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T R Insel

Publications and source records attributed to T R Insel.

At least 37 records · Page 2Linked to original sources
PubMed2000

Social amnesia in mice lacking the oxytocin gene.

The development of social familiarity in rodents depends predominantly on olfactory cues and can critically influence reproductive success. Researchers have operationally defined this memory by a reliable decrease in olfactory investigation in repeated or prolonged encounters with a conspecific. Brain oxytocin (OT) and vasopressin (AVP) seem to modulate a range of social behaviour from parental care to mate guarding. Pharmacological studies indicate that AVP administration may enhance social memory, whereas OT administration may either inhibit or facilitate social memory depending on dose, route or paradigm. We found that male mice mutant for the oxytocin gene (Oxt-/-) failed to develop social memory, whereas wild-type (Oxt+/+) mice showed intact social memory. Measurement of both olfactory foraging and olfactory habituation tasks indicated that olfactory detection of non-social stimuli is intact in Oxt-/- mice. Spatial memory and behavioural inhibition measured in a Morris water-maze, Y-maze, or habituation of an acoustic startle also seemed intact. Treatment with OT but not AVP rescued social memory in Oxt-/- mice, and treatment with an OT antagonist produced a social amnesia-like effect in Oxt+/+ mice. Our data indicate that OT is necessary for the normal development of social memory in mice and support the hypothesis that social memory has a neural basis distinct from other forms of memory.

Amnesia, Retrograde↗
PubMed2000

Hypothalamic vasopressin gene expression increases in both males and females postpartum in a biparental rodent.

In previous studies, the closely related neuropeptide hormones oxytocin and vasopressin have been implicated in the central mediation of parental behaviour. Several studies in rats and sheep have demonstrated a role for oxytocin in the initiation of maternal behaviour. Recently, a few studies in a biparental species, the prairie vole (Microxytocinus ochrogaster) have suggested that vasopressin is important for paternal care. The present study investigated this latter possibility by measuring changes in vasopressin and oxytocin hypothalamic gene expression 1 day and 6 days following parturition in prairie voles which show paternal care and in montane voles (M. montanus) which lack paternal care. In prairie voles, vasopressin gene expression increased in both males and females postpartum, relative to sexually naive controls. In the non-paternal montane vole, no change in vasopressin gene expression was observed in either sex. In contrast to this species difference in vasopressin gene expression, hypothalamic oxytocin gene expression increased in both prairie and montane vole females, but not in males of either species. To augment measures of gene expression, we assessed vasopressin (V1a) and oxytocin receptor binding in both species. Although forebrain vasopressin V1a receptor binding was not altered following parturition in either species, oxytocin receptor binding increased in the ventromedial nucleus of the hypothalamus in females, but not males, in both prairie and montane voles. In summary, vasopressin gene expression increases in both males and females postpartum in a biparental species and oxytocin gene expression and receptor binding increase selectively in females. These results are consistent with earlier reports of a role for vasopressin in paternal care and for oxytocin in maternal behaviour.

Animals↗
PubMed1999

Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole.

Arginine vasopressin influences male reproductive and social behaviours in several vertebrate taxa through its actions at the V1a receptor in the brain. The neuroanatomical distribution of vasopressin V1a receptors varies greatly between species with different forms of social organization. Here we show that centrally administered arginine vasopressin increases affiliative behaviour in the highly social, monogamous prairie vole, but not in the relatively asocial, promiscuous montane vole. Molecular analyses indicate that gene duplication and/or changes in promoter structure of the prairie vole receptor gene may contribute to the species differences in vasopressin-receptor expression. We further show that mice that are transgenic for the prairie vole receptor gene have a neuroanatomical pattern of receptor binding that is similar to that of the prairie vole, and exhibit increased affiliative behaviour after injection with arginine vasopressin. These data indicate that the pattern of V1a-receptor gene expression in the brain may be functionally associated with species-typical social behaviours in male vertebrates.

Animals↗
PubMed1999

Autoradiographic and in situ hybridization localization of corticotropin-releasing factor 1 and 2 receptors in nonhuman primate brain.

