Altered Neural Excitability and Chronic Anxiety in a Mouse Model of Fragile X

With a $35,000 bridge grant from FRAXA Research Foundation, Dr. Peter Vanderklish and colleagues explored the basis of anxiety in fragile X syndrome in a mouse model of the disorder. His focus is an area of the brain, BNST.

Peter Vanderklish
$35,000 Grant
Peter Vanderklish, PhD
Principal Investigator
Walter Francesconi, PhD
Co-Principal Investigator
Julie Lauterborn, PhD
Co-Principal Investigator
Scripps Research Institute
2016 FRAXA Research Grant
$35,000

Altered neural excitability in the BNST as a basis of, and therapeutic target for, chronic emotional symptoms in fragile X syndrome

Long-term anxiety and fear states are mediated by the brain’s bed nucleus of the stria terminalis (BNST), a hub for modulation of anxiety and stress responses. We have found evidence in fragile X mice that suggests a state of chronically reduced anxiolytic drive of BNST by insula and other inputs. This suggests a state at baseline that is analogous to the effects of long-term stress on BNST in normal individuals. We propose further that these changes involve insula-BNST pathways underlying social anxiety and aversion.

Our objectives are to test this hypotheses and the efficacy of HSD11[beta]1 inhibitors on BNST function and anxiety behaviors in fragile X model mice.

Previous Grants to this Team

Therapeutic Targeting of the AMP-Activated Protein Kinase Pathway in Fragile X
$100,000 in 2015

Since 2003 when Dr. Vanderklish attended a Fragile X Banbury meeting, he has been studying neurons from the Fragile X knockout mouse. He has applied a variety of biochemical, proteomic, and electrophysiological methods to elucidate dysfuntions in synaptic function that may contribute to Fragile X syndrome, and to identify new strategies for pharmacological therapy.

$40,000 in 2008
$50,000 in 2007
$80,000 in 2006
$50,000 in 2005
$95,000 in 2004