Award details

MHC peptide ligands and the recognition of chemosensory individuality in mice

Reference	BB/C005015/1
Principal Investigator / Supervisor	Dr Peter Brennan
Co-Investigators / Co-Supervisors
Institution	University of Bristol
Department	Physiology and Pharmacology
Funding type	Research
Value (£)	265,582
Status	Completed
Type	Research Grant
Start date	01/11/2005
End date	31/10/2008
Duration	36 months

Abstract

Rodents produce chemical signals in their body secretions and urine that convey information about the individual identity of the producer, and have important influences on their behaviour. Recent advances have led to the identification of a novel class of ligands for vomeronasal sensory receptors that are associated with the major histocompatibility complex (MHC) genotype, and which form a direct link between the recognition of individuality at the immunological and behavioural levels. These novel chemosignals are nine amino acid peptide ligands of the MHC class 1 proteins. They convey information about the individuality of the producer by virtue of the conformation of large hydrophobic anchor residues, which determine the specificity of their binding by the MHC class 1 proteins, and their activation of vomeronasal sensory neurons. Moreover, my group has shown that the signal strain identity in the pregnancy block effect that enables a female mouse to recognise the urinary chemosignals of her mate. This project will investigate whether application of synthetic peptides can convey information about strain identity in other behavioural contexts that are influenced by MHC genotype, such as mate choice and parent offspring interactions. We will also examine the behavioural effects of these peptides in mice that have been cross-fostered at birth to establish the extent to which the responses to these peptides are innate or learned. The main olfactory system is specialised for the detection of volatile, airborne odourants, wherease the vomeronasal system is specialised for detecting relatively non-volatile chemosignals by direct contact with the source. Both of these systems convey information about individuality, which is integrated along with other sensory information by the medial amygdala. A further aim of the proposed research is to investigate the complimentary roles of these two chemosensory systems in conveying information about strain identity that influences mate choice and mother-infant interactions. This will be achieved by investigating potential deficits in these behaviours in genetically manipulated mice such as the trp2 knockout line, which lacks functional vomeronasal sensory neurons, or the OMPntr line in which specific ablations of the main olfactory sensory neurons can be induced. Finally, a major objective of this research is to investigate the electrophysiological responses of neurons in the medial amygdala to strain specific chemosignals such as the MHC peptides. We are particularly interested in whether individual neurons in the medial amygdala respond to individuality information sensed by both the main olfactory and vomeronasal systems, and how the integration of this information is affected in animals with specific dysfunction of either system. These investigations open up a new field of research into the role of peptides as individually signals and will increase our understanding of the complimentary roles played by the main and vomeronasal systems in mediating chemosensory influences on mouse behaviour.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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