Two different corticotropin-releasing factor (CRF) receptors, CRF1 and CRF2, have been identified in rat and human brain. Although the two receptor subtypes show a markedly different distribution in the rat brain, their distribution in the primate brain has not been described previously. In this study, the neuroanatomic distribution of CRF1 and CRF2 receptor binding sites in rhesus monkey (Macaca mulatta) was assessed by using iodine 125 ([125I)-Tyr0]-sauvagine with or without the selective CRF1 receptor antagonist CP-154,526-1. Radiolabeled human cRNA probes were used to map the distribution of the two receptor mRNAs with in situ hybridization. Both CRF1 and CRF2 receptors were found in the pituitary and throughout the neocortex (especially, in prefrontal, cingulate, striate, and insular cortices), amygdala, and hippocampal formation of the monkey brain. This is in contrast to the distribution of these receptors reported in the rat brain, in which generally only the CRF1 receptor is found in the pituitary and neocortex. These results suggest that, in primates, both CRF1 and CRF2 receptors may be involved in mediating the effects of CRF on cognition, behavior, and pituitary-adrenal function. The presence of CRF1 (but not CRF2) receptors within the locus coeruleus, cerebellar cortex, nucleus of the solitary tract, thalamus, and striatum and of CRF2 (but not CRF1) receptors in the choroid plexus, certain hypothalamic nuclei, the nucleus prepositus, and the nucleus of the stria terminalis suggests that each receptor subtype also may have distinct functional roles within the primate central nervous system.

Amphibian Proteins↗
PubMed1999

Differential expansion of neural projection systems in primate brain evolution.

Whole brain MRI scans from 11 primate species (43 individuals) spanning more than a 50-fold range in brain volume were used to determine whether the corpus callosum keeps pace with the growth of the forebrain among living anthropoid primates. Interhemispheric connectivity via the corpus callosum and anterior commissure was reduced in larger primate brains, whereas intrahemispheric connectivity was augmented. We also show that the splenium constitutes an increasing proportion of callosal area with increasing brain size. This may function to maintain rapid integration of the left and right visual space as brain size increases. These results indicate that the evolution of larger brain size in primates results in increasingly independent hemispheres.

Animals↗
PubMed1999

Oxytocin, vasopressin, and autism: is there a connection?

Autism is a poorly understood developmental disorder characterized by social impairment, communication deficits, and compulsive behavior. The authors review evidence from animal studies demonstrating that the nonapeptides, oxytocin and vasopressin, have unique effects on the normal expression of species-typical social behavior, communication, and rituals. Based on this evidence, they hypothesize that an abnormality in oxytocin or vasopressin neurotransmission may account for several features of autism. As autism appears to be a genetic disorder, mutations in the various peptide, peptide receptor, or lineage-specific developmental genes could lead to altered oxytocin or vasopressin neurotransmission. Many of these genes have been cloned and sequenced, and several polymorphisms have been identified. Recent gene targeting studies that alter expression of either the peptides or their receptors in the rodent brain partially support the autism hypothesis. While previous experience suggests caution in hypothesizing a cause or suggesting a treatment for autism, the available preclinical evidence with oxytocin and vasopressin recommends the need for clinical studies using gene scanning, pharmacological and neurobiological approaches.

Autistic Disorder↗
PubMed1999

The primate neocortex in comparative perspective using magnetic resonance imaging.

In this study we use neuroanatomic data from living anthropoid primate subjects to test the following three hypotheses: (1) that the human neocortex is significantly larger than expected for a primate of our brain size, (2) that the human prefrontal cortex is significantly more convoluted than expected for our brain size, and (3) that increases in cerebral white matter volume outpace increases in neocortical gray matter volume among anthropoid primates. Whole brain MRI scans were obtained from 44 living primate subjects from 11 different species. Image analysis software was used to calculate total brain volume, neocortical gray matter volume, cerebral white matter volume, and the cross sectional area of the spinal cord in each scan. Allometric regression analyses were used to compare the relative size of these brain structures across species, with an emphasis on determining whether human brain proportions correspond with predictions based on nonhuman primate allometric trajectories. All three hypotheses were supported by our analysis. The results of this study provide additional insights into human brain evolution beyond the important observation that brain volume approximately tripled in the hominid lineage by demonstrating that the neocortex was uniquely modified throughout hominid evolution. These modifications may constitute part of the neurobiological substrate that supports some of our species most distinctive cognitive abilities.

