 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
eLetters published in the past 21 days: Read eLetters published in the past 7, 14, 21, 30, 90, 180 days.6 eLetters published for 5 different topic sources.
Articles Letters 
- Journal Club:
Are the Boundary-Related Cells in the Subiculum Boundary-Vector Cells?- Derdikman (28 October 2009)
[Full text] [PDF]
Author Reply
- Colin Lever, et al. (13 November 2009)
- BehavioralSystemsCognitive:
Reliable Coding Emerges from Coactivation of Climbing Fibers in Microbands of Cerebellar Purkinje Neurons- Ozden et al. (26 August 2009)
[Abstract] [Full text] [PDF]
- Eric J. Lang (13 November 2009)
- Neurobiology of Disease:
Phosphorylation of Ezrin/Radixin/Moesin Proteins by LRRK2 Promotes the Rearrangement of Actin Cytoskeleton in Neuronal Morphogenesis- Parisiadou et al. (4 November 2009)
[Abstract] [Full text] [PDF]
- Javier Alegre-Abarrategui (11 November 2009)
- Neurobiology of Disease:
A Nanomedicine Transports a Peptide Caspase-3 Inhibitor across the Blood–Brain Barrier and Provides Neuroprotection- Karatas et al. (4 November 2009)
[Abstract] [Full text] [PDF]
- Turgay Dalkara, et al. (7 November 2009)
- Brief Communications:
Brain Gray Matter Decrease in Chronic Pain Is the Consequence and Not the Cause of Pain- Rodriguez-Raecke et al. (4 November 2009)
[Abstract] [Full text] [PDF]
- Luke A Henderson (7 November 2009)
- Denson G. Fujikawa, et al. (5 November 2009)
Journal Club:
Are the Boundary-Related Cells in the Subiculum Boundary-Vector Cells?
Derdikman (28 October 2009)[Full text] [PDF]
Are the Boundary-Related Cells in the Subiculum Boundary-Vector Cells?
Author Reply13 November 2009 
Colin Lever
Behavioural Neuroscience Lab, Institute of Psychological Sciences, University of Leeds, Leeds, LS,
Stephen Burton, Ali Jeewajee, John O’Keefe, and Neil BurgessSend letter to journal:
Re: Author Reply
c.lever{at}leeds.ac.uk Colin Lever, et al.
Further to providing a helpful background sketch and summary of our report on boundary vector cells (BVCs) in the subiculum (Lever et al, 2009), Derdikman (2009) makes three contributions.
First, Derdikman attempts to reveal the underlying vector properties of BVCs, by converting environment-centred (allocentric) firing rate maps of selected BVCs from our report, into rat-centred (egocentric) boundary-to-rat rate plots (Derdikman, 2009, Fig 1A, B). This is an interesting and helpful contribution to our study. However, his approach estimates a separate receptive field for each BVC in each environment, which does not sufficiently constrain the solution to this inverse problem. For instance, in a 60x60cm square a firing field taking the form of an east-west stripe peaked at 10cm south of the north wall may indicate that the cell responds best to a boundary 10cm to the north, or, alternatively, to a boundary 50cm to the south. Simultaneously fitting data from multiple environments of different sizes would provide a better constrained solution, while also reducing the impact of “noisy” (i.e., inconsistent from trial to trial) firing. As noted by Derdikman, circular environments are particularly informative in deriving the angular component of the boundary vector response (see Derdikman, 2009, Fig. 1B central columns).
Second, Derdikman takes issue with our interpretation that BVCs may provide input into the hippocampus. He argues that subicular BVCs “may be linear sums of place cell outputs, such that their properties can be derived from the properties of place-cells, and not vice-versa”, and in concluding suggests that “the role of the boundary -related cells in the subiculum is to pass information about boundaries, stored in the hippocampus, back to the entorhinal cortex”. However, our environments and protocol were purposely designed to produce very strong CA1 place cell remapping. As we noted (Lever et al., 2009, p.9772), across-trial spatial correlations were high for CA1 place cells in 5 rats across the same environment (mean r = 0.8 for environment a-to-a comparisons) but near zero for environment a-to-b and environment a-to-c comparisons. BVCs were simultaneously recorded in 4 of these 5 rats, and maintained a constant BVC firing pattern across the three environments a-c, uninfluenced by the total reorganization of CA1 firing. Sharp (1997) also provides evidence of scenarios where subicular cells fire predictably while CA1 cells strongly remap. Thus, in these experiments at least, the CA1 input to subiculum appears to have no significant functional impact, despite the presence of a strong anatomical connection. Specifically, the BVCs are not acting as a hippocampal output.
