Pablo Chamero

Research

Goals

Our goal is to define molecular, cellular and endocrine mechanisms that control complex mammalian behavior such as aggression, avoidance, mating and kin recognition. We study how semiochemicals such as pheromones, kairomones and other olfactory social signals, and their detection by the mammalian olfactory system enables appropriate social interactions. We use mouse molecular genetic tools, electrophysiological, calcium imaging, neuronatomy and behavioral analysis to address which neuronal circuits activate social behavior.

Background

In most mammal species, social behaviors are initiated in the olfactory system by the detection of specific olfactory signals. Small organic molecules, peptides, and proteins that serve as semiochemicals have been identified from secretions of conspecifics or predators. These signals are mainly detected by chemosensory neurons of the vomeronasal organ (VNO), an olfactory sub-system located in the nose. In the VNO, are present at least two populations of receptor cells that detect pheromones through two families of G-protein-coupled receptors (GPCRs), V1Rs and V2Rs. The binding of pheromone ligands to the receptor (V1R or V2R) has been suggested to activate the corresponding G protein (Gαi2 and Gαo respectively) which in turn will stimulate a phospholipase C. This activity triggers the production of the second messenger diacylglycerol (DAG) that gates a TRPC2 ion channel.
A major issue in pheromone communication is to associate pheromone ligands with their receptors and determine the corresponding behavior. Every VNO sensory neuron is thought to be defined by the expression of one single receptor of the whole V1R and V2R repertoire. There are about 300 genes encoding for pheromone V1R and V2R receptors in the mouse genome and only few of them have been matched to any potential ligand. The difficulty in detecting neural responses in VNO neurons lies in the fact that they represent a highly heterogeneous group with respect to the receptors they express, presumably causing heterogeneous ligand specificity as well.

Strategy

We aim to characterize the molecular, cellular and endocrine mechanisms that control the olfactory-mediated social behaviors. The novel strategy in these studies will be to identify a G protein-coupled receptor (GPCR) and the associated neuronal pathways by using known ligands which are linked to a specific behavior.
It is still subject to controversy how pheromones encode for aggression and other behaviors in mice. To address this, we are identifying 1) the nature of specific pheromones is and how they are detected. 2) Expand the molecular characterization to identify the specific receptors that recognize the aggression-promoting pheromones. 3) The precise roles that each of the olfactory subsystems within the nose play in behavior. 4) How gender and sex hormones regulate behavior and understand how behavioral dimorphic differences in general are processed in the central nervous system. 5) Address the logic of the circuitry underlying behavior through the neural pathways of the pheromone detecting neurons. Analysis of these parameters enable to determine principles that specify social stereotyped behaviors and the neural mechanisms that control them.

Techniques

Live cell calcium imaging: high resolution Ca2+ imaging in free-moving mice (microendoscopic), dissociated cells, and living tissue slices.
In vivo genetic models: gene deficient mouse lines (knockout) and genetically labeled transgenic mouse models.
Behavioral assays: resident-intruder assay, maternal aggression, odorant discrimination, etc.
Molecular biology: single cell PCR, molecular cloning, transfection, gene targeting by homologous recombination, etc.
Virus-based gene transfer: Herpes simplex virus, adenovirus, AAV, lentivirus.
Histology: immunohistochemistry, neuroanatomy, in situ hybridization and confocal microscopy.

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