TY - JOUR
T1 - Oxytocin receptor activation does not mediate associative fear deficits in a Williams Syndrome model
AU - Nygaard, Kayla R.
AU - Swift, Raylynn G.
AU - Glick, Rebecca M.
AU - Wagner, Rachael E.
AU - Maloney, Susan
AU - Gould, Georgianna G.
AU - Dougherty, Joseph D.
N1 - Funding Information:
National Institute of Child Health and Human Development, Grant/Award Number: P50HD103525; National Institute of Mental Health, Grant/Award Number: 5R01MH107515‐05; National Science Foundation, Grant/Award Number: DGE‐1745038; San Antonio Area Foundation; The Morrison Trust Funding information
Funding Information:
We would like to thank N. Kopp for his contributions and support, E. Minakova and D. Burek for surgical training and H.A. Stephens, Y.R. Sanchez, M.C. Nunn and B.L. Pierce for their expert technical assistance in tissue preparation. CD mice were a generous gift from V. Campuzano. The Animal Behavior Core at Washington University in St. Louis graciously shared their resources. Financial support was provided by the NIMH 5R01MH107515‐05 (JDD), NSF DGE‐1745038 (KRN), NICHD P50HD103525 (IDDRC@WUSTL) and John L. Santikos Charitable Foundation of the San Antonio Area Foundation and The Morrison Trust (GGG). The authors declare no competing financial interests.
Publisher Copyright:
© 2021 International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.
PY - 2022/1
Y1 - 2022/1
N2 - Williams Syndrome results in distinct behavioral phenotypes, which include learning deficits, anxiety, increased phobias and hypersociability. While the underlying mechanisms driving this subset of phenotypes is unknown, oxytocin (OT) dysregulation is hypothesized to be involved as some studies have shown elevated blood OT and altered OT receptor expression in patients. A “Complete Deletion” (CD) mouse, modeling the hemizygous deletion in Williams Syndrome, recapitulates many of the phenotypes present in humans. These CD mice also exhibit impaired fear responses in the conditioned fear task. Here, we address whether OT dysregulation is responsible for this impaired associative fear memory response. We show direct delivery of an OT receptor antagonist to the central nervous system did not rescue the attenuated contextual or cued fear memory responses in CD mice. Thus, increased OT signaling is not acutely responsible for this phenotype. We also evaluated OT receptor and serotonin transporter availability in regions related to fear learning, memory and sociability using autoradiography in wild type and CD mice. While no differences withstood correction, we identified regions that may warrant further investigation. There was a nonsignificant decrease in OT receptor expression in the lateral septal nucleus and nonsignificant lowered serotonin transporter availability in the striatum and orbitofrontal cortex. Together, these data suggest the fear conditioning anomalies in the Williams Syndrome mouse model are independent of any alterations in the oxytocinergic system caused by deletion of the Williams locus.
AB - Williams Syndrome results in distinct behavioral phenotypes, which include learning deficits, anxiety, increased phobias and hypersociability. While the underlying mechanisms driving this subset of phenotypes is unknown, oxytocin (OT) dysregulation is hypothesized to be involved as some studies have shown elevated blood OT and altered OT receptor expression in patients. A “Complete Deletion” (CD) mouse, modeling the hemizygous deletion in Williams Syndrome, recapitulates many of the phenotypes present in humans. These CD mice also exhibit impaired fear responses in the conditioned fear task. Here, we address whether OT dysregulation is responsible for this impaired associative fear memory response. We show direct delivery of an OT receptor antagonist to the central nervous system did not rescue the attenuated contextual or cued fear memory responses in CD mice. Thus, increased OT signaling is not acutely responsible for this phenotype. We also evaluated OT receptor and serotonin transporter availability in regions related to fear learning, memory and sociability using autoradiography in wild type and CD mice. While no differences withstood correction, we identified regions that may warrant further investigation. There was a nonsignificant decrease in OT receptor expression in the lateral septal nucleus and nonsignificant lowered serotonin transporter availability in the striatum and orbitofrontal cortex. Together, these data suggest the fear conditioning anomalies in the Williams Syndrome mouse model are independent of any alterations in the oxytocinergic system caused by deletion of the Williams locus.
UR - http://www.scopus.com/inward/record.url?scp=85107446889&partnerID=8YFLogxK
U2 - 10.1111/gbb.12750
DO - 10.1111/gbb.12750
M3 - Article
C2 - 33978321
AN - SCOPUS:85107446889
SN - 1601-1848
VL - 21
JO - Genes, Brain and Behavior
JF - Genes, Brain and Behavior
IS - 1
M1 - e12750
ER -