Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain

  1. Justyna Pielecka-Fortuna  Is a corresponding author
  2. Evgenia Kalogeraki
  3. Michal G Fortuna
  4. Siegrid Löwel
  1. University of Göttingen, Germany
  2. German Primate Center, Germany

Abstract

The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMPs-activation, we examined the effects of MMPs-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMPs-inhibitor prevented visual plasticity. Additionally, treatment with MMPs-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that a fine balance of MMPs-activity is crucial for adult visual plasticity to occur.

Article and author information

Author details

  1. Justyna Pielecka-Fortuna

    Department of Systems Neuroscience, Bernstein Focus Neurotechnology, Johann-Friedrich-Blumenbach Institute for Zoology and Anthropology, University of Göttingen, Göttingen, Germany
    For correspondence
    jpielec@gwdg.de
    Competing interests
    The authors declare that no competing interests exist.
  2. Evgenia Kalogeraki

    Göttingen Graduate School for Neurosciences, Biophysics, and Molecular Biosciences, University of Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Michal G Fortuna

    German Primate Center, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Siegrid Löwel

    Department of Systems Neuroscience, Bernstein Focus Neurotechnology, Johann-Friedrich-Blumenbach Institute for Zoology and Anthropology, University of Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experimental procedures were approved by the local government (Niedersächsisches Landesamt für Verbraucherschutz und Lebensmittelsicherheit, registration number 33.9-42502-04-10/0326). All surgeries were performed under isoflurane or halothane anesthesia and every effort was made to minimize suffering.

Copyright

© 2015, Pielecka-Fortuna et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,417
    views
  • 230
    downloads
  • 12
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Justyna Pielecka-Fortuna
  2. Evgenia Kalogeraki
  3. Michal G Fortuna
  4. Siegrid Löwel
(2015)
Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain
eLife 4:e11290.
https://doi.org/10.7554/eLife.11290

Share this article

https://doi.org/10.7554/eLife.11290

Further reading

    1. Neuroscience
    Samyogita Hardikar, Bronte Mckeown ... Jonathan Smallwood
    Research Article

    Complex macro-scale patterns of brain activity that emerge during periods of wakeful rest provide insight into the organisation of neural function, how these differentiate individuals based on their traits, and the neural basis of different types of self-generated thoughts. Although brain activity during wakeful rest is valuable for understanding important features of human cognition, its unconstrained nature makes it difficult to disentangle neural features related to personality traits from those related to the thoughts occurring at rest. Our study builds on recent perspectives from work on ongoing conscious thought that highlight the interactions between three brain networks – ventral and dorsal attention networks, as well as the default mode network. We combined measures of personality with state-of-the-art indices of ongoing thoughts at rest and brain imaging analysis and explored whether this ‘tri-partite’ view can provide a framework within which to understand the contribution of states and traits to observed patterns of neural activity at rest. To capture macro-scale relationships between different brain systems, we calculated cortical gradients to describe brain organisation in a low-dimensional space. Our analysis established that for more introverted individuals, regions of the ventral attention network were functionally more aligned to regions of the somatomotor system and the default mode network. At the same time, a pattern of detailed self-generated thought was associated with a decoupling of regions of dorsal attention from regions in the default mode network. Our study, therefore, establishes that interactions between attention systems and the default mode network are important influences on ongoing thought at rest and highlights the value of integrating contemporary perspectives on conscious experience when understanding patterns of brain activity at rest.

    1. Neuroscience
    John P Grogan, Matthias Raemaekers ... Sanjay G Manohar
    Research Article

    Motivation depends on dopamine, but might be modulated by acetylcholine which influences dopamine release in the striatum, and amplifies motivation in animal studies. A corresponding effect in humans would be important clinically, since anticholinergic drugs are frequently used in Parkinson’s disease, a condition that can also disrupt motivation. Reward and dopamine make us more ready to respond, as indexed by reaction times (RT), and move faster, sometimes termed vigour. These effects may be controlled by preparatory processes that can be tracked using electroencephalography (EEG). We measured vigour in a placebo-controlled, double-blinded study of trihexyphenidyl (THP), a muscarinic antagonist, with an incentivised eye movement task and EEG. Participants responded faster and with greater vigour when incentives were high, but THP blunted these motivational effects, suggesting that muscarinic receptors facilitate invigoration by reward. Preparatory EEG build-up (contingent negative variation [CNV]) was strengthened by high incentives and by muscarinic blockade, although THP reduced the incentive effect. The amplitude of preparatory activity predicted both vigour and RT, although over distinct scalp regions; frontal activity predicted vigour, whereas a larger, earlier, central component predicted RT. The incentivisation of RT was partly mediated by the CNV, though vigour was not. Moreover, the CNV mediated the drug’s effect on dampening incentives, suggesting that muscarinic receptors underlie the motivational influence on this preparatory activity. Taken together, these findings show that a muscarinic blocker impairs motivated action in healthy people, and that medial frontal preparatory neural activity mediates this for RT.