VPAC receptor signaling modulates grouping behavior and social responses to contextual novelty in a gregarious finch: a role for a putative prefrontal cortex homologue

“…these brain areas ghts reserved. regulate social recognition, affiliation, grouping, aggression, appetitive and consummatory sexual behavior, parental behavior and responses to social stress (Goodson, 2005; Newman, 1999), and thus VIPmay play important roles in numerous aspects of social behavior.”

“It is important to consider that the effects of VPAC receptor antagonism, including the site-specific effects on gregariousness, may also be due to the contributions of PACAP and/or VIP, both of which can bind to VPAC receptors with equal affinity (Harmar et al., 2012; Vaudry et al., 2009).”

“…these brain areas ghts reserved. regulate social recognition, affiliation, grouping, aggression, appetitive and consummatory sexual behavior, parental behavior and responses to social stress (Goodson, 2005; Newman, 1999), and thus VIPmay play important roles in numerous aspects of social behavior.”

“The mammalian prefrontal cortex and nucleus accumbens are part of the mesolimbic dopaminergic reward pathway and are involved in the motivation and reinforcing effects of abusive drugs, as well as natural stimuli (McBride et al., 1999).”

“We additionally measured exploration of a novel environment, an anxiety assay widely used in birds (Biondi et al., 2010; Groothuis and Carere, 2005; Kelly et al., 2011; Martins et al., 2007).”

“Not surprisingly, these two key areas of the mesolimbic reward pathway are particularly important for affiliation and social attachment behavior, as demonstrated in prairie voles (Young et al., 2001).”

“It is important to consider that the effects of VPAC receptor antagonism, including the site-specific effects on gregariousness, may also be due to the contributions of PACAP and/or VIP, both of which can bind to VPAC receptors with equal affinity (Harmar et al., 2012; Vaudry et al., 2009).”

“Both the hippocampus and LS contain VIP receptors (Goodson et al., 2006), and the hippocampus contains a fairly large population of VIP neurons (Bottjer and Alexander, 1995; Erichsen et al., 1991; Luo et al., 2011).”

“anterior hypothalamus, AH, and ventromedial hypothalamus, VMH), VIP receptors, cells and/or fibers are also present in many other areas that comprise a social behavior network (Goodson, 2005; Newman, 1999), including the medial extended amygdala (medial amygdala and medial bed nucleus of the stria terminalis, BSTm), m…”

“…bed nucleus of the stria terminalis, BSTm), midbrain central gray, ventral tegmental area and lateral septum (LS) (Antonopoulos et al., 1987; Bottjer andAlexander, 1995; Hof et al., 1991; Joo et al., 2004; Kuenzel and Blahser, 1994; Kuenzel et al., 1997; Roberts et al., 1982; Sims et al., 1980).”

“Peptide circuits of the BSTmandLS are particularly important for grouping behavior and social affiliation in birds and mammals, although this has been primarily studied with regard to the nonapeptides (Curley et al., 2009, 2012; Goodson and Wang, 2006; Goodson et al., 2009a, 2009b, 2012a, 2012c; Kelly et al., 2011; Li…”

“Projections from the mediodorsal thalamus are a major defining feature of the mammalian prefrontal cortex (Divac et al., 1978; Kuroda et al., 1998),”

“…VIP-induced prolactin secretion is reduced by testosterone, apparently at the level of the pituitary (Knapp et al., 1988), suggesting a potential mechanism for the tradeoffs commonly observed between testosterone-mediated behaviors (e.g., aggression) and parental behavior (McGlothlin et al., 2007).”

“Furthermore, many of PACAP effects on social behavior, including anxiety, stress and affiliative behavior, appear to be mediated specifically via the PAC1 receptor (Hammack et al., 2009; Nicot et al., 2004; Otto et al., 2001).”

“…septum (an AH projection target; Atoji andWild, 2004) facilitate aggression in the context of territory defense, weakly reduce aggression in the context of mate competition (Goodson, 1998b; Goodson and Adkins-Regan, 1999), and inhibit territorial dawn song inmale field sparrows (Goodson, 1998a).”

“We additionally measured exploration of a novel environment, an anxiety assay widely used in birds (Biondi et al., 2010; Groothuis and Carere, 2005; Kelly et al., 2011; Martins et al., 2007).”

