title: Knockdown of corticotropin-releasing factor 1 receptors in the ventral tegmental area enhances conditioned fear.
abstract: The neuropeptide corticotropin-releasing factor (CRF) coordinates the physiological and behavioural responses to stress. CRF receptors are highly expressed in the ventral tegmental area (VTA), an important region for motivated behaviour. Therefore, we examined the role of CRF receptor type 1 (CRFR1) in the VTA in conditioned fear, using a viral-mediated RNA interference approach. Following stereotaxic injection of a lentivirus that contained either shCRF-R1 or a control sequence, mice received tone-footshock pairings. Intra-VTA shCRF-R1 did not affect tone-elicited freezing during conditioning. Once conditioned fear was acquired, however, shCRF-R1 mice consistently showed stronger freezing to the tone even after extinction and reinstatement. These results implicate a novel role of VTA CRF-R1 in conditioned fear, and suggest how stress may modulate aversive learning and memory.
authors.affiliation: Behavioural Neuroscience Division, Florey Institute of Neuroscience & Mental Health, Parkville, VIC 3052 Australia; The Florey Department of Neuroscience & Mental Health, Australia.
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Chen
authors.affiliation: Behavioural Neuroscience Division, Florey Institute of Neuroscience & Mental Health, Parkville, VIC 3052 Australia; The Florey Department of Neuroscience & Mental Health, Australia.
authors.forename: Despina E
authors.initials: DE
authors.lastname: Ganella
authors.affiliation: Behavioural Neuroscience Division, Florey Institute of Neuroscience & Mental Health, Parkville, VIC 3052 Australia; The Florey Department of Neuroscience & Mental Health, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, VIC 3010 Australia.
authors.forename: Ross A D
authors.initials: RAD
authors.lastname: Bathgate
authors.affiliation: Department of stress Neurobiology and Neurogenetics, Max-Planck Institute of Psychiatry, Munich 80804, Germany.
authors.forename: Alon
authors.initials: A
authors.lastname: Chen
authors.affiliation: Behavioural Neuroscience Division, Florey Institute of Neuroscience & Mental Health, Parkville, VIC 3052 Australia; The Florey Department of Neuroscience & Mental Health, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.affiliation: Behavioural Neuroscience Division, Florey Institute of Neuroscience & Mental Health, Parkville, VIC 3052 Australia; The Florey Department of Neuroscience & Mental Health, Australia. Electronic address: drjeehyunkim@gmail.com.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001307:Auditory Perception / Q000502:physiology; D001362:Avoidance Learning / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology*; D004597:Electroshock; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics; D008297:Male; D008568:Memory / Q000502:physiology; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D018019:Receptors, Corticotropin-Releasing Hormone / Q000172:deficiency* / Q000235:genetics; D017557:Ventral Tegmental Area / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1
keywords: CRF; Fear; Memory; Stress; VTA