Third, Derdikman queries the relationship between current characterisations of entorhinal ‘border cells’ (Solstad et al, 2008) and ‘BVC’s (Hartley et al, 2000; Lever et al, 2002). We note that a border cell firing along all walls is not necessarily “an obvious contradiction to the concept of a boundary vector cell”. Such a cell is not a BVC, but can be modelled in the BVC framework by changing a single parameter, directional-tuning width, to 360°. Appreciating this may have consequences for interpreting information flow within the hippocampal formation. Equally, cells classified as border cells with peak firing extending along only 20% of a boundary (e.g Solstad et al, 2008, Fig 3B, cell 201) cannot be BVCs themselves, but might reflect the input of multiple subicular BVCs, in the same way that we originally envisaged a place cell’s firing to reflect the input of multiple BVCs (Hartley et al, 2000). Derdikman asks if some subiculum boundary- related cells are border cells without boundary-vector properties. This could be so. In the dorsal subicular region we sampled, only a quarter of principal cells were BVCs.
References
Hartley T, Burgess N, Lever C, Cacucci F, O'Keefe J (2000) Modeling place fields in terms of the cortical inputs to the hippocampus. Hippocampus 10:369-379.
Lever C, Burgess N, Cacucci F, Hartley T, O'Keefe J (2002) What can the hippocampal representation of environmental geometry tell us about Hebbian learning? Biol Cybern 87:356-372.
Lever C, Burton S, Jeewajee A, O'Keefe J, Burgess N (2009). Boundary vector cells in the subiculum of the hippocampal formation. Journal of Neuroscience, 29: 9771-9777
Sharp PE (1997) Subicular cells generate similar spatial firing patterns in two geometrically and visually distinctive environments: comparison with hippocampal place cells. Behav Brain Res 85:71-92.
Solstad T, Boccara CN, Kropff E, Moser MB, Moser EI (2008) Representation of geometric borders in the entorhinal cortex. Science 322:1865-1868.
BehavioralSystemsCognitive:
Reliable Coding Emerges from Coactivation of Climbing Fibers in Microbands of Cerebellar Purkinje Neurons
Ozden et al. (26 August 2009)[Abstract] [Full text] [PDF]
Eric J. Lang,
Associate Professor
New York University, School of MedicineSend letter to journal:
Re: Functional imaging confirms principles of cerebellar functioning found with multi-site recording
eric.lang{at}nyumc.org Eric J. Lang
Using new imaging techniques Ozden et al. (2009) confirmed many results previously obtained with electrophysiological methods: CS synchrony depends on gap junctions between inferior olive (IO) neurons (Blenkinsop and Lang 2006; Marshall et al., 2007); CS synchrony occurs among discrete groups of Purkinje cells (PCs) and thus does not decrease smoothly with distance (Sugihara et al., 2007); spontaneous and evoked CS synchrony patterns are largely congruent (Llinás and Sasaki, 1989; Lang, 2002); and stimuli elicit rhythmic CS discharges (Puro and Woodward, 1977; Bloedel and Ebner, 1984; Llinás and Sasaki, 1989; and others). This original work should have been acknowledged.
One seemingly new finding of significance was that synchrony "in neighboring PCs is an order of magnitude larger than reported previously from more sparse sampling methods", implying prior studies missed this localized region of high synchrony because of the spacing of electrodes in multielectrode arrays (typically 250 µm). However, this reasoning ignores the two-dimensional structure of the arrays: multiple PCs are recorded in- line with each other within particular parasagittal planes, and thus can form in-line cell pairs, which are separated by ~0 µm along the mediolateral axis (Fig. 1A, below). These in-line cell pairs are separated by ≥250 µm rostrocaudally, but Ozden et al. agree that synchrony tapers more slowly in that direction. Thus, in-line pairs of multielectrode arrays are a subset of the "neighboring PC" population sampled in its entirety by Ozden et al. Therefore, the synchrony levels of the two populations should be consistent, barring some unlikely sampling bias.
