Neuroscience

Dendritic osmosensors modulate activity-induced calcium influx in oxytocinergic magnocellular neurons of the mouse PVN

1. Wanhui Sheng
2. Scott W Harden
3. Yalun Tan
4. Eric G Krause
5. Charles J Frazier

Reviewed by eLife

Rapid recycling of glutamate transporters on the astroglial surface

1. Piotr Michaluk
2. Janosch Peter Heller
3. Dmitri A Rusakov

• Curated by eLife

  Summary: In this study, Michaluk et al. examined the membrane dynamics of the main glial glutamate transporter GLT1 in hippocampal astrocytes, which was previously shown to shape synaptic transmission through regulating extracellular levels of glutamate. Using GLT1 tagged on its surface with a pH-sensitive fluorescent marker, GLT1-SEP, the authors performed (1) fluorescence recovery after photobleaching (FRAP) experiments to assess the basal and activity-dependent dynamics of surface GLT1-SEP and (2) super-resolution dSTORM imaging to determine the relationship between GLT1 and PSD-95, an excitatory synapse marker. A large proportion of surface GLT1-SEP underwent turnover with a surface lifetime of 22 s, whereas a smaller fraction (~25%) remained largely immobile, which was decreased upon increased activity. Notably, the cytoplasmic domain of GLT1-SEP was shown to attenuate the basal turnover of surface GLT1 and to facilitate its proximal localization to synapses; moreover, GLT1 cytoplasmic domain was required for activity-dependent increase in the mobile fraction.

  While previous studies using single molecule tracking have demonstrated a role for the lateral diffusion of GLT1 in controlling the recruitment of GLT1 near active synapses, the present study uses powerful optical approaches and analysis tools to access both the surface lateral mobility and the exchange between surface and intracellular pools of GLT1. Furthermore, characterization of the nanoscale organization of GLT1 relative to synapses and its dependence on the C-terminal domain of GLT1 is presented. Altogether, the results are interesting and valuable, and underscore the importance of the GLT1 C-terminus in the membrane turnover and in the activity-dependent lateral diffusion of the surface GLT1. Nevertheless, some of the conclusions are not strongly supported by the data shown.

  Reviewer #2 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife

Inhibitory control of frontal metastability sets the temporal signature of cognition

1. Vincent Fontanier
2. Matthieu Sarazin
3. Frederic M Stoll
4. Bruno Delord
5. Emmanuel Procyk

• Curated by eLife

  Summary: Both reviewers found this study's findings to be interesting and novel, and they appreciated the integration of intrinsic timescale analysis, coding of behavioral signals, and exploration of mechanisms in a biophysical circuit model. However, they both raised serious concerns about methodological and interpretational aspects of the analyses which would need to be satisfactorily addressed in subsequent review. In consultation, both reviewers were in agreement with all points raised in the other's review. I view the two reviewers' requests and suggestions as appropriate and complementary, and all of them needed response.

  I highlight here two of the major concerns raised by the reviewers (but all raised by the reviewers merit addressing). First is the need for intrinsic timescale analysis to not be confounded by slowly varying changes in firing rate coding task variables (Point 1.2 of Reviewer 2). This is important for interpretation on intrinsic timescale and its correlation with task variable coding as a major result. Second is the interpretation and implementation of Hidden Markov Models to non-simultaneously recorded neurons (Points 6 of Reviewer 1 and 3 of Reviewer 2). Here again the HMM states may be driven by task variable coding which is not corrected for, which could confound interpretation of results as in terms of meta-stable states and its link to the circuit model. Furthermore, HMM analysis of the circuit model does not match its methodology for experimental data, but could be through non-simultaneous model spike trains, which the manuscript does not justify. I will add my own suggestion that perhaps both of these methodological data analysis concerns could potentially be addressed through comparison to the null model of a non-homogeneous Poisson process with firing rate given by the variable-coding PSTH. I do not consider it necessary to study a network model that performs the task, as suggested for consideration by Reviewer 1.

