The functional role of a receptor and an ion channel depends on its intrinsic properties and its location on the neuronal surface. The classical view on the subcellular distribution of receptors and ion channels is that they are present either in axons or in the somato-dendritic domain. The working hypothesis of our laboratory is that neurotransmitter receptors and ion channels are selectively associated with specific synaptic inputs or specific subcellular compartments. Because the majority of synaptic inputs arrive on the dendrites, the dendritically located neurotransmitter receptors and ion channels are placed in a strategic position to influence the integration of the incoming synaptic inputs. However, if an ion channel is present throughout the entire dendritic tree, it will have an effect on all synaptic inputs. An attractive idea to increase further the computational power of single neurons is that a given ion channel might be selectively associated with a specific subcellular compartments and/or synaptic input. We will use high-resolution, highly sensitive immunogold localization techniques (pre-embedding immunogold and SDS-FRL) to demonstrate synapse-specific association of neurotransmitter receptors and ion channels, as well as their cell surface distribution patterns along the entire neuron.
Subcelular localization of GABAB1 in Purkinje cells of the cerebellum using the SDS-FRL technique. Clusters of immunoparticles are observed at the P-face of dendritic shafts (Den) and spines (s). Scale bar: 500 nm.
Ballesteros-Merino C, Watanabe M, Shigemoto R, Fukazawa Y, Adelman JP, Luján R (2014) Differential subcellular localization of SK3 channels in the hippocampus. European Journal of Neuroscience 39(6):883-92.
Martínez-Hernández J, Ballesteros-Merino C, Fernandez-Alacid L, Nicolau JC, Luján R (2012) Polarized localization of the voltage-gated sodium channel Nav1.2 in cerebellar granule cells. Cerebellum 12(1):16-26.
Ferrandiz-Huertas C, Gil-Minguez M, Luján R (2012) Regional expression and subcellular localization of the β subunits of voltage-gated calcium channels in the developing brain. Journal of Neurochemistry 122(6):1095-107.
Deignan J, Luján R, Bond C, Riegel A, Watanabe M, Williams JT, Maylie J, Adelman JP (2012) SK2 and SK3 expression differentially affect firing frequency and precision in dopamine neurons. Neuroscience 217:67-76.
Fernández-Alacid L, Watanabe M, Molnár E, Wickman K, Luján R. (2011) Developmental regulation of G protein-gated inwardly-rectifying K+ (GIRK/Kir3) channel subunits in the brain. European Journal of Neuroscience 34(11):1724-36.
Ballesteros-Merino C, Lin M, Wu WW, Ferrándiz-Huertas C, Cabañero MJ, Watanabe M, Fukazawa Y, Shigemoto R, Maylie J, Adelman JP, Luján R. (2012) Developmental profile of SK2 channel expression and function in CA1 neurons. Hippocampus 22(6):1467-80.
Allen D*, Bond CT*, Luján R*, Ballesteros-Merino C, Lin MT, Wang K, Klett N, Watanabe M, Shigemoto R, Stackman RW Jr, Maylie J, Adelman JP. (2011) The SK2-long isoform directs synaptic localization and function of SK2-containing channels. Nature Neuroscience 14(6):744-749.
Fernández-Alacid L, Aguado C, Ciruela F, Martín R, Colón J, Cabañero MJ, Gassmann M, Watanabe M, Shigemoto R, Wickman K, Bettler B, Sánchez-Prieto J, Luján R (2009) Subcellular compartment-specific molecular diversity of pre- and postsynaptic GABA(B)-activated GIRK channels in Purkinje cells. Journal of Neurochemistry 110(4):1363-76.