“Projections from the mediodorsal thalamus are a major defining feature of the mammalian prefrontal cortex (Divac et al., 1978; Kuroda et al., 1998),”

“anterior hypothalamus, AH, and ventromedial hypothalamus, VMH), VIP receptors, cells and/or fibers are also present in many other areas that comprise a social behavior network (Goodson, 2005; Newman, 1999), including the medial extended amygdala (medial amygdala and medial bed nucleus of the stria terminalis, BSTm), m…”

“Both the hippocampus and LS contain VIP receptors (Goodson et al., 2006), and the hippocampus contains a fairly large population of VIP neurons (Bottjer and Alexander, 1995; Erichsen et al., 1991; Luo et al., 2011).”

“…septum (an AH projection target; Atoji andWild, 2004) facilitate aggression in the context of territory defense, weakly reduce aggression in the context of mate competition (Goodson, 1998b; Goodson and Adkins-Regan, 1999), and inhibit territorial dawn song inmale field sparrows (Goodson, 1998a).”

“Novelty suppression of feeding tests are increasingly used as measures of anxiety (Bilkei-Gorzo et al., 2002; Catts et al., 2008; Greene et al., 2009; Leuner et al., 2010) and have been readily adapted to birds (Kelly et al., 2011).”

“…by numerous hypothalamic and extrahypothalamic cell groups and is perhaps best known for its role in the stimulation of prolactin release (Christensen and Vleck, 2008; Christian et al., 2007; El Halawani et al., 1996; Lam, 1991; Macnamee et al., 1986; Maney et al., 1999; Vleck and Patrick, 1999).”

“Novelty suppression of feeding tests are increasingly used as measures of anxiety (Bilkei-Gorzo et al., 2002; Catts et al., 2008; Greene et al., 2009; Leuner et al., 2010) and have been readily adapted to birds (Kelly et al., 2011).”

“Furthermore, many of PACAP effects on social behavior, including anxiety, stress and affiliative behavior, appear to be mediated specifically via the PAC1 receptor (Hammack et al., 2009; Nicot et al., 2004; Otto et al., 2001).”

“To further examine VIP’s role in anxiety, we performed two behavioral tests, novelty suppressed feeding and exploration of a novel environment on the fifth day of testing (day 9 overall), that have previously been used to measure general anxiety-like behavior in zebra finches (Kelly et al., 2011; Martins et al., 2007).”

“Novelty suppression of feeding tests are increasingly used as measures of anxiety (Bilkei-Gorzo et al., 2002; Catts et al., 2008; Greene et al., 2009; Leuner et al., 2010) and have been readily adapted to birds (Kelly et al., 2011).”

“…several studies implicate circuitry of the hippocampus and LS in reactions to novelty and exploration of novel environments, but without a social component (Belzung, 1992; Poucet, 1989; Trent and Menard, 2010), whereas our effects to contextual novelty were only observed in a social context.”

“This latter pattern in sparrows is also observed in the paraventricular nucleus of the hypothalamus (Goodson et al., 2012c), and thus the paraventricular nucleus may also be a site of action in the present experiments.”

“…septum (an AH projection target; Atoji andWild, 2004) facilitate aggression in the context of territory defense, weakly reduce aggression in the context of mate competition (Goodson, 1998b; Goodson and Adkins-Regan, 1999), and inhibit territorial dawn song inmale field sparrows (Goodson, 1998a).”

“…for grouping behavior and social affiliation in birds and mammals, although this has been primarily studied with regard to the nonapeptides (Curley et al., 2009, 2012; Goodson and Wang, 2006; Goodson et al., 2009a, 2009b, 2012a, 2012c; Kelly et al., 2011; Liu et al., 2001; Ophir et al., 2009).”

“Similarly, parallel changes in VIP cell size and prolactin levels are observed during the incubation and brooding stages in ring doves (Cheng and Burke, 1983; Cloues et al., 1990; Goldsmith et al., 1981).”

“…for grouping behavior and social affiliation in birds and mammals, although this has been primarily studied with regard to the nonapeptides (Curley et al., 2009, 2012; Goodson and Wang, 2006; Goodson et al., 2009a, 2009b, 2012a, 2012c; Kelly et al., 2011; Liu et al., 2001; Ophir et al., 2009).”

