Cell-specific expression of mGluRs in amygdala

The recent availability of the human and mouse genome sequences has been a first step in a new way to address biological questions related to gene function in health and disease. The mechanisms that regulate cell-specific expression of a gene and how gene expression responds to changes in the environment can now be explored. In the brain, this knowledge is particularly important since transcriptionalranslational regulation of receptor proteins, such as those for the excitatory neurotransmitter glutamate, can influence dramatically the excitability, plasticity and output of neuronal networks. We are particularly interested in a family of glutamate receptors, known as metabotropic glutamate receptors (mGluRs), which through their coupling to G-proteins trigger elaborated intracellular events at the basis of complex functions/behaviours that include learning, memory and possibly emotions. A pivotal role for these functions is played by the amygdaloid complex. This research project aims at elucidating the exact location of mGluRs, at the synaptic level, in the amydgala in relation to both the different cellular constituents and the relevant intrinsic and extrinsic amygdaloid connections. These studies will provide the necessary anatomical background for the assessment of mGluR cell-specific expression and a window on the organisational principles of distinct synaptic and cellular interactions within the amygdala. To understand how the expression of mGluRs is spatially, temporally and quantitatively regulated, the complete genomic structure of these genes will be delineated including the identification of the core promoter regions and of the cis and trans- regulatory elements. In order to complement the understanding of the integrative mechanisms involved in the processing of information in the amygdala some of the basic physiological, pharmacological and anatomical properties of distinct neuronal ensemble will be also investigated. The role of glutamatergic neurotransmission involving mGluRs in the amygdala in processes relevant to emotion and social behaviour may reveal a new opportunity for the development of novel pharmacological approaches to treating neuropsychiatric disorders such as autism, depression, schizophrenia, and anxiety.