Gene Expression of Caenorhabditis elegans Neurons Carries Information on Their Synaptic Connectivity

Abstract

The claim that genetic properties of neurons significantly influence their synaptic network structure is a common notion in neuroscience. The nematode Caenorhabditis elegans provides an exciting opportunity to approach this question in a large-scale quantitative manner. Its synaptic connectivity network has been identified, and, combined with cellular studies, we currently have characteristic connectivity and gene expression signatures for most of its neurons. By using two complementary analysis assays we show that the expression signature of a neuron carries significant information about its synaptic connectivity signature, and identify a list of putative genes predicting neural connectivity. The current study rigorously quantifies the relation between gene expression and synaptic connectivity signatures in the C. elegans nervous system and identifies subsets of neurons where this relation is highly marked. The results presented and the genes identified provide a promising starting point for further, more detailed computational and experimental investigations.

A transcriptional signature of hub connectivity in the mouse connectome

“…For both reciprocal and unidirectional connections, correlated gene expression is driven by the same types of functional gene groups, pointing to a uniform transcriptional profile of connectivity that increases with connection reciprocity. Similar functional categories of genes related to the development of neurons, neurites, and synapses, as well as the regulation of neuronal activity and synaptic plasticity, contribute to predicting the presence of a connection between neurons in Caenorhabditis elegans (15,16) and larger-scale neuronal populations of the rat (17) and mouse brains (18,19). The consistency of these findings across species, datasets, and analysis methods points to a robust transcriptional signature of neuronal connectivity characterized by the coordinated expression of genes involved in the development and ongoing function of neuronal networks.…”

“…This conservation suggests that hub connectivity may be under tight genetic control. Growing evidence indicates that gene expression affects neuronal connectivity, with studies of worm, rat, and mouse nervous systems showing that the transcriptional profile of an individual neuron or neuronal population can predict its connectivity to other areas with greater than chance accuracy (15)(16)(17)(18)(19). Brain regions with similar transcriptional profiles display similar connectivity profiles (20,21), and gene expression profiles are more correlated between pairs of structurally connected brain regions in the mouse/rat (20) and within functionally coupled networks of the human cortex (22).…”

Coupling of gene expression in medial prefrontal cortex and nucleus accumbens after neonatal ventral hippocampal lesions accompanies deficits in sensorimotor gating and auditory processing in rats

“…Flores et al 2009) have used gene expression patterns across brain regions as a means to understand the role of circuit dynamics in the regulation of behaviors – such as PPI – that are of relevance to schizophrenia; this strategy is based in part on emerging evidence that correlated gene expression levels predict anatomical connectivity between brain regions (Kaufman et al 2006; Wolf et al 2011). We reported significant differences in the cortical (mPFC), subcortical (nucleus accumbens; NAC) and ventral hippocampal (VH) expression of Comt, Grid2, Nrg1 and other genes associated with PPI deficits in schizophrenia patients (Greenwood et al 2011, 2012; Kao et al 2010; Quednow et al 2010; Roussos et al 2008; Sobin et al 2005; Stefansson et al 2002) in outbred Sprague Dawley (SD) vs. Long Evans (LE) rat strains that also differed in PPI and PPI-sensitivity to dopamine agonists (Shilling et al 2008; Swerdlow et al 2012b).…”

Allen mouse brain atlases reveal different neural connection and gene expression patterns in cerebellum gyri and sulci

“…The names of gyri are the abbreviation of structure names based on the brain ontology, and the names of sulci are given by joining the two abbreviations of structure names, since its voxels belong to two structures. The names of sulci with 'SU' after '-' denote that they belong to only one brain structure small number of genes usually contribute to the generation of neuronal connectivity (Kaufman et al 2006). …”