A more probable explanation is that the apparent discrepancy is due to technical factors, including the two described below. First, average CS synchrony levels vary across the cerebellum. In particular, higher levels occur on medial than lateral crus 2a (.138 vs. .05; Sugihara et al., 2007), and Ozden et al. may have recorded from medial crus 2a (their specific recording site on crus 2a is not specified, but the widths of their "microbands" correspond to the narrow zebrin compartments found in medial crus 2a). Second, Ozden et al. used different definitions of synchrony. Most prior work has quantified CS synchrony using the height of the central 1-ms bin of the cross-correlogram, whereas Ozden et al. used bins ranging from four to several hundred milliseconds because of the temporal resolution limitations of their imaging system. Using 4 or 20 ms bins our synchrony values generally increase 2-4 fold. In particular, with such bin sizes, our in-line pairs show essentially the same range of synchrony values as those given by Ozden et al. (Fig. 1B,C, below). Thus, Ozden et al.'s findings on local synchrony are actually consistent with prior results. They also extend them in that prior studies used statistical inference based on a small sample of the population to conclude that CS synchrony bands were solid entities, whereas Ozden et al. have demonstrated this directly by recording the entire local PC population.
Figure 1. Effect of bin size on CS synchrony. (A) Scheme showing zebrin staining of crus 2a region where multielectrode recording was performed. Red dots indicate electrode locations. Spacing between neighboring electrodes is 250 µm. Black lines show in-line cell pairs for compartment 5-. (B-C) CS synchrony was calculated for all in-line cell pairs using 1, 4, or 20-ms bins. The synchrony distributions are plotted for the different bin widths for all in-line pairs (B) and for those in compartment 5- only (C). Large blue circles indicate average in each condition. The vertical red bar indicates the interquartile range of Ozden et al. (2009). Note the similarity to the spread of synchrony values obtained with 20-ms bins.
References
Blenkinsop TA, Lang EJ (2006) Block of inferior olive gap junctional coupling decreases Purkinje cell complex spike synchrony and rhythmicity. J Neurosci 26:1739-1748.
Bloedel JR, Ebner TJ (1984) Rhythmic discharge of climbing fibre afferents in response to natural peripheral stimuli in the cat. J Physiol (Lond) 352:129-146.
Lang EJ (2002) GABAergic and glutamatergic modulation of spontaneous and motor-cortex-evoked complex spike activity. J Neurophysiol 87:1993- 2008.
Llinás R, Sasaki K (1989) The functional organization of the olivo- cerebellar system as examined by multiple Purkinje cell recordings. Eur J Neurosci 1:587-602.
Marshall SP, Van der Giessen RS, De Zeeuw CI, Lang EJ (2007) Altered olivocerebellar activity patterns in the connexin36 knockout mouse. Cerebellum 6:287-299.
Ozden I, Sullivan MR, Lee HM, Wang SS (2009) Reliable coding emerges from coactivation of climbing fibers in microbands of cerebellar Purkinje neurons. J Neurosci 29:10463-10473.
Puro DG, Woodward DJ (1977) Maturation of evoked climbing fiber input to rat cerebellar Purkinje cells. Exp Brain Res 28:85-100.
Sugihara I, Marshall SP, Lang EJ (2007) Relationship of complex spike synchrony to the lobular and longitudinal aldolase C compartments in crus IIA of the cerebellar cortex. J Comp Neurol 501:13-29.
Neurobiology of Disease:
Phosphorylation of Ezrin/Radixin/Moesin Proteins by LRRK2 Promotes the Rearrangement of Actin Cytoskeleton in Neuronal Morphogenesis
Parisiadou et al. (4 November 2009)[Abstract] [Full text] [PDF]
Phosphorylation of Ezrin/Radixin/Moesin Proteins by LRRK2 Promotes the Rearrangement...
LRRK2 localizes to filopodia11 November 2009 Javier Alegre-Abarrategui,
Postdoctoral research scientist
Department of Physiology, Anatomy and Genetics. University of Oxford. OX1 3QXSend letter to journal:
Re: LRRK2 localizes to filopodia
javier.alegre{at}dpag.ox.ac.uk Javier Alegre-Abarrategui
This very interesting report by Parisiadou et al. shows that LRRK2-mediated phosphorylation of ERM proteins modifies the number of p-ERM-positive and F-actin-enriched filopodia. The authors recognize that, at the subcellular level, where and when LRRK2 modifies the phosphorylation state of ERM proteins remains elusive. Because they are only able to detect LRRK2 protein in the cellular soma, they hypothesize that phosphorylation happens in the cytosol and the resulting pERM is then transported to filopodia.