“VIP in turn modulates the secretion of gonadotropin-releasing hormone in rats (Christian and Moenter, 2008).”

“Given that 1) anatomical studies link VIP signaling to gregariousness in multiple species of birds (Goodson et al., 2006; Goodson et al., 2012c), 2) VIP manipulations significantly impact social behavior in mice and birds (Goodson et al.”

“…these two sites are extremely important for the regulation of grouping behavior and affiliation, particularly with respect to nonapeptide signaling (Curley et al., 2009, 2012; Goodson and Wang, 2006; Goodson et al., 2009a, 2009b, 2012a, 2012c; Kelly et al., 2011; Liu et al., 2001; Ophir et al.,…”

“Interestingly, the results of a recent anatomical study suggest that the medial pallium in pigeons (which includes the medial nidopallium, mesopallium and apical part of the hyperpallium; areas whichmake up our TEL category), is likely homologous to the mammalian prefrontal cortex, based on 1) the medial pallium's ext…”

“Novelty suppression of feeding tests are increasingly used as measures of anxiety (Bilkei-Gorzo et al., 2002; Catts et al., 2008; Greene et al., 2009; Leuner et al., 2010) and have been readily adapted to birds (Kelly et al., 2011).”

“Furthermore, many of PACAP effects on social behavior, including anxiety, stress and affiliative behavior, appear to be mediated specifically via the PAC1 receptor (Hammack et al., 2009; Nicot et al., 2004; Otto et al., 2001).”

“…several studies implicate circuitry of the hippocampus and LS in reactions to novelty and exploration of novel environments, but without a social component (Belzung, 1992; Poucet, 1989; Trent and Menard, 2010), whereas our effects to contextual novelty were only observed in a social context.”

“VIP is thought to be important for parental behavior, given that it is the primary prolactin releasing factor in birds (El Halawani et al., 1997) and prolactin secretion is particularly important for egg incubation in galliforms (El Halawani et al., 1984).”

“…two sites are extremely important for the regulation of grouping behavior and affiliation, particularly with respect to nonapeptide signaling (Curley et al., 2009, 2012; Goodson and Wang, 2006; Goodson et al., 2009a, 2009b, 2012a, 2012c; Kelly et al., 2011; Liu et al., 2001; Ophir et al., 2009).”

“…by numerous hypothalamic and extrahypothalamic cell groups and is perhaps best known for its role in the stimulation of prolactin release (Christensen and Vleck, 2008; Christian et al., 2007; El Halawani et al., 1996; Lam, 1991; Macnamee et al., 1986; Maney et al., 1999; Vleck and Patrick, 1999).”

“…by numerous hypothalamic and extrahypothalamic cell groups and is perhaps best known for its role in the stimulation of prolactin release (Christensen and Vleck, 2008; Christian et al., 2007; El Halawani et al., 1996; Lam, 1991; Macnamee et al., 1986; Maney et al., 1999; Vleck and Patrick, 1999).”

“…by numerous hypothalamic and extrahypothalamic cell groups and is perhaps best known for its role in the stimulation of prolactin release (Christensen and Vleck, 2008; Christian et al., 2007; El Halawani et al., 1996; Lam, 1991; Macnamee et al., 1986; Maney et al., 1999; Vleck and Patrick, 1999).”

“VIP innervation of the LS also varies between color morphs of the white-throated sparrow (Zonotrichia leucophrys) that differ in their levels of parental care and aggression (Maney et al., 2005).”

“This latter pattern in sparrows is also observed in the paraventricular nucleus of the hypothalamus (Goodson et al., 2012c), and thus the paraventricular nucleus may also be a site of action in the present experiments.”

“…several studies implicate circuitry of the hippocampus and LS in reactions to novelty and exploration of novel environments, but without a social component (Belzung, 1992; Poucet, 1989; Trent and Menard, 2010), whereas our effects to contextual novelty were only observed in a social context.”

