Publications (28) View all
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Article: Vasopressin eliminates the expression of familiar odor bias in neonatal female mice through V1aR.
Elizabeth A D Hammock, Caitlin S Law, Pat Levitt[show abstract] [hide abstract]
ABSTRACT: Arginine-vasopressin (AVP) and the vasopressin V1a receptor (V1aR) acting within the forebrain are involved in social behavior in adult animals. Much less is known about the function of V1aR in neurobehavioral development. In the present study, at post-natal day 8 (P8) in neonatal C57BL/6J mice, we map V1aR and use an olfactory exposure paradigm to assess a role for V1aR on olfactory preferences. In addition to V1aR in the lateral septum and ventral tegmental area, we observe V1aR in the neocortex and hippocampus, not typically observed in adult mice, implicating a developmental sensitive period for V1aR to modulate these brain areas in an experience-dependent manner. Males and females were tested on P8 for orienting preferences after exposure to a non-social odor, presented either when the mother was in the home cage (contingent) or when the mother had been removed from the home cage (not contingent). Wild-type female mice show a selective orienting bias toward the exposed odor, but only in the contingent condition. Males did not show orienting bias after either training condition. Female Avpr1a(-/-) mice showed strong familiar odor bias, regardless of the training condition. This finding led us to test the ability of AVP to diminish odor bias in females. Central application of AVP eliminated odor bias in Avpr1a(+/+), but not Avpr1a(-/-) female mice. Together, these data indicate that AVP acting at V1aR eliminates the expression of familiar odor bias in neonatal mice. This suggests a developmental role for AVP on familiarity bias, which has implications for species-typical life history trajectories of social learning and natal dispersal.Hormones and Behavior 12/2012; · 3.87 Impact Factor -
Article: Modulation of parvalbumin interneuron number by developmentally transient neocortical vasopressin receptor 1a (V1aR).
E A D Hammock, P Levitt[show abstract] [hide abstract]
ABSTRACT: Arginine-vasopressin (AVP) and the vasopressin 1a receptor (V1aR) modulate social behavior and learning and memory in adult animals. Both functions depend upon the normal emergence of the balance of excitation and inhibition (E/I balance) in the neocortex. Here, we tested the hypothesis that V1aR signaling and E/I balance converge through the influence of the neuropeptide on interneuron number achieved in the neocortex. Postnatal mapping of forebrain V1aR binding in male and female mice revealed a transient expression of high levels of receptor in the neocortex and hippocampus in the second and third post-natal weeks. Receptor binding levels in these cortical structures fell dramatically in the adult, maintaining high levels of expression subcortically. Surprisingly, we observed sex differences in the number of calbindin interneurons, and a contribution of V1aR to the number of parvalbumin-immunoreactive neurons in the adult mouse neocortex. These data suggest that individual differences in developmentally transient V1aR signaling and even sex may alter the development of E/I balance in the neocortex, with long-lasting influence on information processing.Neuroscience 07/2012; 222:20-8. · 3.38 Impact Factor -
Article: One-month-old human infants learn about the social world while they sleep.
Bethany C Reeb-Sutherland, William P Fifer, Dana L Byrd, Elizabeth A D Hammock, Pat Levitt, Nathan A Fox[show abstract] [hide abstract]
ABSTRACT: Although infants display preferences for social stimuli early in their lives, we know relatively little about the mechanisms of infant learning about the social world. In the current set of studies, 1-month-old infants underwent an adapted eyeblink conditioning paradigm to examine learning to both 'social' and non-social cues. While infants were asleep, they were presented with either a 'social' stimulus (a female voice) or one of two non-social stimuli (tone or backward voice) followed by an airpuff presented to the eyelid. Infants in the experimental groups displayed increased learning across trials, regardless of stimulus type. However, infants conditioned to the 'social' stimulus showed increased learning compared to infants conditioned to either of the non-social stimuli. These results suggest a mechanism by which learning about the social world occurs early in life and the power of ecologically valid cues in facilitating that learning.Developmental Science 09/2011; 14(5):1134-41. · 3.89 Impact Factor -
Article: Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder.
Daniel B Campbell, Dibyadeep Datta, Shaine T Jones, Evon Batey Lee, James S Sutcliffe, Elizabeth A D Hammock, Pat Levitt[show abstract] [hide abstract]
ABSTRACT: Autism spectrum disorder (ASD) is characterized by core deficits in social behavior, communication, and behavioral flexibility. Several lines of evidence indicate that oxytocin, signaling through its receptor (OXTR), is important in a wide range of social behaviors. In attempts to determine whether genetic variations in the oxytocin signaling system contribute to ASD susceptibility, seven recent reports indicated association of common genetic polymorphisms in the OXTR gene with ASD. Each involved relatively small sample sizes (57 to 436 families) and, where it was examined, failed to identify association of OXTR polymorphisms with measures of social behavior in individuals with ASD. We report genetic association analysis of 25 markers spanning the OXTR locus in 1,238 pedigrees including 2,333 individuals with ASD. Association of three markers previously implicated in ASD susceptibility, rs2268493 (P = 0.043), rs1042778 (P = 0.037), and rs7632287 (P = 0.016), was observed. Further, these genetic markers were associated with multiple core ASD phenotypes, including social domain dysfunction, measured by standardized instruments used to diagnose and describe ASD. The data suggest association of OXTR genetic polymorphisms with ASD, although the results should be interpreted with caution because none of the significant associations would survive appropriate correction for multiple comparisons. However, the current findings of association in a large independent cohort are consistent with previous results, and the biological plausibility of participation of the oxytocin signaling system in modulating social disruptions characteristic of ASD, suggest that functional polymorphisms of OXTR may contribute to ASD risk in a subset of families.Journal of Neurodevelopmental Disorders 06/2011; 3(2):101-12. · 3.06 Impact Factor -
Article: Developmental expression mapping of a gene implicated in multiple neurodevelopmental disorders, A2bp1 (Fox1).
Elizabeth A D Hammock, Pat Levitt[show abstract] [hide abstract]
ABSTRACT: The neuronal transcription splicing factor, A2BP1, has been implicated in a variety of neurodevelopmental disorders; however, the role of A2BP1 in brain development and gene regulatory function remains to be explicated. Here, we map A2bp1 gene expression, focusing on the developing forebrain of the C57BL6J mouse. Early in forebrain development, A2bp1 expression is highly reminiscent of the expression of genes marking postmitotic GABAergic cells emanating from the ventral telencephalon during migration to the dorsal pallium. Ventral pallial expression remains low after the migratory period. Broader dorsal pallial expression becomes more evident late prenatally and early postnatally. This is paralleled by dense, restricted expression in the ventrobasal dorsal thalamic complex and mid-hypothalamic region. Outside of the forebrain, there is significant expression in motor pathways. These data indicate that A2BP1 mutations may clinically affect very selective forebrain neuron types from early periods of development.Developmental Neuroscience 02/2011; 33(1):64-74. · 3.63 Impact Factor