Animals↗
PubMed1999

Dopamine D2 receptor-mediated regulation of partner preferences in female prairie voles (Microtus ochrogaster): a mechanism for pair bonding?

This study examined the role of dopamine (DA) in partner preference (PP) formation in female prairie voles (Microtus ochrogaster). The nonspecific DA antagonist haloperidol blocked mating-induced PP, whereas the nonspecific DA agonist apomorphine induced PP without mating. The D2 antagonist eticlopride, but not the D1 antagonist SCH23390, blocked PP, whereas the D2 agonist quinpirole, but not the D1 agonist SKF38393, induced PP without mating. Injections of eticlopride before or immediately after mating, but not 24 hr after mating, impaired PP, indicating that DA's effects were not due to an interference with mating or sensory recognition. Finally, intracerebroventricular injections of eticlopride diminished PP. Together, these data suggest that mating-induced PP requires activation of D2 receptors and that social experience may activate dopaminergic pathways, with enduring effects on behavior.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

Localization of vasopressin (V1a) receptor binding and mRNA in the rhesus monkey brain.

Centrally released arginine vasopressin (AVP) has been associated with various behavioural and cognitive effects, such as scent marking, aggression, and memory, which are believed to be mediated by the V1a subtype of the vasopressin receptor. Although the distribution of V1a receptors is conserved in a few brain regions, the pattern of expression of this receptor is, in general, highly species-specific. We have used receptor autoradiography with the linear V1a receptor ligand (125I-Phenylacetyl-D-Tyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-Tyr-NH2) to characterize the pattern of receptor binding in the rhesus monkey brain. Brain sites of V1a receptor synthesis were defined using in-situ hybridization. The regions of highest V1a receptor density included the prefrontal, cingulate, pyriform, and entorhinal cortex, as well as the presubiculum and mamillary bodies. In addition, V1a receptor binding and mRNA were detected in several regions reported to have V1a receptor in most rodents, including the amygdala, bed nucleus of the stria terminalis, lateral septum, hypothalamus and the brainstem. The distribution is consistent with a role for vasopressin in higher cognitive functions, especially memory, in primates.

Amino Acid Sequence↗
PubMed1998

Serotonin and neuropeptides in affiliative behaviors.

The neuropharmacological study of serotonin and behavior has followed two fundamentally different strategies. One approach has used behavior as a dependent variable for assaying drug effects. To characterize serotonergic drugs, most studies have used relatively simple behaviors, such as locomotor activity, startle, exploration, operant responses, and sleep. A second approach has focused on behavior, with drugs used as tools to elucidate the physiological role of serotonin. These studies have increasingly focused on behaviors of ethological importance, including aggression, sexual behavior, and other forms of social interaction. Here we review studies using this approach to focus on one particular kind of social interaction: affiliation.

Animals↗
PubMed1998

Oxytocin, vasopressin, and the neuroendocrine basis of pair bond formation.

Several lines of evidence support a role for oxytocin and vasopressin in complex social behaviors, including parental care, sex behavior, and aggression. Recent studies in a monogamous mammal, the prairie vole, suggest an additional role for both peptides in the formation of pair bonds. Central administration of oxytocin facilitates and administration of an oxytocin antagonist inhibits partner preference formation in female prairie voles. Conversely, vasopressin facilitates and a V1a receptor antagonist inhibits pair bonding in males. A potential cellular basis for these effects is the species-specific pattern of expression of oxytocin and V1a receptor in reward pathways of the prairie vole brain. At a molecular level, comparative sequencing of the oxytocin and V1a receptors reveals species differences in the promoter sequences that may guide regional expression in the brain. Transgenic mice created with the 5' flanking region of the prairie vole oxytocin receptor gene demonstrate that sequencing in this region influence the pattern of expression within the brain. The unique promoter sequences of the prairie vole OTR and V1a receptor genes and the resulting species-specific pattern of regional expression provide a potential molecular mechanism for the evolution of pair bonding behaviors and a cellular basis for monogamy.