Reviewed by eLife

Predominantly linear summation of metabotropic postsynaptic potentials follows coactivation of neurogliaform interneurons

1. Attila Ozsvár
2. Gergely Komlósi
3. Gáspár Oláh
4. Judith Baka
5. Gábor Molnár
6. Gábor Tamás

• Curated by eLife

  Evaluation Summary:

  This manuscript provides quantitative information of the integration of GABA-A and GABA-B receptor inhibitory responses in cortical pyramidal neurons induced by a presynaptic GABAergic neuron type called neurogliaform cell (NGFC). Experimental and modeling data suggest that NGFCs converge onto postsynaptic neurons with sublinear summation of ionotropic GABA-A potentials and linear summation of metabotropic GABA-B potentials probably due to a preferential spatial distribution of GABA-B receptor-GIRK clusters on the dendritic spines of postsynaptic neurons. The data represent an attempt to gain insights into the logic of GABA volume transmission within cortical microcircuits.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Graded spikes differentially signal neurotransmitter input in cerebrospinal fluid contacting neurons of the mouse spinal cord

1. Emily Johnson
2. Marilyn Clark
3. Merve Oncul
4. Andreea Pantiru
5. Claudia MacLean
6. Jim Deuchars
7. Susan A. Deuchars
8. Jamie Johnston

• Curated by eLife

  Summary: The reviewers have found the topic of your study of high interest, with very intriguing findings on the different origins of calcium transients in CSFcNs.

  However, after a careful examination of your work , the reviewers have raised the following major concerns:

  1. To conclude on calcium spikes, the imaging data without electrophysiological calibration leaves too much unknown. A careful electrophysiological examination should reveal how calcium transients of different amplitude correlate with the electrical activity of the cell, calcium spikes and spontaneous PKD2L1 channel openings as described extensively in these cells, is absolutely mandatory to conclude.

  2. The manuscript shows a lack of consideration of the importance of the sensory functions and of the role of channel PKDL1 that are both well-established in CSFcNs in mice and other models. More work is necessary to relate to these critical aspects.

  3. The number of animals for juvenile and adult mice used by the authors should be clearly stated (the manuscript only refers to the total number) but also largely increased for the authors to reach robust conclusions.

  4. Overall, more rigor should be implemented throughout the entire manuscript, with a deep writing improvement and a careful inspection of figure panels (choice and fair / complete representation of the data) and more information on conditions used for experiments (promoter used, concentrations for pharmacological agents, selection of ROIs, ventral versus dorsal CSF-cNs, definition and proportion of silent cells, enrichment in the T and L type calcium channels, etc ... ).

  Reviewer #2 and Reviewer #4 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife

Bacterial diet affects the age-dependent decline of associative learning in Caenorhabditis elegans

1. Satoshi Higurashi
2. Sachio Tsukada
3. Binta Maria Aleogho
4. Joo Hyun Park
5. Yana Al-Hebri
6. Masaru Tanaka
7. Shunji Nakano
8. Ikue Mori
9. Kentaro Noma

Reviewed by eLife

An expanding manifold in transmodal regions characterizes adolescent reconfiguration of structural connectome organization