We have recently demonstrated that membrane-associated LRRK2 protein is recruited to filopodia/microvilli upon the formation of these structures, as well as other structures known to be enriched in ERM proteins (Alegre-Abarrategui et al., 2009; Alegre-Abarrategui and Wade- Martins, 2009). These results were achieved by using a novel genomic reporter cellular model to express a YPet-LRRK2 protein from the genomic locus in combination with immunoelectron microscopy. Based on our results, we believe that ERM protein phosphorylation occurs in filopodia upon the active recruitment of LRRK2, which is consistent with the hypothesis that phosphorylated ERM proteins specifically accumulate in filopodia and not in the cytosol (Nakamura et al., 2000).
Alegre-Abarrategui J, Christian H, Lufino MM, Mutihac R, Venda LL, Ansorge O, Wade-Martins R (2009) LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet 18:4022-4034.
Alegre-Abarrategui J, Wade-Martins R (2009) Parkinson disease, LRRK2 and the endocytic-autophagic pathway. Autophagy 5.
Nakamura N, Oshiro N, Fukata Y, Amano M, Fukata M, Kuroda S, Matsuura Y, Leung T, Lim L, Kaibuchi K (2000) Phosphorylation of ERM proteins at filopodia induced by Cdc42. Genes Cells 5:571-581.
Neurobiology of Disease:
A Nanomedicine Transports a Peptide Caspase-3 Inhibitor across the Blood–Brain Barrier and Provides Neuroprotection
Karatas et al. (4 November 2009)[Abstract] [Full text] [PDF]
A Nanomedicine Transports a Peptide Caspase-3 Inhibitor across the Blood–Brain Barrier...
Re: Z-DEVD-fmk inhibits calpain I (author's reply)7 November 2009 Turgay Dalkara,
Professor of Neurology
Department of Neurology, Faculty of Medicine, Hacetepe University,
Ankara, Turkey 06100Send letter to journal:
Re: Re: Z-DEVD-fmk inhibits calpain I (author's reply)
tdalkara{at}hacettepe.edu.tr Turgay Dalkara, et al.
As pointed out by Dr. Fujikawa and as we also indicated in the Abstract and Introduction of the paper, Z-DEVD-fmk is a relatively specific inhibitor of caspase-3. However, since Z-DEVD-fmk potently inhibits caspase-3 activity, we used it as a reporter to test whether or not systemically administered nanospheres delivered sufficient amounts of Z-DEVD-fmk to the brain. Alternative assays might also be considered but we preferred caspase-3 activity because the time course of caspase-3 activation during ischemia/reperfusion and its inhibition by Z-DEVD-fmk had been well characterized in the mouse ischemia/reperfusion model that we used (Namura et al., 1998; Ma et al., 1998; Ma et al., 2001).
As indicated by Dr. Fujikawa and as has been shown by several laboratories including ours, the ischemic cell death is complex and involves activation of several proteases including caspases, cathepsins and calpains (Unal-Cevik et al., 2004; Lo et al., 2003; Dalkara and Moskowitz, 2004). Therefore, the aim of our present study was not to provide further insight to cell death mechanisms after transient middle cerebral artery occlusion (tMCAO) but to use tMCAO as a model for testing the efficiency of the nanomedicine- transported peptide delivery. Moreover, we evaluated the efficiency of nanospheres to transport Z-DEVD-fmk across BBB not only in a tMCAo model but also in a developmental cell death model, in which caspase-3 plays a more prominent role (Figure 5).
References:
1) Namura S, Zhu J, Fink K, Endres M, Srinivasan A, Tomaselli KJ, Yuan J, Moskowitz MA (1998) Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci 18:3659 –3668.
2) Ma J, Endres M, Moskowitz MA (1998) Synergistic effects of caspase inhibitors and MK-801 in brain injury after transient focal cerebral ischaemia in mice. Br J Pharmacol 124:756 –762.
3) Ma J, Qiu J, Hirt L, Dalkara T, Moskowitz MA (2001) Synergistic protective effect of caspase inhibitors and bFGF against brain injury induced by transient focal ischaemia. Br J Pharmacol 133:345–350.
4) Unal-Cevik I, Kilinc M, Can A, Gursoy-Ozdemir Y, Dalkara T (2004) Apoptotic and necrotic death mechanisms are concomitantly activated in the same cell after cerebral ischemia. Stroke 35(9):2189-2194.
5) Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4(5):399-415.
6) Dalkara T, Moskowitz MA (2004) Apoptosis in cerebral ischemia. In: Mohr JP, Choi D, Grotta JC, Weir B, Wolf PA, eds. Stroke: Pathophysiology, Diagnosis and Management. Philadelphia: Churchill Livingstone. pp:855-866.