Animals↗
PubMed1998

Voles and vasopressin: a review of molecular, cellular, and behavioral studies of pair bonding and paternal behaviors.

Several lines of evidence have implicated the neurohypophyseal peptide, vasopressin (VP), in the mediation of complex social behaviors including affiliation, aggression, juvenile recognition and parental behavior. Recent studies in microtine rodents using cellular, molecular and behavioral approaches provide additional evidence suggesting a role for VP in the formation of pair bonding and male parental care. Monogamous and promiscuous voles differ in social behaviors such as mating-induced pair bonding, selective aggression, and male parental care. Comparative studies have demonstrated that they also differ in dynamics of VP synthesis and release associated with reproduction, in the distribution pattern and regional quantity of VP receptors, and in the promoter sequence of the V1a receptor gene. In monogamous prairie voles, (Microtus ochrogaster), brain administration of VP induces pair bonding and male parental care whereas administration of the VP antagonist diminishes these behaviors. Together, these data suggest that VP is involved in the regulation of social behaviors in monogamous voles and differences in the brain VP system may underlie species differences in behavior and life strategy in voles.

Animals↗
PubMed1998

Neuroendocrine bases of monogamy.

A number of studies have implicated the neurohypophyseal peptides oxytocin and vasopressin in the central mediation of complex social behaviors, including affiliation, parental care and territorial aggression. Research on a monogamous rodent, the prairie vole (Microtus ochrogaster), suggests that these neuropeptides are also involved in the control of several behaviors associated with monogamy, including pair bonding, paternal care and mate guarding. Comparative studies using several species of vole have identified species-specific patterns of oxytocin- and vasopressin-receptor expression in the brain that appear to be associated with a monogamous versus non-monogamous social structure. Molecular studies suggest that changes in the regulation of oxytocin- and vasopressin-receptor gene expression underlie these species differences in receptor distribution and might provide a mechanism for the evolution of monogamy in voles.

Animals↗
PubMed1998

Evolution of the cerebellum in primates: differences in relative volume among monkeys, apes and humans.

According to the 'developmental constraint hypothesis' of comparative mammalian neuroanatomy, brain structures enlarge predictably as the entire brain grows both ontogenetically and phylogenetically. In this study, brain and cerebellum volumes are measured from in vivo magnetic resonance scans of 44 primates from 11 haplorhine species. After controlling for overall brain volume, the cerebellum in both pongid and hylobatid apes is, on average, 45% larger than in monkeys. These results demonstrate that all primate brains are not similarly organized and that developmental constraints are not tight enough to preclude selection for increased cerebellar volume independent of selection on overall brain size.

Animals↗
PubMed1997

Vasopressin in the forebrain of common marmosets (Callithrix jacchus): studies with in situ hybridization, immunocytochemistry and receptor autoradiography.

The distribution of vasopressin (AVP) producing cells, their projections and AVP receptors was examined in the brain of common marmosets (Callithrix jacchus) using in situ hybridization, immunocytochemistry and receptor autoradiography. Clusters of cells labeled for AVP mRNA or stained for AVP immunoreactivity (AVP-ir) were found in the paraventricular (PVN), supraoptic (SON) and suprachiasmatic nuclei (SCN) of the hypothalamus. Scattered AVP producing cells were also found in the lateral hypothalamus and the bed nucleus of the stria terminalis (BST). Neither AVP mRNA-labeled nor AVP-ir cells were detected in the amygdala. Although AVP-ir fibers were evident outside of the hypothalamic-neurohypophyseal tract, a plexus of fibers in the lateral septum, as observed in the rat brain, was not detected. Receptor autoradiography using 125I-linear-AVP revealed specific binding for AVP receptors in the nucleus accumbens, diagonal band, lateral septum, the BST, SCN, PVN, amygdala, anterodorsal and ventromedial nucleus of the hypothalamus, indicating sites for central AVP action in the marmoset brain. Together, these data provide a comprehensive picture of AVP pathways in the marmoset brain, demonstrating differences from rodents in the distribution of cell bodies, fibers and receptors.

