Select cognitive deficits in vasoactive intestinal peptide deficient mice.
BACKGROUND
The neuropeptide vasoactive intestinal peptide (VIP) is widely distributed in the adult central nervous system where this peptide functions to regulate synaptic transmission and neural excitability. The expression of VIP and its receptors in brain regions implicated in learning and memory functions, including the hippocampus, cortex, and amygdala, raise the possibility that this peptide may function to modulate learned behaviors. Among other actions, the loss of VIP has a profound effect on circadian timing and may specifically influence the temporal regulation of learning and memory functions.


RESULTS
In the present study, we utilized transgenic VIP-deficient mice and the contextual fear conditioning paradigm to explore the impact of the loss of this peptide on a learned behavior. We found that VIP-deficient mice exhibited normal shock-evoked freezing behavior and increases in corticosterone. Similarly, these mutant mice exhibited no deficits in the acquisition or recall of the fear-conditioned behavior when tested 24-hours after training. The VIP-deficient mice exhibited a significant reduction in recall when tested 48-hours or longer after training. Surprisingly, we found that the VIP-deficient mice continued to express circadian rhythms in the recall of the training even in those individual mice whose wheel running wheel activity was arrhythmic. One mechanistic explanation is suggested by the finding that daily rhythms in the expression of the clock gene Period2 continue in the hippocampus of VIP-deficient mice.


CONCLUSIONS
Together these data suggest that the neuropeptide VIP regulates the recall of at least one learned behavior but does not impact the circadian regulation of this behavior.
Chaudhury
Dipesh
D
Department of Psychiatry and Biobehavioral Sciences, University of California - Los Angeles, 760 Westwood Plaza, Los Angeles, California 90024-1759, USA. dc478@cornell.edu
Loh
Dawn H
DH
Dragich
Joanna M
JM
Hagopian
Arkady
A
Colwell
Christopher S
CS
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D017403:In Situ Hybridization; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014157:Transcription Factors; C495510:Vipr2 protein, mouse; D014660:Vasoactive Intestinal Peptide; D003345:Corticosterone