Synaptic Genes and Proteins
SynGO allows you to search a database of genes and proteins which are enriched in the synapse. Its content is structured by evidence manually inspected and curated by experts in synapse biology. It also includes cell type and developmental expression heatmaps.
Several genes encoding synaptic submodules are conserved across vertebrates, mollusks and nonbilaterians. In the sponge Amphimedon queenslandica, these genes mediate chemo- and photo-sensing systems underlying larval settlement behaviors.
Pre-synaptic
Synaptic function reflects the complex interplay between pre- and postsynaptic components. Maturation of excitatory and GABAergic synapses requires a full complement of pre-synaptic proteins, including the SNAREs synaptotagmins and synapsins, the scaffold proteins PSD95 and SAP102, and AMPA-type glutamate receptors for excitation and inhibitory postsynaptic neurons respectively [1].
Gene expression patterns at individual synapses vary across cell types or layers. Using WGCNA and hierarchical clustering, we identified gene modules that have highest variance within specific cell classes or layer (discrete modules) and those with a gradient of expression across all cells in a given class or layer (intermediate or pure gradients).
Among these modules are genes that regulate synaptic vesicle trafficking at the pre-synaptic terminal. For example, synapsin is required for a reserve pool of SVs that is readily releasable upon stimulation. Its activation is regulated by Syn site-specific phosphorylation that alters its interaction with SVs and the actin cytoskeleton and changes the availability of its C-terminal domain, which modulates its association with the PdBu sensitive vesicle pool and PHP.
Post-synaptic
The formation of synapses depends on interactions between pre- and post-synaptic neurons, but other cells in the same vicinity also influence synapse development. Guidepost cells, for example, are intermediate targets for axon guidance events and can shape synapse formation by acting as positive or negative regulators.
A new technology for selectively delivering genes into pre- or post-synaptic local interneurons in neocortical cortex is based on synthetic peptide neurotransmitter delivery. The N-terminal domain of the recombinant protein contains a DCV sorting domain; the middle domain binds to GABAA receptors; and the C-terminus is tagged with His. This recombinant protein is expressed in presynaptic neurons and upon release binds to GABAA receptors in postsynaptic neurons that express the cognate receptor, thereby selectively targeting them for gene transfer.
The resulting gene transfer is efficient in pre-synaptic neurons and postsynaptic dendrites expressing the targeted receptor. However, other proximal postsynaptic neurons that express the receptor but do not receive a synapse from a transduced presynaptic neuron and do not express the selected GABAergic subtype marker do not get transduced.
Scaffolding
Scaffolding is a learning technique that provides support for students as they master new skills. It allows teachers to move away from a more directive role and fosters student self-regulation. It takes time and planning, however. Teachers need to assess their students’ prior knowledge and monitor progress to determine what level of support is needed. This requires a good understanding of children’s overall development and their unique communication and learning styles.
The synapse-building protein Nrxn binds to its postsynaptic partner Nlgn and promotes synaptic assembly, maturation, and plasticity. Mutations in the autism spectrum disorder (ASD)-associated gene Pten disrupt this pathway, leading to abnormalities in synapse formation, synapse elimination, and synaptic transmission.
Another important scaffolding gene is Munc18-1, a protein that regulates synaptic activity and function. Mutations in this gene cause a variety of neurological disorders, including autism and intellectual disability. In addition to regulating presynaptic release, Munc18-1 controls the phosphorylation of GABAARs in the hippocampus, which affects iLTP and long-term depression (LTD). This mechanism is also implicated in ASD-associated cognitive deficits.
Pruning
Scientists are now analyzing whether the same pruning mechanisms that help refine brain wiring early in life may contribute to pathological synapse loss seen in neurodegenerative disorders. If so, this may offer a target for therapy.
From conception until about 2 years old neurons and synapses grow at an incredible rate. But by that time, they’ve built far more connections than they’ll ever functionally need. So a brain-wide pruning process kicks in. It is not unlike a gardener removing overgrown branches or a sculptor chiseling and molding stone into a statue. Victorious connections strengthen and widen, while unsuccessful ones weaken and fade in a process known as apoptosis.
This pruning takes place while you sleep, when the brain is less preoccupied with external stimuli. It’s a good thing, too, because previous studies have shown that people with mental health problems have fewer neural connections in the frontal cortex, which is involved in critical thinking and decision making.