Haploinsufficiency of the arginine–vasopressin gene is associated with poor spatial working memory performance in rats

Aarde, Shawn M.; Jentsch, J. David

doi:10.1016/j.yhbeh.2005.11.002

Cited by 29 publications

(24 citation statements)

References 60 publications

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“…Combined, the above studies indicate a general beneficial effect of Avp administration on spatial memory. Endogenous Avp is likely necessary for spatial memory performance, as animals with partial vasopressin insufficiency (Brattleboro heterozygotes: +/di) demonstrate poorer working memory than wildtype controls on a delayednon-match-to-sample task in which the animal has to respond to an illuminated aperture different from the one on which it had been trained (Aarde and Jentsch, 2006). Not all studies agree on the effect within the brain of Avp or its fragments on spatial memory.…”

Section: Spatial Learningmentioning

confidence: 99%

Vasopressin: Behavioral roles of an “original” neuropeptide

Caldwell

Lee

Macbeth

et al. 2008

Progress in Neurobiology

427

416

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Vasopressin (Avp) is mainly synthesized in the magnocellular cells of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) whose axons project to the posterior pituitary. Avp is then released into the blood stream upon appropriate stimulation (e.g., hemorrhage or dehydration) to act at the kidneys and blood vessels. The brain also contains several populations of smaller, parvocellular neurons whose projections remain within the brain. These populations are located within the PVN, bed nucleus of the stria terminalis (BNST), medial amygdala (MeA) and suprachiasmatic nucleus (SCN).Since the 1950's, research examining the roles of Avp in the brain and periphery has intensified. The development of specific agonists and antagonists for Avp receptors has allowed for a better elucidation of its contributions to physiology and behavior. Anatomical, pharmacological and transgenic, including "knockout," animal studies, have implicated Avp in the regulation of various social behaviors across species.Avp plays a prominent role in the regulation of aggression, generally of facilitating or promoting it. Affiliation and certain aspects of pair-bonding are also influenced by Avp. Memory, one of the first brain functions of Avp that was investigated, has been implicated especially strongly in social recognition. The roles of Avp in stress, anxiety, and depressive states are areas of active exploration. In this review, we concentrate on the scientific progress that has been made on understanding the role of Avp in regulating of these and other behaviors across species, as well as discuss the implications for human behavior.

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Section: Spatial Learningmentioning

confidence: 99%

Vasopressin: Behavioral roles of an “original” neuropeptide

Caldwell

Lee

Macbeth

et al. 2008

Progress in Neurobiology

427

416

View full text Add to dashboard Cite

show abstract

“…A recent study showed that oxytocin, a neuropeptide involved in social bonding, increased interpersonal synchronization in a tapping task [58]. Because also vasopressin has strong connections with sociality [59], spatial and social memory [60,61], as well as with higher cognitive functions such as memory and learning in humans and other mammals [62], a series of studies started to investigate the role of vasopressin also in human music and dance. Such a coalition has been reported in several studies: the gene responsible for vasopressin receptor, AVPR1a, was associated with the dance phenotype [63], musical short-term memory [64], musical skills [65], and lifelong active listening to music [66].…”

Section: Vasopressin Courtship and Musicmentioning

confidence: 99%

Sexual arousal and rhythmic synchronization: A possible effect of vasopressin

Miani

2016

Medical Hypotheses

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“…To specifically address working memory function in Nf1 +/− mice, we tested performance on an operant spatial delayed nonmatch to sample task (29)(30)(31). In this task, mice are given serial trials, each consisting of two phases (sample presentation and choice) separated by a variable delay of 3-10 s. Both Nf1 +/− and WT mice showed comparable ability to accurately respond to the cue presented in the sample phase, indicating that sensorimotor function, motivation, and response selection were normal in Nf1 +/− mice.…”

Section: Nf1mentioning

confidence: 99%

Neurofibromin regulates corticostriatal inhibitory networks during working memory performance

Shilyansky

Karlsgodt

Cummings

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

150

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Neurofibromatosis type I (NF1) is one of the most common singlegene causes of learning disabilities. Here, we use behavioral working memory probes and electrophysiological studies in a mouse model of NF1 (Nf1 heterozygous null mutants; Nf1 +/− ) to demonstrate that (i) Neurofibromin regulates prefrontal and striatal inhibitory networks, specifically activity-dependent GABA release and (ii) is required for working memory performance, with inhibitiondependent working memory deficits seen in Nf1 +/− mice. We find that increased inhibition in medial prefrontal cortex (mPFC) is sufficient to alter persistent activity in a biophysical model of an mPFC microcircuit, suggesting a possible mechanism for Nf1 +/− working memory deficits. Accordingly, working memory assays applied during functional MRI (fMRI) studies in human subjects with NF1 reveal hypoactivation of corticostriatal networks, which is associated with impaired working memory performance. Collectively, these integrative mouse and human studies reveal molecular and cellular mechanisms contributing to working memory deficits in NF1.GABA | Ras | prefrontal cortex | learning disability | neurofibromatosis type I N eurofibromatosis type 1 (NF1) is a valuable model for understanding mechanisms of learning disabilities (1). NF1 is a common genetic disorder (incidence 1:3,000) that results from mutations in a single gene (Nf1) that encodes the neurofibromin protein (2, 3). Specific deficits in the domains of visuospatial and executive functions are among the most common cognitive deficits associated with this syndrome (1,4,5). Previous mechanistic studies in a mouse model of NF1 (Nf1 heterozygous null mutants or Nf1 +/− ) demonstrated that neurofibromin modulates Rasdependent GABA release in the hippocampus, which in turn modulates long-term potentiation (LTP) and hippocampaldependent learning (6, 7). However, the mechanisms underlying frontal executive dysfunction in NF1, including prominent working memory deficits (5), are unknown. Therefore, to investigate mechanisms underlying working memory deficits associated with the NF1 mutation we carried out parallel experiments in mice and humans.Working memory is a cognitive construct involving the ability to hold and update information transiently in mind in the service of higher-order cognitive activities. Executive functions, including working memory, are thought to depend on common corticostriatal networks (8-11). Therefore, our experiments focused on frontal corticostriatal circuitry, with an emphasis on the dorsolateral prefrontal cortex (DLPFC) in humans, thought to be critical for working memory (12), and its functionally analogous structure in rodents, the medial prefrontal cortex (mPFC) (13,14).Here, we report Ras-dependent increases in GABA release in the mPFC and striatum of the Nf1 +/− mouse model. Increased GABAergic inhibition is likely to be responsible for the working memory deficits that we found in the Nf1 +/− mice because these deficits could be reversed with a drug that decreased inhibition. Further,...

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Haploinsufficiency of the arginine–vasopressin gene is associated with poor spatial working memory performance in rats

Cited by 29 publications

References 60 publications

Vasopressin: Behavioral roles of an “original” neuropeptide

Vasopressin: Behavioral roles of an “original” neuropeptide

Sexual arousal and rhythmic synchronization: A possible effect of vasopressin

Neurofibromin regulates corticostriatal inhibitory networks during working memory performance

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