Select cognitive deficits in vasoactive intestinal peptide deficient mice
Open accessAbstract
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. Conclusion: 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.
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Mice deficient in Vipr2 exhibit cognitive deficits associated with hippocampal dependent associative memory, which is reminiscent of schizophrenia.
“Mice that are deficient in Vipr2 exhibit cognitive deficits associate with hippocampal dependent associative memory- which is reminiscent of SZ172.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [172]
The Results section reports impaired recall of contextual fear conditioning in VIP-deficient mice at 48 and 72 hours. But the Discussion specifies that these mice lack the gene coding for VIP, not Vipr2, and the paper does not describe their deficits as reminiscent of schizophrenia. (LLM, conf=0.88)
Experimental — accuracy not yet measuredVIPR2 has several important roles in regulating neurodevelopment and behavior.
“VIPR2 has several important roles in regulating neurodevelopment and behavior (Chaudhury et al., 2008; Harmar et al., 2002; Waschek, 1995).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Chaudhury et al., 2008
VIP-deficient mice exhibit lower levels of recall, but retain circadian rhythms of recall, even in the absence of circadian rhythms in wheel running behavior.
“Although the VIP-deficient mice exhibit lower levels of recall, they retain circadian rhythms of recall, even in the absence of circadian rhythms in wheel running behavior.”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Chaudhury et al., 2008
Rhythms in recall in VIP-deficient mice are likely caused by circadian oscillations in some brain region other than the suprachiasmatic nucleus, perhaps the hippocampus.
“These rhythms in recall are likely to be caused by circadian oscillations in some brain region other than the SCN, perhaps the hippocampus, in view of its well known role in memory processes and its circadian expression of Per2 in VIP-deficient, behaviorally arrhythmic, mice (Chaudhury et al., 2008).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Chaudhury et al., 2008
Three treatments that disrupt circadian rhythms-mutation of the Period2 gene, mutation of the gene encoding VIP, and exposure to rapidly changing photoperiods-lead to deficits in fear conditioning recall in the absence of any detectable changes in acquisition of fear conditioning.
“Three treatments that disrupt circadian rhythms, i.e., mutation of the Period2 (Per2) gene, mutation of the gene encoding VIP, and exposure to rapidly changing photoperiods lead to deficits in fear conditioning recall in the absence of any detectable changes in acquisition of fear conditioning (Chaudhury et al., 2008).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Chaudhury et al., 2008
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- Authors
- Chaudhury, D., Loh, D. H., Dragich, J. M., Hagopian, A., & Colwell, C. S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Colwell, Christopher S
- Venue
- BMC Neuroscience
- Published
- 2008-07-10
- Volume
- 9
- Issue
- 1
- Pages
- 63-63
- ISSN
- 1471-2202 (ISSN-L)
- PMC
- PMC2474849
- OpenAlex
- W2156183803
- Cited by
- 73
- References
- 59
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 8 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 7 · 2013: 4 · 2012: 5
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- China Scholarship Council
- National Institutes of Health (T32 NS, NIH T32)
- University of California, Los Angeles
- National Heart, Lung, and Blood Institute (R21HL084240, HL84240)
- National Institute of Neurological Disorders and Stroke (T32 NS-07101-27, T32NS007101)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- vasoactive intestinal peptide, contextual fear conditioning, circadian rhythm, hippocampus, corticosterone, freezing behavior, learning and memory, neuropeptides
- MeSH terms
- Animals, Behavior, Animal, Brain, Circadian Rhythm, Cognition, Corticosterone, Hippocampus, Learning, Memory, Memory, Short-Term, Mice, Inbred C57BL, Motor Activity, Synaptic Transmission, Nuclear Proteins, RNA, Messenger, Suprachiasmatic Nucleus, Transcription Factors, Vasoactive Intestinal Peptide, In Situ Hybridization, Mice, Knockout, Cell Cycle Proteins, Receptors, Vasoactive Intestinal Peptide, Type II, Mice, Period Circadian Proteins
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