Search anything and hit enter
  • Teams
  • Members
  • Projects
  • Events
  • Calls
  • Jobs
  • publications
  • Software
  • Tools
  • Network
  • Equipment

A little guide for advanced search:

  • Tip 1. You can use quotes "" to search for an exact expression.
    Example: "cell division"
  • Tip 2. You can use + symbol to restrict results containing all words.
    Example: +cell +stem
  • Tip 3. You can use + and - symbols to force inclusion or exclusion of specific words.
    Example: +cell -stem
e.g. searching for members in projects tagged cancer
Search for
Count
IN
OUT
Content 1
  • member
  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Full Professor
  • Graduate Student
  • Lab assistant
  • Non-permanent Researcher
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
Content 2
  • member
  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Full Professor
  • Graduate Student
  • Lab assistant
  • Non-permanent Researcher
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
Search
Go back
Scroll to top
Share
© Shalin E. Abraham, Michael Häusser, Christoph Schmidt-Hieber, University College London
The dentate gyrus is one of the few mammalian brain regions where new neurons are generated throughout life. The image was taken with a confocal microscope from a parasagittal slice of the mouse hippocampus. Cells were labelled with fluorescent markers: Newly generated neurons are red (doublecortin), mature neurons are green (NeuN), and nuclei are blue (DAPI)
Publication : The Journal of neuroscience : the official journal of the Society for Neuroscience

Protein Kinase A deregulation in the medial prefrontal cortex impairs working memory in murine Oligophrenin1 deficiency

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of neuroscience : the official journal of the Society for Neuroscience - 13 Oct 2017

Zhang CL, Aime M, Laheranne E, Houbaert X, El Oussini H, Martin C, Lepleux M, Normand E, Chelly J, Herzog E, Billuart P, Humeau Y

Link to Pubmed [PMID] – 29030432

J. Neurosci. 2017 Oct;

Classical and systems genetics have identified wide networks of genes associated with cognitive and neurodevelopmental diseases. In parallel to deciphering the role of each of these genes in neuronal or synaptic function, evaluating the response of neuronal and molecular networks to gene loss-of-function could reveal some pathophysiological mechanisms potentially accessible to non-genetic therapies. Loss of function of the Rho-GAP Oligophrenin-1 is associated with cognitive impairments in both human and mouse. Up-regulation of both PKA and ROCK has been reported in Ophn1(-/y) mice, but it remains unclear if kinase hyperactivity contributes to the behavioural phenotypes. In this study, we thoroughly characterized a prominent perseveration phenotype displayed by Ophn1 deficient mice using a Y-maze spatial working memory (SWM) test. We report that Ophn1 deficiency in the mouse generated severe cognitive impairments, characterized by both a high occurrence of perseverative behaviours and a lack of deliberation during SWM test. In vivo and in vitro pharmacological experiments suggest that PKA dysregulation in the mPFC underlies cognitive dysfunction in Ophn1 deficient mice, as assessed using a delayed spatial alternation task results. Functionally, mPFC neuronal networks appeared to be affected in a PKA-dependent manner, whereas hippocampal-PFC projections involved in SWM were not affected in Ophn1(-/y) mice. Thus, we propose that discrete gene mutations in intellectual disability might generate “secondary” pathophysiological mechanisms, which are prone to become pharmacological targets for curative strategies in adult patients.SIGNIFICANCE STATEMENTHere we report that Ophn1 deficiency generates severe impairments in performance at spatial working memory tests, characterized by a high occurrence of perseverative behaviours and a lack of decision making. This cognitive deficit is consecutive to PKA deregulation in the mPFC that prevents Ophn1 KO mice to exploit a correctly acquired rule. Functionally, mPFC neuronal networks appear to be affected in a PKA-dependent manner, whereas behaviourally important hippocampal projections were preserved by the mutation. Thus, we propose that discrete gene mutations in intellectual disability can generate “secondary” pathophysiological mechanisms prone to become pharmacological targets for curative strategies in adults.

https://www.ncbi.nlm.nih.gov/pubmed/29030432