1. Bo-yong Park
2. Richard AI Bethlehem
3. Casey Paquola
4. Sara Larivière
5. Raul Rodríguez-Cruces
6. Reinder Vos de Wael
7. Neuroscience in Psychiatry Network (NSPN) Consortium
8. Edward Bullmore
9. Raymond Dolan
10. Ian Goodyer
11. Peter Fonagy
12. Peter Jones
13. Michael Moutoussis
14. Tobias Hauser
15. Sharon Neufeld
16. Rafael Romero-Garcia
17. Michelle St Clair
18. Petra Vértes
19. Kirstie Whitaker
20. Becky Inkster
21. Gita Prabhu
22. Cinly Ooi
23. Umar Toseeb
24. Barry Widmer
25. Junaid Bhatti
26. Laura Villis
27. Ayesha Alrumaithi
28. Sarah Birt
29. Aislinn Bowler
30. Kalia Cleridou
31. Hina Dadabhoy
32. Emma Davies
33. Ashlyn Firkins
34. Sian Granville
35. Elizabeth Harding
36. Alexandra Hopkins
37. Daniel Isaacs
38. Janchai King
39. Danae Kokorikou
40. Christina Maurice
41. Cleo McIntosh
42. Jessica Memarzia
43. Harriet Mills
44. Ciara O’Donnell
45. Sara Pantaleone
46. Jenny Scott
47. Beatrice Kiddle
48. Ela Polek
49. Pasco Fearon
50. John Suckling
51. Anne-Laura van Harmelen
52. Rogier Kievit
53. Sam Chamberlain
54. Edward T Bullmore
55. Boris C Bernhardt

• Curated by eLife

  Summary: This manuscript describes a longitudinal study of the adolescent structural connectome. Park et al. report on an analysis of existing semi-longitudinal NSPN 2400 data to learn how the projections of high-dimensional structural connectivity patterns onto a three dimensional subspace change with age during adolescence. They employ a non-linear manifold learning algorithm (diffusion embedding), thereby linking the maturation of global structural connectivity patterns to an emerging approach in understanding brain organization through spatial gradient representations. The authors find strong effects of expansion of structural connectomes in transmodal brain regions during adolescence. They also report findings centered on the caudate and thalamus, and supplement the structural connectivity analyses with transcriptome association analyses revealing genes enriched in specific brain regions. Finally, intelligence measures are predicted from baseline structural measures.

  This is an interesting and comprehensive set of analyses on an important topic. Overall, the figures are lovely. The sensitivity analyses are particularly commendable. The paper is well written, the data are fantastic, and the analyses are interesting. Some suggestions and points for clarification (both theoretical and methodological) are below.

  Reviewer #3 opted to reveal their name to the authors in the decision letter after review.

Reviewed by eLife

Functional specialization within the inferior parietal lobes across cognitive domains

1. Ole Numssen
2. Danilo Bzdok
3. Gesa Hartwigsen

• Curated by eLife

  Summary: Overall the reviewers felt that the manuscript had a fair amount of promise but raised some issues about the specific tasks used and some details of the analysis. One reviewer in particular felt that the manuscript should be reworked around the functional connectivity results, which would strengthen the manuscript. I tend to agree with this assessment, particularly as concerns the lateralization framing which is not very well explored by these tasks.

Reviewed by eLife

Spatial modulation of visual responses arises in cortex with active navigation

1. E Mika Diamanti
2. Charu Bai Reddy
3. Sylvia Schröder
4. Tomaso Muzzu
5. Kenneth D Harris
6. Aman B Saleem
7. Matteo Carandini

• Curated by eLife

  Summary: This paper investigates the modulation of spatial signals in higher order visual areas in mice navigating virtual reality environments. Previous work demonstrated that the spatial position of an animal modulates neural activity in the primary visual cortex (V1). Here, the authors demonstrate that this spatial modulation however, is not a general feature of the visual circuit. Similar spatial modulation occurs in higher visual areas but not in lower visual areas, such as the lateral geniculate nucleus. Moreover, this work finds that spatial modulation was stronger when animals had more experience on the track and when the animals were actively performing a task, rather than when the animal was passively viewing the same virtual track. Since the first reports that visual neurons show modulation by spatial position during spatial navigation tasks, similar to that observed in hippocampal place cells, the source of this modulation has been an open question. This work adds new insight regarding this question, suggesting that it is likely either generated within the visual cortex itself or propagated in a top-down manner from higher brain areas, rather than in a bottom-up manner from the thalamus.

Reviewed by eLife

Effects of order on memory of event times

1. Michelangelo Naim
2. Mikhail Katkov
3. Misha Tsodyks

Reviewed by eLife