Molnár Lab

Today we welcomed 4 new members to our laboratory. Beatriz Campos Codo, Ruoqi Yuan, Stanley Say and Sofia Luchanskaya.

The 2024 Burdon Sanderson Prize Lecture is to be given by Professor Masashi Yanagisawa M.D., Ph.D., University of Tsukuba in Japan and University of Texas Southwestern Medical Centre in USA on Tuesday 22nd October at 4 pm in the Blakemore Lecture Theatre, Sherrington Building.

Oxford Autumn School in Neuroscience 2024
Mon 7 Oct 2024 9:15 AM - Tue 8 Oct 2024 4:30 PM
Goss Lecture Theatre, Medical Sciences Teaching Centre, South Parks Road, Oxford., OX1 3PL
Registration: https://www.tickettailor.com/events/oxfordneuroscience/1305040

The first session will be on BRAIN DEVELOPMENT:
Monday 7th October
09.15 Welcome: Professor Masud Husain, Chair Autumn School in Neuroscience

Brain Development - Chair: Professor Zoltán Molnár, Department of Physiology, Anatomy, and Genetics, University of Oxford

09.30 - 10.10 Professor Željka Krsnik, University of Zagreb School of Medicine

Early regional patterning and laminar dynamics in the developing human prefrontal cortex

10.10 - 10.50 Dr Linna Zhou, Ludwig Institute for Cancer Research, University of Oxford

3D printing cortical columns

10.50 - 11.30 Professor Rebeccah Slater, Department of Paediatrics, University of Oxford

Understanding the mechanisms that drive the development of pain perception in the human infant

11.30 - 12.10 Madeleine Wyburd, Department of Computer Science, University of Oxford

Automated grading of fetal cortical development using deep-learning algorithms from 3D ultrasound scans

Was delighted to attend the Annual Meeting of the Scientific and Social Advisory Board of the Count Istvan Tisza Foundation for the University of Debrecen. of Debrecen

Jenkinson Developmental Biology Symposium, at the MSTC, on 13 Dec 2024. Registration will open in the next few weeks: please note that registration will be mandatory but free of charge.

Neuroserpin, a secreted protein that belongs to the serpin superfamily of serine protease inhibitors, is highly expressed in the central nervous system and plays multiple roles in brain development and pathology. As a natural inhibitor of recombinant tissue plasminogen activator, neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia. We studied the neuroprotective effects of neuroserpin in adult. https://journals.lww.com/nrronline/abstract/9900/neuroserpin_alleviates_cerebral.502.aspx
Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia, initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis, which was followed by a later apoptotic response. Notably, ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons. Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules, the reduction in protein synthesis, and the upregulation of apoptotic transcription factors. This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion, as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion. However, the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin. Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress. doi.org/10.4103/NRR.NRR-D-24-00044
Lei Shi was awarded a Royal Society Newton Advanced Fellowship, No. AOMSNAF0051003,in collaboration with Molnár Lab, Department of Physiology, Anatomy and Genetics, University of Oxford (2017–2021).

HUMAN CEREBRAL CORTEXDEVELOPMENT III - OXFORDSummer meeting of the Anatomical Society14-16th July 2025, St John’s College, OxfordCo-Chairs Gavin Clowry & Zoltán Molnár
The symposium will be main focus of the meeting, allocated almost two complete days, alongside with the usual sessions on imaging and education. We are delighted that we can have a conference at this level on human cortical development.