“anterior hypothalamus, AH, and ventromedial hypothalamus, VMH), VIP receptors, cells and/or fibers are also present in many other areas that comprise a social behavior network (Goodson, 2005; Newman, 1999), including the medial extended amygdala (medial amygdala and medial bed nucleus of the stria terminalis, BSTm), m…”

“Both the hippocampus and LS contain VIP receptors (Goodson et al., 2006), and the hippocampus contains a fairly large population of VIP neurons (Bottjer and Alexander, 1995; Erichsen et al., 1991; Luo et al., 2011).”

“In addition, based on the findings in mice (Hill et al., 2007a; Stack et al., 2008), we hypothesized that VPAC receptor activation would promote approach to novel social stimuli.”

“Furthermore, the medial pallium also shows increased immediate early gene induction in response to both appetitive and consummatory sexual behavior in Japanese quail (Ball and Balthazart, 2001).”

“…by numerous hypothalamic and extrahypothalamic cell groups and is perhaps best known for its role in the stimulation of prolactin release (Christensen and Vleck, 2008; Christian et al., 2007; El Halawani et al., 1996; Lam, 1991; Macnamee et al., 1986; Maney et al., 1999; Vleck and Patrick, 1999).”

“Finally, central VIP release stimulates secretion of adrenocorticotropic hormone and corticosterone, and at least part of this effect ismediated via VIP release in the paraventricular nucleus of the hypothalamus (Alexander and Sander, 1994, 1995).”

“…studies show that levels of plasma prolactin mirror levels of VIP cell density within the infundibular hypothalamus, both of which are highest during egg incubation and rearing, and lowest following nest deprivation and in non-rearing hens (Chaiyachet et al., 2012; Cloues et al., 1990).”

“anterior hypothalamus, AH, and ventromedial hypothalamus, VMH), VIP receptors, cells and/or fibers are also present in many other areas that comprise a social behavior network (Goodson, 2005; Newman, 1999), including the medial extended amygdala (medial amygdala and medial bed nucleus of the stria terminalis, BSTm), m…”

“Peptide circuits of the BSTmandLS are particularly important for grouping behavior and social affiliation in birds and mammals, although this has been primarily studied with regard to the nonapeptides (Curley et al., 2009, 2012; Goodson and Wang, 2006; Goodson et al., 2009a, 2009b, 2012a, 2012c; Kelly et al., 2011; Li…”

“Experimental data in sparrows further indicate that some of this seasonal variation is estrogen-dependent (Wacker et al., 2008), and similarly, VIP mRNA is rapidly upregulated in the hypothalamus and other brain areas by estrogen treatment in rats (Gozes et al., 1989; Kasper et al., 1992).”

“…by numerous hypothalamic and extrahypothalamic cell groups and is perhaps best known for its role in the stimulation of prolactin release (Christensen and Vleck, 2008; Christian et al., 2007; El Halawani et al., 1996; Lam, 1991; Macnamee et al., 1986; Maney et al., 1999; Vleck and Patrick, 1999).”

“Interestingly, the results of a recent anatomical study suggest that the medial pallium in pigeons (which includes the medial nidopallium, mesopallium and apical part of the hyperpallium; areas whichmake up our TEL category), is likely homologous to the mammalian prefrontal cortex, based on 1) the medial pallium's ext…”

“anterior hypothalamus, AH, and ventromedial hypothalamus, VMH), VIP receptors, cells and/or fibers are also present in many other areas that comprise a social behavior network (Goodson, 2005; Newman, 1999), including the medial extended amygdala (medial amygdala and medial bed nucleus of the stria terminalis, BSTm), m…”

“…of the mammalian prefrontal cortex (Divac et al., 1978; Kuroda et al., 1998), and thus it is notable that the dorsomedial thalamus does not project to the caudolateral nidopallium, an area sometimes compared to the prefrontal cortex (for an extensive consideration, see Husband and Shimizu, 2011).”

“Similarly, parallel changes in VIP cell size and prolactin levels are observed during the incubation and brooding stages in ring doves (Cheng and Burke, 1983; Cloues et al., 1990; Goldsmith et al., 1981).”

