, since they are near the border (12). For now, I will assume the series of studies only found CT cells.

This series of studies did not explicitly describe two groups, but it comes close. It found that a bit less than half of the examined L6 cells respond to sensory stimulation with thalamus-driven spikes, and a similar percentage in another region had subthreshold responses. That suggests there is a group of CT cells, similar in numbers to the other group rather, which receive little net excitation to sensory stimuli.

The other study only reconstructed the unresponsive cells, and they were corticothalamic (2). It might have included CC cells, but it found twice as many unresponsive cells than normal cells. They selected regular spiking cells and CC cells have phasic responses, so they probably mostly used CT cells. The reconstructions appear incomplete, especially their tufts, but they still show unresponsive cells with apical dendrites reaching lower L4, which are probably dual-projecting CT cells. The responsive cells have apical dendrites only reaching lower L5, and both appear to be normal pyramidal cells, so they are probably dual-projecting CT cells rather than primary CT cells or CC cells.

The responsive cells in this study had excitation and inhibition at the cell’s receptive field, which drove spikes. The unresponsive cells did not have spiking receptive fields, but tonal receptive fields were identified based on local field potential and EPSP components of responses. Their lack of responses was caused by inhibition arriving a couple of milliseconds earlier than their excitation, inhibiting spontaneous activity rather than causing spiking. If the unresponsive cells are primary CT cells, this is consistent with them being in L6A, which is where all basket cells are located in L6 (8, 10).

There are a few differences between the studies which suggest these are not the right classes, all of which are from the study which used anesthesia rather than awake animals. The use of anesthesia probably explains all of these differences. The similar numbers of responsive and unresponsive cells in (3) suggests two classes, but (2) found twice as many silent cells. Anesthesia reduces sensory responses, especially complex ones not directly driven by the thalamus, which probably explains why they found few normal cells. Different regions could also have different numbers of each cell type (compare barrel cortex and V1 in 8 and 10). Another difference was spontaneous activity. The studies on awake rabbits found less spontaneous activity in unresponsive cells, whereas the other study found more spontaneous activity in unresponsive cells. Since sensory input causes reduced spontaneous spiking via interneurons, and since anesthetic probably reduces spontaneous activity of interneurons, which was quite fast in (3), this difference is attributable to the different brain states. The last difference was whether they concluded that the responsive cells had monosynaptic responses to the thalamus. The study which concluded they have monosynaptic input based that on latencies, but interneurons have longer latency sensory responses in L6 than L5 and L4 (3), which probably caused confusion.

Source (2) suggests that the unresponsive cells would respond with more complex sensory stimuli than a constant tone. That does not appear to be the case, depending on how complex the stimulation must be (3), but there must be some situations in which they respond. Perhaps they simply have extremely sparse activity, consistent with them having a role in synchronizing thalamic cells which are responding to the same feature. That means dual-projecting CT cells have another role, but it must be related since their projections to the thalamus have similar properties.

Interpretation of extreme sparsity: L6 has massive capacity for connections and responses, mostly unused

If L6 CT cells synchronize thalamic cells to separate firing times for each feature, then there are many potential responses needed, but fewer will end up used. This isn’t the case for simple stimuli like lines at particular orientations, but with just a bit more complexity, the possible numbers of those features becomes massive. Therefore, L6 needs the potential to form many different synapses, but only uses a small fraction.

The long horizontal axons in L6 from L5 cells have many apparent contacts, which are close enough together to suggest that they form synapses, but few of them actually do form synapses (6). In HTM terms, these connections involve spatially large pools of potential inputs, with few of them over the permanence threshold.

There are many CT cells in L6 which do not respond to any simple stimuli. Perhaps these really do not respond at all and are reserved for things which have not yet been learned. Cells which do not correspond to any feature and therefore do not yet synchronize thalamic cells for any feature might be needed since highly selective responses are required.

This role is compatible with burst and tonic modes in the thalamus. Bursting thalamic cells could draw attention to a place in space, rather than features since they are not put into time buckets for each feature and last longer than single spikes, and then CT feedback could change the attention to what is there. There are two forms of attention, to place (both egocentric and allocentric) and to identity. L6 could contribute to both, and the reticular thalamic nucleus could be involved in selecting locations to respond since it can put cells into burst mode. This mechanism could relate to the unresponsive cells which are inhibited slightly before they are excited, perhaps showing timing sensitivity.

I still need to research the thalamus.

Arbors are often misleading but can be useful

Dendritic and axonal arbors define where inputs can arrive from. If an arbor is restricted to a certain layer, it probably sends signals to or receives from that layer. It is also possible that dendrites or axons from another layer or sublayer come into that layer, where they connect, so arbors alone can be misleading. The long horizontal axons from L6 CC cells (7) and L5 cells (6) are long but each axon synapses somewhat sparsely, for example, leading to weaker overall connections between cell types than expected. Still, arbors can hint at roles when taken in the context of other hints at roles. In HTM terms, those long reaching axons have many potential synapses but few are above permanence threshold. Which roles could involve that?