The symposium will explore various aspects of human cortical development, including cellular and molecular mechanisms regulating cell number and diversity, migration and circuit assembly from the beginning of cortical plate formation until birth. We have selected speakers to invite from around the world who will describe how advances in developmental neurobiology, organoids, transcriptomics and imaging are offering new insights into the mechanisms controlling the development of the human cerebral cortex, as well as the developmental abnormalities and clinical advances.
This symposium is a follow up to two highly successful meetings in 2010 and in 2018 together with the acclaimed issues of the Journal of Anatomy http://onlinelibrary.wiley.com/doi/10.1111/joa.2010.217.issue-4/issuetoc and https://onlinelibrary.wiley.com/toc/14697580/2019/235/3

Please hold the date for the next CORTICAL DEVELOPMENT MEETING in Giardini Naxos, Sicily, Italy - May 25-28, 2025
Kriegstein
Gord Fishell
Flora Vaccarino
Zoltán Molnár

On 17 September 2024, 16:00, Professor Alan P. Koretsky, National Institutes of Health shall talk about MRI OF BRAIN PLASTICITY in Sherrington Library,
https://talks.ox.ac.uk/talks/id/77ce5625-6e62-4ced-8e14-02983c36097e/

Paper by Chrysa, Ellie and Anna that described a new form of plasticity when layer 5 driver input takes over the innervation of an originally first-order thalamic nucleus after early sensory deficit is doing well (in downloads) at Journal of Comparative Neurology https://doi.org/10.1002/cne.25304

Please hold the date for the next CORTICAL DEVELOPMENT MEETING in Giardini Naxos, Sicily, Italy - May 25-28, 2025

Dr Balázs V Varga of Cambridge Stem Cell Institute, University of Cambridge will deliver a talk: Capturing functional stem and immune cell states in early cortical development.

This will be held at 16.00 on Tuesday 6 August in the Sherrington Library

Generation of cortical neurons from endogenous progenitor cells is limited to prenatal development. In the human brain the process starts in the first trimester and the new neurons integrate in the developing neuronal networks early on. Disturbance of this early developmental process is indicated to result in neuronal network dysfunction manifesting as psychiatric conditions later in life. Studying how these processes are regulated and what cells are involved would help us understand how new cortical neurons can be generated and how the establishment of new synaptic connections can be facilitated. In my talk I am going to present our findings on the regulation of self-renewing cortical neural stem cells and the capture of a novel immune cell state involved in the establishment of active synapses between cortical neurons.

Florina presented a poster on her work on "Chronic abolition of evoked vesicle release from layer 5 projection neurons disrupts the laminar distribution of parvalbumin interneurons in the adult cortex" at the Summer Meeting of the Anatomical Society at Edinburgh. Preprint: https://doi.org/10.1101/2024.05.06.592829

NIH Oxford - Cambridge Scholars Program meeting today.

Oxford Autumn School in Neuroscience 2024
To be held on Monday 7th and Tuesday 8th October, Goss Lecture Theatre, Medical Sciences Teaching Centre, South Parks Road, Oxford. OX1 3PL

Featuring these sessions:

Brain Development - Chair: Professor Zoltán Molnár
Anxiety – Chair: Assoc. Professor Polly Waite
Frontal Lobe Interactions – Chair: Professor Matthew Rushworth
Dementia – Chair: Professor Masud Husian

See Detailed Programme and Register (general admission is free): https://www.tickettailor.com/events/oxfordneuroscience/1305040

2024 Sherrington Road Street Party - , The Department of Biochemistry, University of Oxford, INsD

Where Do Core Thalamocortical Axons Terminate in Mammalian Neocortex When There Is No Cytoarchitecturally Distinct Layer 4?
Although the mammalian cerebral cortex is most often described as a hexalaminar structure, there are cortical areas (primary motor cortex) and species (elephants, cetaceans, and hippopotami), where a cytoarchitecturally indistinct, or absent, layer 4 is noted.
We explored the termination sites of core thalamocortical projections in cortical areas and in species where there is no cytoarchitecturally distinct layer 4 using the immunolocalization of vesicular glutamate transporter 2, a known marker of core thalamocortical axon terminals, in 31 mammal species spanning the eutherian radiation.
We specifically examined regions of the cerebral cortex from various eutherian mammals that could be classified as (1) typical, in that they possessed six cortical layers with a cytoarchitecturally distinct layer 4 that presented with no sublamination (e.g., occipital cortex); (2) specialized, in that the cytoarchitecturally distinct layer 4 was sublaminated (e.g., primate primary visual cortex); and (3) atypical, in that they lacked a cytoarchitecturally distinct layer 4 (e.g., primate primary motor cortex, and occipital and temporal cortices in elephant, cetaceans, and hippopotamus). Six different patterns of core thalamic inputs to the cerebral cortex were observed across the species studies.
See paper by Bhagwandin et al., in Journal of Comparative Neurology: https://doi.org/10.1002/cne.25652

Huge congratulations!

