Galanin neurons in the medial preoptic area govern parental behavior

Mice display robust, stereotyped behaviours towards pups: virgin males typically attack pups, whereas virgin females and sexually experienced males and females display parental care. Here we show that virgin males genetically impaired in vomeronasal sensing do not attack pups and are parental. Furthermore, we uncover a subset of galanin-expressing neurons in the medial preoptic area (MPOA) that are specifically activated during male and female parenting, and a different subpopulation that is activated during mating. Genetic ablation of MPOA galanin neurons results in marked impairment of parental responses in males and females and affects male mating. Optogenetic activation of these neurons in virgin males suppresses inter-male and pup-directed aggression and induces pup grooming. Thus, MPOA galanin neurons emerge as an essential regulatory node of male and female parenting behaviour and other social responses. These results provide an entry point to a circuit-level dissection of parental behaviour and its modulation by social experience.

[1]  J. Rosenblatt,et al.  Maternal behavior induced by maternal blood plasma injected into virgin rats. , 1968, Journal of comparative and physiological psychology.

[2]  L. Swanson,et al.  The organization of neural inputs to the medial preoptic nucleus of the rat , 1986, The Journal of comparative neurology.

[3]  R. Gorski,et al.  Effects of discrete lesions of the sexually dimorphic nucleus of the preoptic area or other medial preoptic regions on the sexual behavior of male rats , 1983, Brain Research Bulletin.

[4]  T. Insel,et al.  The neurobiology of attachment , 2001, Nature Reviews Neuroscience.

[5]  I. Merchenthaler,et al.  Galanin and the neuroendocrine axes. , 2010, Experientia supplementum.

[6]  P. Conn,et al.  Gonadotropin-Releasing Hormone and Its Receptors in Rat Brain , 1994, Frontiers in Neuroendocrinology.

[7]  L. Swanson,et al.  Neurotransmitter specificity of cells and fibers in the medial preoptic nucleus: An immunohistochentical study in the rat , 1986, The Journal of comparative neurology.

[8]  B. O’Malley,et al.  Progesterone receptors mediate male aggression toward infants , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[9]  F. V. vom Saal.  Time-contingent change in infanticide and parental behavior induced by ejaculation in male mice. , 1985, Physiology & behavior.

[10]  S. Nakanishi,et al.  Presynaptic localization of a metabotropic glutamate receptor, mGluR7, in the primary afferent neurons: an immunohistochemical study in the rat , 1995, Neuroscience Letters.

[11]  W. Young,et al.  Oxytocin: The great facilitator of life , 2009, Progress in Neurobiology.

[12]  B. Svare,et al.  Infanticide: Genetic, developmental and hormonal influences in mice , 1981, Physiology & Behavior.

[13]  A. Fleming,et al.  Vomeronasal and olfactory system modulation of maternal behavior in the rat. , 1979, Science.

[14]  K. Kelliher,et al.  Sexually Dimorphic Activation of Galanin Neurones in the Ferret's Dorsomedial Preoptic Area/Anterior Hypothalamus after Mating , 2002, Journal of neuroendocrinology.

[15]  I. Weaver,et al.  Natural variations in maternal care are associated with estrogen receptor alpha expression and estrogen sensitivity in the medial preoptic area. , 2003, Endocrinology.

[16]  J. Rosenblatt.  Nonhormonal Basis of Maternal Behavior in the Rat , 1967, Science.

[17]  Bruce L. McNaughton,et al.  Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles , 1999, Nature Neuroscience.

[18]  T. Holy,et al.  Loss of sex discrimination and male-male aggression in mice deficient for TRP2. , 2002, Nature Reviews Genetics.

[19]  P. Doherty,et al.  Prolactin stimulation of maternal behavior in female rats. , 1985, Science.

[20]  M. Leon,et al.  Hormonal induction of maternal behavior in the ovariectomized nulliparous rat. , 1970, Physiology & behavior.

[21]  R. Elwood,et al.  The inhibition of infanticide and the onset of paternal care in male mice Mus musculus. , 1985 .

[22]  D. Pfaff,et al.  Facilitation of the lordosis reflex of female rats from the ventromedial nucleus of the hypothalamus. , 1979, The Journal of physiology.

[23]  L. Schwarzkopf,et al.  Factors affecting incidence of infanticide and discrimination of related and unrelated neonates in male Mus musculus. , 1983, Behavioral and neural biology.

[24]  K. Kardong,et al.  The role of the vomeronasal organ in rattlesnake (Crotalus viridis oreganus) predatory behavior. , 1996, Brain, behavior and evolution.

[25]  Murtaza Z Mogri,et al.  Optical Deconstruction of Parkinsonian Neural Circuitry , 2009, Science.

