BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:From the whole CNS to defined brain nuclei to neurotransmitter cel
 l type-specific circuits: Using mouse genetics to dissect CRF-dependent me
 chanisms driving stress-induced emotional behaviour - Dr Damian Refojo\, M
 olecular Neurobiology Research Group\, Max Planck Institute of Psychiatry\
 , Munich.
DTSTART:20101117T163000Z
DTEND:20101117T173000Z
UID:TALK26457@talks.cam.ac.uk
CONTACT:Suzy Blows
DESCRIPTION:Corticotropin-releasing factor (CRF) is a neuropeptide widely 
 distributed throughout the CNS where it acts as a neuromodulator orchestra
 ting adaptive responses to stress such as anxiety\, locomotor activity\, f
 ear response\, and neuroendocrine regulation. Impairments in the physiolog
 ical CRF responses to stress are substantially involved in the causation a
 nd development of mood disorders such as depression and anxiety. Therefore
 \, there is an urgent need to understand the brain areas involved\, activa
 ted neurotransmitter circuits and molecular mechanisms underlying the effe
 cts of CRF/CRF-R1 on emotional behaviour.\n\nAs neuroregulator\, CRF does 
 not have neurotransmitter effects per se but its function rely on the modu
 lation of true neurotransmitter systems. Which neurotransmitter circuits a
 re involved in modulating CRF-R1-dependent behaviours is a fundamental que
 stion in the biology of stress and stress-related disorders. In order to d
 issect the neurotransmitter identity of neurons expressing CRF-R1\, we map
 ped CRF-R1 expression throughout the brain using double labelling histoche
 mical approaches and by means of a newly developed CRF-R1-EGFP reporter mo
 use line. \n\nUsing genetically engineered mice\, we have shown that conve
 ntional CRF1 knock-out (KO) and limbic-specific CRF-R1-CamKII conditional 
 KO mice display reduced anxiety-like behaviour. Nevertheless the cellular 
 identity of telencephalic circuits controlling anxiety via CRF and the put
 ative contribution of other brainstem-located neurotransmitter systems rem
 ain unclear. To address this question we used a conditional mutagenesis ap
 proach based on the Cre/loxP system to dissect the precise contribution of
  CRF-R1 on different neuronal populations in living animals. We crossed CR
 F-R1flox/flox mice with neurotransmitter-cell type specific Cre lines to s
 pecifically ablate CRF-R1 only in glutamatergic\, GABAergic\, dopaminergic
  and serotonergic neurons of the brain. \nA comprehensive series of studie
 s were performed in every mutant mouse line including behavioural phenotyp
 ing\, neuroendocrine response\, expression profiling\, neurotransmitter re
 lease\, and electrophysiological analysis. The specific contribution of CR
 F-R1 in each neurotransmitter system on different aspects of the stress re
 sponse and its putative role in affective disorders will be discussed.
LOCATION:Lecture Theatre 1\, Department of Veterinary Medicine
END:VEVENT
END:VCALENDAR