Congratulations to the President, installed today as a member of the Order of the Thistle in Edinburgh. Visitors to St John's College, Oxford can celebrate too: visit our newly planted Scottish border (the College gardens are open daily from 1.00 to 5.00 pm or until dusk in winter)! https://bit.ly/4co6j9N

Learned a lot from examining Raquel Martínez-Serra's thesis on "Investigating multi-spine boutons in Alzheimer's disease" with Professor Tom Gillingwater (Edinburgh) yesterday at Department, Basic & Clinical Neuroscience at King's (https://www.kcl.ac.uk/neuroscience/about/departments/basic-clinical-neuroscience). Raquel was supervised by Professor Karl Peter Giese and Professor Lei Cho.

Today!

The current Library exhibition celebrates the founder of neurology, Thomas Willis (1621–75), who received his Bachelor of Medicine in Oxford during the Civil War. Willis was born into the time of the Scientific Revolution, the emergence of modern science in Europe. A co-founder of the Royal Society, Willis contributed to the emergence of 'science' in his field of Medicine by extracting knowledge from observation and experiments.Today, the circular arteries that supply blood to the brain are still known as the Circle of Willis. He also coined a considerable number of other neuroanatomical terms still in use and was the first to recognise a substantial number of pathologies.

The exhibition showcases first and early editions of his publications, his shorter-lived legacy in Chemistry, and his compassion as a practical physician in surviving letters to a colleague.

The exhibition can be visited until 29 August 2024. Members of College can visit the exhibition in the Library & Study Centre during opening hours (daily 9am – 11pm) at their convenience. Visitors who would like to view the exhibition are asked to email [email protected] to arrange an appointment. An online version of the exhibition is available here.
https://stjohnscollegelibraryoxford.org/2024/05/13/thomas-willis-1621-1675-neurologist-chemist-physician/
https://stjohnscollegelibraryoxford.org/2021/09/08/thomas-willis-1621-1675/
More literature:
https://doi.org/10.1038/nrn1369
https://doi.org/10.1093/brain/awab016

Cell numbers vary according to gyral, linear, or sulcal regions in the macaque cortex, but there is a consistent correlation between the number of white matter interstitial neutrons and the layer 5 and 6a neurons on all regions studied. https://doi.org/10.1002/cne.25626
Change in density and distribution of interstitial neurons has been observed in schizophrenia and epilepsy (Akbarian et al., 1996; Anderson et al., 1996; Eastwood & Harrison, 2003; Fung et al., 2014; Kirkpatrick et al., 1999, 2003 ; Meencke, 1983; Richter et al., 2016). It will require further studies to explore whether the altered distribution and cell numbers of WMICs that is observed in these conditions may be associated with alterations in respective cell numbers in layers 5 and 6a and whether the modifications in neuronal numbers are causally related.
Bashir Ahmed performed the entire study on archived material that is based on publicly available materials in Collection 6 of the MacBrain Resource Center hosted in the Department of Neuroscience at Yale University School of Medicine (https://medicine.yale.edu/neuroscience/macbrain/; Director Dr Alvaro Duque). Yale University

ANTHONY-S LaMANTIA: Polygenic Regulation of Cortical Circuit Development in Neurodevelopmental Disorders: Insights from a “Model” Copy Number Variant - https://talks.ox.ac.uk/talks/id/1e1bd1bf-fd4a-4a55-b18d-89faae7d1317/