[26]  Shakti Sharma,et al.  Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[27]  C. Pedersen,et al.  Oxytocin induces maternal behavior in virgin female rats. , 1982, Science.

[28]  L. Swanson,et al.  Projections of the medial preoptic nucleus: A Phaseolus vulgaris leucoagglutinin anterograde tract‐tracing study in the rat , 1988, The Journal of comparative neurology.

[29]  J. Betley,et al.  Parallel, Redundant Circuit Organization for Homeostatic Control of Feeding Behavior , 2013, Cell.

[30]  J. Milne,et al.  An integrative approach , 1995 .

[31]  F. Talamantes,et al.  Galanin regulates prolactin release and lactotroph proliferation. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[32]  V. Murthy,et al.  Molecular Organization of Vomeronasal Chemoreception , 2011, Nature.

[33]  W. Young,et al.  Vasopressin: Behavioral roles of an “original” neuropeptide , 2008, Progress in Neurobiology.

[34]  S. Segovia,et al.  Sexual dimorphism in the vomeronasal pathway and sex differences in reproductive behaviors , 1993, Brain Research Reviews.

[35]  G. Calamandrei,et al.  Differential expression of Fos protein in the brain of female mice dependent on pup sensory cues and maternal experience. , 1994, Behavioral neuroscience.

[36]  C. Dulac,et al.  A functional circuit underlying male sexual behaviour in the female mouse brain , 2007, Nature.

[37]  Karl Deisseroth,et al.  Optogenetics in Neural Systems , 2011, Neuron.

[38]  E. Valenstein,et al.  Sexual Receptivity: Facilitation by Medial Preoptic Lesions in Female Rats , 1972, Science.

[39]  Philippe Soriano.  The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites. , 1997, Development.

[40]  I. Mechenthaler,et al.  Galanin – 25 years with a multitalented neuropeptide , 2008, Cellular and Molecular Life Sciences.

[41]  J. Mennella,et al.  Infanticide in the male rat: The role of the vomeronasal organ , 1988, Physiology & Behavior.

[42]  M. Numan,et al.  Medial preoptic area interactions with dopamine neural systems in the control of the onset and maintenance of maternal behavior in rats , 2009, Frontiers in Neuroendocrinology.

[43]  H. Bengtsson,et al.  Transgenic expression of Cre recombinase from the tyrosine hydroxylase locus , 2004, Genesis.

[44]  P. Kelly,et al.  Printed in U.S.A. Copyright © 1998 by The Endocrine Society Null Mutation of the Prolactin Receptor Gene Produces a Defect in Maternal Behavior , 2022 .

[45]  Richard E. Brown,et al.  Hormonal and experiential factors influencing parental behaviour in male rodents: An integrative approach , 1993, Behavioural Processes.

[46]  D. Corey,et al.  TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[47]  B. Trainor,et al.  Testosterone, Paternal Behavior, and Aggression in the Monogamous California Mouse (Peromyscus californicus) , 2001, Hormones and Behavior.

[48]  Y. Yoshihara,et al.  Behavioral Transition from Attack to Parenting in Male Mice: A Crucial Role of the Vomeronasal System , 2013, The Journal of Neuroscience.

[49]  F. V. vom Saal,et al.  The regulation of infanticide and parental behavior: implications for reproductive success in male mice. , 1982, Science.

[50]  M. Numan,et al.  Medial preoptic area and maternal behavior in the female rat. , 1974, Journal of comparative and physiological psychology.

[51]  G. J. Vries,et al.  Sex differences in the parental behavior of rodents , 2000, Neuroscience & Biobehavioral Reviews.

[52]  David J. Anderson,et al.  Functional identification of an aggression locus in the mouse hypothalamus , 2010, Nature.

[53]  M. McKinley,et al.  Multiple thermoregulatory effectors with independent central controls , 2010, European Journal of Applied Physiology.

[54]  T. Insel,et al.  The Neurobiology of Parental Behavior , 2003, Hormones, Brain, and Behavior.

[55]  J. Labov.  Factors influencing infanticidal behavior in wild male house mice (Mus musculus) , 1980, Behavioral Ecology and Sociobiology.

[56]  N. Shah,et al.  Sexually Dimorphic Neurons in the Ventromedial Hypothalamus Govern Mating in Both Sexes and Aggression in Males , 2013, Cell.

[57]  E. Hull,et al.  Dopamine, the medial preoptic area, and male sexual behavior , 2005, Physiology & Behavior.

[58]  Allan R. Jones,et al.  Genome-wide atlas of gene expression in the adult mouse brain , 2007, Nature.

[59]  Adele L. DeNicola,et al.  The importance of the basolateral/basomedial amygdala for goal-directed maternal responses in postpartum rats , 2010, Behavioural Brain Research.