Dr. Tali Kimchi

Office: Arison building, room #208

Department of Neurobiology

Weizmann Institute of Science

Rehovot 76100, Israel

Tel: +972-8-934-6216

FAX: +972-8-934-6357
Email: tali.kimchi@weizmann.ac.il

 

 

 

 

 

Research Subject:

Neuronal and molecular mechanisms of sexually dimorphic social and reproductive responses in mammals.

 

Research Background:

From invertebrates to humans, males and females of a given species display identifiable differences in behaviors, mostly but not exclusively pertaining to sexual and social behaviors, which is crucial to the reproductive success of the animal and the survival of the species. A long-standing and fundamental neurobiological question is ‘how are sex-specific behaviors, such as courtship, mating, nursing, and aggression encoded by neural circuits?’ These dimorphic behaviors include a robust set of species-specific fixed action patterns that can be elicited in socially naïve animals, suggesting that the underlying neuronal substrates necessary for their execution are likely to be genetically determined and developmentally programmed.

Surprisingly, with few exceptions, the quest for traces of fundamental differences in male and female mammalian brain structures and circuits that would parallel those of sexual behaviors and peripheral organs has so far uncovered modest quantitative differences rather than clear qualitative differences as expected.

 

How do sex differences in behavior arise? What are the molecules and neural circuits govern sexually dimorphic innate behaviors such as mating, aggression and care of young? How do sensory and social stimuli modulate innate sexually dimorphic responses?

 

In most mammals, the vomeronasal organ (VNO) is a primary chemosensory organ that detects pheromonal signals in the environment. Pheromones, present in urine and different exocrine gland secretions, provide information about an individual’s social and reproductive status and can elicit innate immediate behavioral responses along with long-lasting neuroendocrine responses.

 

Genetic ablation of the gene encoding TRPC2, an ion channel essential for VNO signaling, has provided a robust experimental system to directly investigate the repertoire of VNO-mediated sensory responses and behaviors. It was shown that the TRPC2-/- male mutants exhibit profound defects in male-male aggression and in their ability to distinguish between males and females, and displayed mating behavior toward males and females with equal frequency.

Recently we discovered that TRPC2-/- females display a loss of sex discrimination and a reduction in female-specific behaviors, which include maternal aggression and lactating behavior. Remarkably, mutant females also adopting a male-typical pattern of mating behaviors including mounting, pelvic thrust, anogenital olfactory investigation, and emission of complex ultrasonic vocalizations (video).

 

These findings suggest a new model in which male and female mating circuits exist in both sexes, but sex-specific chemosensory circuitry directs pheromonal cues to brain circuitry that activates same sex circuitry and represses opposite sex behavior circuitry thus allowing for the initiation of the appropriate male or female behavior


Research Interests:

         Sexually dimorphic pheromone signals – perception, processing and biology function.

         Characterizing novel pheromone-mediated behavioral and neuroendocrine responses in wild-caught mouse colonies.

         Identifying the genetic basis of sex-typical social and reproductive behaviors.

         Mapping and manipulating brain circuits controlling reproductive behaviors in males and females.

 

Research Methodologies:

Behaviors: We are using innovative costume-designed experimental set-ups including, large semi-natural enclosures that are equipped with array of cameras, microphones and telemetry-based systems, to remotely record large battery of social interactions and physiology data, in naturally behaving mouse colonies.

Molecular and cellular: Genetic modified mouse lines and conditional viruses are used to manipulate gene expression, neuronal activities, and to trace neuronal circuits.

Large scale genetic profiling: Microarray and high-throughput sequencing Solexa (Illumina) platforms are used for large scale gene expression profiling in animals with normal and deviate sex-typical behavioral repertoires.

 

 

Selected Publications:

·       Kimchi, T. and Terkel, J. (2001). Spatial learning and memory in the blind mole rat (Spalax ehrenbergi) in comparison with the laboratory rat and Levant vole. Animal Behaviour, 61, 171-180. [PDF]

·       Kimchi, T. and Terkel, J. (2001). Magnetic compass orientation in the blind mole rat, Spalax ehrenbergi. Journal of Experimental Biology, 204, 751-758. [PDF]

·       Kimchi, T. and Terkel, J. (2002). Seeing and not seeing. Current Opinion in Neurobiology, 12, 728-734. [PDF]

·       Kimchi, T. and Terkel, J. (2003). Mole rats (Spalax ehrenbergi) select bypass burrowing strategies in accordance with obstacle size.
Naturwissenschaften, 90, 36-39. [PDF]

·       Kimchi, T. and Terkel, J. (2003). Detours by the blind mole-rat follow assessment of location and physical properties of underground obstacles. Animal Behaviour, 66, 885-891. [PDF]

·       Kimchi, T. Etienne, A. and Terkel, J. (2004). A subterranean mammal uses the magnetic orientation for path integration. Proc Natl Acad Sci USA, 101, 1105-1109. [PDF] [News and Views]

·       Kimchi, T. and Terkel, J. (2004). Comparison of the role of somatosensory stimuli in maze learning in a blind subterranean rodent and a sighted surface-dwelling rodent. Behavioural Brain Research, 153, 389-395. [PDF]

·       Kimchi, T., M. Resehf and Terkel, J. (2005). Evidence for the use of reflected self-generated seismic waves for spatial orientation in a blind subterranean mammal. Journal of Experimental Biology, 208, 647-659. [PDF] [JEB inside]

·       Dulac, C & Kimchi, T. (2007). Neural mechanisms underlying sex-specific behaviors in vertebrates. Current Opinion in Neurobiology, 17, 675-683 [PDF]

·       Kimchi, T., Jennings Xu and Dulac C. (2007). A functional circuit underlying male sexual behaviour in the female mouse brain.
Nature, 448, 1009-1013. [PDF] [News and Views] [Neuron Report] [Harvard Magazine Report] [Nature Review Neuroscience Report] [video1] [video2]