Receptive fields can be misleading

A receptive field is just a place to which a cell can respond. That doesn’t mean it always responds to something in the receptive field. Cells in the same minicolumn can have the same receptive fields, but HTM’s temporal memory shows that not all of them necessarily respond. Taking receptive fields to be straightforward can hide a lot of what’s actually going on.

It might seem like very long receptive fields are simply that, but there is probably more to it, especially since the inputs which drive those receptive fields are from L5 slender tufted cells (they’re corticostriatal and corticocortical), each of which controls a separate part of the receptive field.

For example, if I ignore my anchoring bias, perhaps they serve to generate scanning RFs. Slender tufted cells have long latency responses, so they have wide ranging latencies, so the place on the sensor determines the latency of the long RF cell’s response. That in turn could modulate the thalamus to put each feature in a separate time bucket. For the L6 long RF cells, this process is literally scanning RFs, and for the thalamic cells, this process is scanning over features.

Why dual-projecting CT cells might be the ones with very long receptive fields

Dual-projecting CT cells have stretched axon arbors in the primary thalamus (and perhaps higher order thalamus) and in L5a. Their apical dendrites are also in L5a, where slender tufted cells are located. Slender tufted cells are probably the source of the long-reaching axons from L5 to L6 (4). In barrel cortex, slender tufted cells have smaller receptive fields than thick tufted cells (24), consistent with the putative thick tufted cells in V1 having responses which are less selective for location (4). Since slender tufted cells are presynaptic to thick tufted cells but much less often the other way around, thereby being better suited to have the less advanced receptive fields, and since the L5 cells which do not target L6 as much project to the superior colliculus in one study, the cells with long lateral axons in L6 are slender tufted cells.

For these stretched axon arbors to be involved in feature detection, they must be able to orient along the axis of any feature. Depending on what constitutes a feature and how it is mapped in the primary thalamic nucleus for whiskers, dual-projecting CT cells might not meet this requirement. Their arbors are not stretched in random directions. Instead, their axon arbors in L5a and in primary thalamus are stretched along axes corresponding to the row axis on the whisker pad (10). Assuming the arbors are one cortical column or TColumn wide, then these arbors correspond to rows of whiskers (or sections of those rows), arranged from the front of the head to the back. When the rat or mouse whisks, it moves its whiskers rhythmically back and forth, so whiskers along the same row move through overlapping areas of space. That makes this potential problem more ambiguous since it might identify features as sequences of whisker contacts, or something similar. In that case, it might not need arbors wider than a row to bind features by synchronizing thalamic cells. One potential counterargument is that receptive fields in barrel cortex tend to be stretched along the row axis, perhaps simply because they have lower acuity along that axis, so the stretched axon arbors simply match that stretching. However, if the feature binding characteristic is true for primary CT cells, it is probably also true for dual-projecting CT cells. Also, one study found a map of the whisked space (25). That means their receptive fields could actually be more circular, but in the whisked space rather than in terms of which whisker contacts the surface. Since the whiskers move through much of scanned space, many along the whisker axis will contact a surface at the same place in whisked space, giving the impression of stretched receptive fields. Perhaps the stretched axon arbors serve a role in mapping the space being moved through. However, it is worth researching whether primary CT cells actually could synchronize thalamic cells which correspond to any arbitrary feature.

Facilitation in TC Connections

This section is not specifically about layer 6.

Just as L6 corticothalamic cells facilitate, some thalamocortical cells also facilitate in the same way. Input from primary thalamus to a primary region does not do so, but the input to the primary region from higher order thalamus facilitates (20). Like L6 CT cells, this facilitation continues after many spikes and the synapses involve metabotropic receptors (20). Also like signal from CT cells to the reticular thalamic nucleus (17), these metabotropic signals are probably sent to both excitatory cells and inhibitory cells (21-23). L6 CT cells seem to control the thalamus similarly to how higher order thalamus controls primary cortex, at least broadly speaking.

CT Signals to the Thalamus

It is important to keep in mind that CT cells project to the thalamus. I haven’t done much research on that in a long time so this is based on memory. All types seem to target thalamic cells distally with facilitating synapses. They control firing mode, switching cells from burst mode (when thalamic relay cells are not excited much, they respond to sensory inputs with bursts) to tonic mode (they respond with single spikes). However, CT cells also project to the reticular thalamic nucleus (sources conflict on whether or not both CT types project to the RTN, perhaps demonstrating a third CT type), which can put thalamic cells in burst mode.

Larkum 2013 & A State of Attention