Brief Communications:
Brain Gray Matter Decrease in Chronic Pain Is the Consequence and Not the Cause of Pain
Rodriguez-Raecke et al. (4 November 2009)[Abstract] [Full text] [PDF]
Brain Gray Matter Decrease in Chronic Pain Is the Consequence and Not the Cause...
Grey matter changes in chronic nociceptive pain conditions are reversible7 November 2009 Luke A Henderson,
Senior Lecturer
University of Sydney, 2006Send letter to journal:
Re: Grey matter changes in chronic nociceptive pain conditions are reversible
lukeh{at}anatomy.usyd.edu.au Luke A Henderson
In a recent publication by Rodriguez-Raecke and colleagues it was reported that regional grey matter losses associated with osteoarthritic pain are reversed following hip replacement and subsequent pain relief. The authors suggest that grey matter changes are a consequence, not the cause of chronic nociceptive pain. Although this is possible, the data presented precludes this interpretation, since the grey matter changes were directly associated with the presence of pain i.e. if pain was perceived, then regional grey matter volumes were reduced. Indeed the most parsimonious explanation is that grey matter changes underlie the perception of pain as when pain was relieved, regional grey matter returned towards control levels in a sub-group of patients. More importantly, the data presented suggests that the changes in regional brain structure associated with chronic nociceptive pain can be reversed if the source of increased afferent drive is stopped. This is an important finding and suggests that future treatment regimes which aim to reverse the anatomical changes associated with other types of chronic pain, such as neuropathic pain, may also be effective at relieving pain.
Brain Gray Matter Decrease in Chronic Pain Is the Consequence and Not the Cause...
Z-DEVD-fmk inhibits calpain I5 November 2009 Denson G. Fujikawa,
UCLA Professor of Neurology
VA GLAHS, 16111 Plummer Street,
North Hills, CA 91343Send letter to journal:
Re: Z-DEVD-fmk inhibits calpain I
dfujikaw{at}ucla.edu Denson G. Fujikawa, et al.
This article is a breakthrough in drug delivery and is therefore of great importance. However, to imply that it is caspase-3 that is being inhibited is premature. Z-DEVD-fmk also inhibits calpain I (Knoblach et al., 2004) and cathepsins (Roszman-Pungercar et al., 2003), and it is calpain I inhibition that is more important than caspase-3 inhibition in adult rodents (Hu et al., 2000; Liu et al., 2004; C. Zhu et al., 2005). Karatas et al. showed inhibition of Ac-DEVD-AMC cleavage with Z-DEVD-fmk, but since calpain I is inhibited by Z-DEVD-fmk, they might be inhibiting calpain I. To show that it is calpain I and not caspase -3 that is activated following tMCAO, one could do a calpain activity assay using Ac-LLY-AFC to see if there is an increase in activity and if it is inhibited with the calpain inhibitor Z-Leu-Leu-Tyr-FMK.
References
Knoblach SM, Alroy DA, Nikolaeva M, Cernak I, Stoica BA, Faden AI(2004) Caspase inhibitor z-DEVD-fmk attenuates calpain and necrotic cell death in vitro and after traumatic brain injury. J Cereb Blood Flow Metab. Oct;24(10):1119-32.
Rozman-Pungercar J, Kopitar-Jerala N, Bogyo M, Turk D, Vasiljeva O, Stefe I, Vandenabeele P, Brömme D, Puizdar V, Fonović M, Trstenjak-Prebanda M, Dolenc I, Turk V, Turk B. (2003) Inhibition of papain-like cysteine proteases and legumain by caspase-specific inhibitors: when reaction mechanism is more important than specificity. Cell Death Differ. Aug;10(8):881-8.
Hu BR, Liu CL, Ouyang Y, Blomgren K, Siesjö BK (2000) Involvement of caspase-3 in cell death after hypoxia-ischemia declines during brain maturation. J Cereb Blood Flow Metab. Sep;20(9):1294-300.
Liu CL, Siesjö BK, Hu BR (2004) Pathogenesis of hippocampal neuronal death after hypoxia-ischemia changes during brain development. Neuroscience 127(1):113-23.
Zhu C, Wang X, Xu F, Bahr BA, Shibata M, Uchiyama Y, Hagberg H, Blomgren K. (2005) The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia. Cell Death Differ. Feb;12(2):162-76.
|
|
|
|
 |
|