@article {69171,
	title = {Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome.},
	journal = {Neuron},
	year = {2024},
	month = {2024 Jan 24},
	abstract = {<p>Neurons express various combinations of neurotransmitter receptor (NR) subunits and receive inputs from multiple neuron types expressing different neurotransmitters. Localizing NR subunits to specific synaptic inputs has been challenging. Here, we use epitope-tagged endogenous NR subunits, expansion light-sheet microscopy, and electron microscopy (EM) connectomics to molecularly characterize synapses in Drosophila. We show that in directionally selective motion-sensitive neurons, different multiple NRs elaborated a highly stereotyped molecular topography with NR localized to specific domains receiving cell-type-specific inputs. Developmental studies suggested that NRs or complexes of them with other membrane proteins determine patterns of synaptic inputs. In support of this model, we identify a transmembrane protein selectively associated with a subset of spatially restricted synapses and demonstrate its requirement for synapse formation through genetic analysis. We propose that mechanisms that regulate the precise spatial distribution of NRs provide a molecular cartography specifying the patterns of synaptic connections onto dendrites.</p>
},
	issn = {1097-4199},
	doi = {10.1016/j.neuron.2023.12.014},
	author = {Sanfilippo, Piero and Kim, Alexander J and Bhukel, Anuradha and Yoo, Juyoun and Mirshahidi, Pegah S and Pandey, Vijaya and Bevir, Harry and Yuen, Ashley and Mirshahidi, Parmis S and Guo, Peiyi and Li, Hong-Sheng and Wohlschlegel, James A and Aso, Yoshinori and Zipursky, S Lawrence}
}
@article {68964,
	title = {Brain wiring determinants uncovered by integrating connectomes and transcriptomes.},
	journal = {Current Biology},
	volume = {33},
	year = {2023},
	month = {2023 Aug 23},
	pages = {3998-3998},
	abstract = {<p>Advances in brain connectomics have demonstrated the extraordinary complexity of neural circuits. Developing neurons encounter the axons and dendrites of many different neuron types and form synapses with only a subset of them. During circuit assembly, neurons express cell-type-specific repertoires comprising many cell adhesion molecules (CAMs) that can mediate interactions between developing neurites. Many CAM families have been shown to contribute to brain wiring in different ways. It has been challenging, however, to identify receptor-ligand pairs directly matching neurons with their synaptic targets. Here, we integrated the synapse-level connectome of the neural circuit with the developmental expression patterns and binding specificities of CAMs on pre- and postsynaptic neurons in the Drosophila visual system. To overcome the complexity of neural circuits, we focus on pairs of genetically related neurons that make differential wiring choices. In the motion detection circuit, closely related subtypes of T4/T5 neurons choose between alternative synaptic targets in adjacent layers of neuropil. This choice correlates with the matching expression in synaptic partners of different receptor-ligand pairs of the Beat and Side families of CAMs. Genetic analysis demonstrated that presynaptic Side-II and postsynaptic Beat-VI restrict synaptic partners to the same layer. Removal of this receptor-ligand pair disrupts layers and leads to inappropriate targeting of presynaptic sites and postsynaptic dendrites. We propose that different Side/Beat receptor-ligand pairs collaborate with other recognition molecules to determine wiring specificities in the fly brain. Combining transcriptomes, connectomes, and protein interactome maps allow unbiased identification of determinants of brain wiring.</p>
},
	issn = {1879-0445},
	doi = {10.1016/j.cub.2023.08.020},
	author = {Yoo, Juyoun and Dombrovski, Mark and Mirshahidi, Parmis and Nern, Aljoscha and LoCascio, Samuel A and Zipursky, S Lawrence and Kurmangaliyev, Yerbol Z}
}
