Matthew Grubb
King’s college – London, UK
Website
Venue: Centre Broca
Title
Functional recovery and plasticity during naturally occurring neuronal regeneration
Abstract
Attempts to repair the damaged or diseased brain have focused on facilitating the regrowth of existing axons, or introducing new neurons to replace lost projections. To achieve functional recovery, however, this is not enough – new projections must not only reach their intended target structures, but also re-connect appropriately to drive information processing in downstream circuits. How regrown or replaced axons can be encouraged to establish such appropriate connections, though, remains unknown. To understand some of the processes underlying successful re-connection of regenerated axons, we seek to learn lessons from part of the adult mammalian nervous system that can regenerate naturally – the projection from olfactory sensory neurons (OSNs) in the nose to their target structure in the brain, the olfactory bulb (OB). Using a simple model of olfactotoxin-induced OSN degeneration and subsequent naturally occurring regeneration, we study the anatomical and physiological properties of OSN axon terminals as they begin to re-connect with target circuits after a couple of weeks. We find that release probability is lower in immature re-connecting versus mature, fully-connected OSN terminals, and that even at the earliest stages of synapse re-establishment there is the potential for characteristic, strong presynaptic inhibition. However, despite immature OSN terminals being lower in density and functionally weaker, OSN-stimulated OB output is actually stronger in the earliest stages of re-connection. We are currently investigating the plastic mechanisms in OB circuits which enable such compensatory changes to occur, and hope that our discoveries will inform interventions to improve functional recovery after damage to the human CNS.
Primary research papers
Galliano E, Hahn C, Browne L, Rodriguez Villamayor P, Grubb MS (2020) Brief sensory deprivation triggers cell type-specific structural and functional plasticity in olfactory bulb neurons. bioRxiv 2020.05.10.086926. Free full text.
Byrne DJ, Lipovsek M, Grubb MS (2020) Brief sensory deprivation triggers plasticity of neurotransmitter-synthesising enzyme expression in genetically labelled olfactory bulb dopaminergic neurons. bioRxiv 2020.06.03.132555. Free full text.
Brann D, Tsukahara T, Weinreb C, Lipovsek M, Van den Berge K, Gong B, Chance R, Macaulay IC, Chou H-J, Fletcher R, Das D, Street K, Roux de Bezieux H, Choi Y-G, Risso D, Dudoit S, Purdom E, Mill JS, Hachem RA, Matsunami H, Logan DW, Goldstein B, Grubb MS, Ngai J, Datta SR (2020). Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Science Advances 6:eabc5801. Free full text. Raw data.
Galliano E, Franzoni E, Breton M, Chand AN, Byrne DJ, Murthy VN, Grubb MS (2018) Embryonic and postnatal neurogenesis produce functionally distinct subclasses of dopaminergic neuron. eLife, 7:e32373. Free full text. Raw data.
Evans MD, Tufo C, Dumitrescu AS, Grubb MS (2017) Myosin II activity is required for structural plasticity at the axon initial segment. Eur J Neurosci, 46: 1751. Free full text. Raw data. Featured article.
Dumitrescu AS, Evans MD, Grubb MS (2016) Evaluating tools for live imaging of structural plasticity at the axon initial segment. Front Cell Neurosci, 10: 268. Free full text.
Evans MD*, Dumitrescu AS*, Kruijssen Kruijssen DLH, Taylor SE, Grubb MS (2015) Rapid modulation of axon initial segment length influences repetitive spike firing. Cell Rep., 13:1233-45. Pubmed. Free full text.
Hannon E, Chand AN, Evans MD, Wong CCY, Grubb MS*, Mill J* (2015) A role for CaV1 and calcineurin signalling in depolarization-induced changes in neuronal DNA methylation. Neuroepigenetics 2015 Jun 25; 3:1-6. Pubmed. Free full text.
Chand AN, Galliano E, Chesters RA, Grubb MS (2015) A distinct subtype of dopaminergic interneuron displays inverted structural plasticity at the axon initial segment. J. Neurosci 2015 Jan 28;35(4):1573-90. Pubmed. Free full text.
Evans MD, Sammons RP, Lebron S, Dumitrescu AS, Watkins TBK, Uebele VN, Renger JJ, Grubb MS (2013) Calcineurin Signaling Mediates Activity-Dependent Relocation of the Axon Initial Segment. J. Neurosci Apr 17;33(16):6950-63. Pubmed. Free full text [Adobe Acrobat PDF – 3.84 MB]
Organized by Bordeaux Neurocampus, NBA and Bordeaux Neurocampus Graduate Program