in glutamatergic neuronal cells. SNAP-25 leads to a reduction of current density through VGCC's and therefore a decrease in the amount of calcium that is binding the synaptotagmin, causing a decrease in neuronal glutamatergic exocytosis. Conversely, underexpression of SNAP-25 allows for an increase in VGCC current density and increase in exocytosis. Further investigation has suggested possible relationships between SNAP-25 over/underexpression and a variety of brain diseases. In attention-deficit/hyperactivity disorder or ADHD, polymorphisms at the SNAP-25 gene locus in humans have been linked to the disease suggesting a potential role in its manifestation. This is further suggested by heterogeneous SNAP-25 knockout studies performed on coloboma mutant mice, which led to phenotypic characteristics of ADHD. Studies have also shown a correlation of SNAP-25 over/underexpression and the onset of schizophrenia. Syntaxin and the Habc domain Syntaxin consists of a transmembrane domain (TMD), alpha-helical SNARE domain, a short linker region, and the Habc domain which consists of three alpha-helical regions. The SNARE domain in syntaxin serves as a target site for docking of SNAP-25 and synaptobrevin in order to form the four helix bundle requisite to the SNARE complex and subsequent fusion. The Habc domain, however, serves as an autoinhibitory domain in syntaxin. It has been shown to fold over and associate with the SNARE domain of syntaxin inducing a "closed" state, creating a physical barrier to the formation of the SNARE motif. Conversely, the Habc domain can again disassociate with the SNARE domain leaving syntaxin free to associate with both SNAP-25 and synaptobrevin. Syntaxin 1B and readily releasable pool of vesicles There is an immense diversity of syntaxin subtypes, with 15 varieties in the human genome. It has been suggested that syntaxin1B has a role in regulating number of synaptic vesicles ready for exocytosis in the axon terminal. This is also called the readily releasable pool (RRP) of vesicles. A knock out study in 2014 showed that the lack of syntaxin1B led to a significant decrease in RRP size. Toxins Many neurotoxins directly affect SNARE complexes. Such toxins as the botulinum and tetanus toxins work by targeting the SNARE components. These toxins prevent proper vesicle recycling and result in poor muscle control, spasms, paralysis, and even death. Botulinum neurotoxin Botulinum Toxin (BoNT) is one of the most potent toxins to have ever been discovered. It is a proteolytic enzyme that cleaves SNARE proteins in neurons. Its protein structure is composed of two peptide