“…et al., 2012c), 2) VIP manipulations significantly impact social behavior in mice and birds (Goodson et al., 2012b; Hill et al., 2007a, 2007b; Lim et al., 2008; Stack et al., 2008) and 3) the antagonist employed here selectively binds to VPAC, but not PAC1, receptors (Nowak et al., 2003) we…”

“…released by numerous hypothalamic and extrahypothalamic cell groups and is perhaps best known for its role in the stimulation of prolactin release (Christensen and Vleck, 2008; Christian et al., 2007; El Halawani et al., 1996; Lam, 1991; Macnamee et al., 1986; Maney et al., 1999; Vleck and…”

“…in utero in mice via VPAC antagonism and through the use of VIP deficient mothers (VIP +/− or VIP −/−) leads to significant deficits in affiliative behavior, social recognition, social approach and responses to social novelty (Hill et al., 2007a, 2007b; Lim et al., 2008; Stack et al., 2008).”

“…in utero in mice via VPAC antagonism and through the use of VIP deficient mothers (VIP +/− or VIP −/−) leads to significant deficits in affiliative behavior, social recognition, social approach and responses to social novelty (Hill et al., 2007a, 2007b; Lim et al., 2008; Stack et al., 2008).”

“Experimental data in sparrows further indicate that some of this seasonal variation is estrogen-dependent (Wacker et al., 2008), and similarly, VIP mRNA is rapidly upregulated in the hypothalamus and other brain areas by estrogen treatment in rats (Gozes et al., 1989; Kasper et al., 1992).”

“Interestingly, VIP-induced prolactin secretion is reduced by testosterone, apparently at the level of the pituitary (Knapp et al., 1988), suggesting a potential mechanism for the tradeoffs commonly observed between testosterone-mediated behaviors (e.g., aggression) and parental behavior (McGlothlin…”

“Experimental data in sparrows further indicate that some of this seasonal variation is estrogen-dependent (Wacker et al., 2008), and similarly, VIP mRNA is rapidly upregulated in the hypothalamus and other brain areas by estrogen treatment in rats (Gozes et al., 1989; Kasper et al., 1992).”

“However, the exposure of low novelty-seeking versus high novelty-seekingmice to an intruder in their homecage differentially activates these same brain areas, suggesting that novelty seeking behavior may impact responses to social stimuli (Clinton et al., 2011).”

“…studies show that levels of plasma prolactin mirror levels of VIP cell density within the infundibular hypothalamus, both of which are highest during egg incubation and rearing, and lowest following nest deprivation and in non-rearing hens (Chaiyachet et al., 2012; Cloues et al., 1990).”

“Of note is that PACAP also acts through a single PACAP receptor, PAC1, which binds PACAP with high affinity and VIP with very poor affinity (Vaudry et al., 2000; Zawilska et al., 2003).”

“The selective VPAC receptor antagonist used in the present study, neurotensin6–11 mouseVIP7–28, is known to blockVIP stimulation of cyclic AMP production in chick brain slices without blocking PAC1 receptors (Nowak et al., 2003) and also produces behavioral effects in vivo that mirror those of antisense-mediated VIP k…”

“Finally, central VIP release stimulates secretion of adrenocorticotropic hormone and corticosterone, and at least part of this effect ismediated via VIP release in the paraventricular nucleus of the hypothalamus (Alexander and Sander, 1994, 1995).”

“Moreover, blockade of the vasoactive intestinal polypeptide receptor in the brain of zebra finches alters social contact behavior in a novel, but not familiar, environment (Kingsbury et al., 2013).”

“2003) or saline control into the medial nidopallium of both male and female zebra finches and examined whether each subject chose to affiliate with 2 or 10 unfamiliar same-sex conspecifics (Kingsbury et al. 2013).”

“, 2012a); social contact, gregariousness, and pair bonding in zebra finches (Kingsbury et al., 2013; Kingsbury and Goodson, 2014); and social recognition and sociability in mice (Hill et al.”

“Intracerebroventricular infusions of VPAC receptor antagonist (neurotensin6-11 mouse VIP7–28) in gregarious finches reduced social contact when animals were tested in a novel environment but did not modulate general anxiety-like behavior (Kingsbury et al. 2013).”

“In birds (zebra finches, Taeniopygia guttata), VIP was found to inhibit aggressive behavior (Goodson and AdkinsRegan, 1999) and to modulate gregariousness (Kingsbury et al., 2013).”