Animals↗
PubMed1997

Sexual and social experience is associated with different patterns of behavior and neural activation in male prairie voles.

Monogamous prairie voles (Microtus ochrogaster) show mating-induced aggression towards conspecific strangers. This behavior is both selective and enduring. The present study was designed to investigate the behavioral conditions for the emergence of selective aggression (by varying prior experience with a female and identity of intruders) and the limbic activation in response to an intruder (by mapping regional staining for c-fos) in male prairie voles. In a first experiment, males that mated with a female for 24 h exhibited aggression towards a male intruder and had more Fos-immunoreactive (Fos-ir) cells in the medial amygdala (AMYGme) and medial preoptic area (MPO) relative to males that cohabited with a female without mating or that had no prior exposure to a female. Cohabited males did not become aggressive. However, these males along with mated males had an increased number of Fos-ir cells in the lateral septum (LS) and the bed nucleus of the stria terminalis (BST) relative to males without prior exposure to a female. In a second experiment, mated males exhibited more offensive aggression to a male intruder but more defensive aggression to a female intruder. Both types of aggression, however, induced an increase in the number of Fos-ir cells in the AMYGme. In addition, Fos-ir staining in the BST was induced selectively in response to a male intruder and a similar trend was found in the LS. Exposure to a male or female intruder did not increase Fos-ir staining in the MPO. Taken together, our data suggest the neural substrates activated by social/sexual activity and involved in response to intruders. The AMYGme was involved in processing intruder-related cues and/or in the regulation of aggressive response to both male and female intruders. The BST and LS were modulated by social experience with a female (mating or cohabitation) and were responsive to male-related cues even in the absence of aggression. Finally, the MPO was activated at different magnitudes by social or sexual experience but did not respond to intruder-related cues as measured by Fos-ir.

Amygdala↗
PubMed1997

Species differences in vasopressin receptor binding are evident early in development: comparative anatomic studies in prairie and montane voles.

Monogamous prairie voles (Microtus ochrogaster) and promiscuous montane voles (Microtus montanus) exhibit remarkable differences in the distribution of vasopressin (AVP) receptors in the adult brain. This difference in receptor distribution is associated with species differences in the behaviors, including pair bond formation and paternal care, found selectively in the monogamous vole. To investigate a potential mechanism for this species difference in AVP receptors, the present study examined the ontogeny of receptor binding in the two species to determine whether the adult maps arose from a shared pattern in development. By using 125I-linear-AVP, which is a selective high-affinity ligand for the V1a receptor, we found early appearance and transient expression of AVP receptor binding during postnatal development in both species. However, the ontogenetic patterns of regional AVP receptor binding were species specific. In the diagonal band, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala, prairie voles had higher AVP receptor binding at birth than montane voles, and this difference persisted with little variation into adulthood. In these areas, therefore, species differences in AVP receptor binding appeared to be determined primarily by genetic or prenatal factors. In the lateral septum, both species had low levels of AVP receptor binding at birth. Thereafter, the binding increased rapidly in montane voles, but it remained unchanged in prairie voles. In the cingulate cortex, AVP receptor binding in prairie voles showed a peak in early development with a subsequent decline and reached the adult level at weaning, whereas the binding in montane voles remained unchanged into adulthood. A similar but opposite pattern was found in the frontoparietal cortex, in which AVP receptor binding showed an early peak in montane voles but did not change significantly in prairie voles. These results demonstrate that 1) species differences in regional AVP receptor binding are evident in the early postnatal period and, in several areas, may be determined by genetic or prenatal factors, and 2) AVP may target brain areas differently in infant and adult prairie and montane voles and, thus, could exert differential effects on the organization of the central nervous system in the two species of voles.

Aging↗