It is known that the neurons of the human brain communicate with each other through specialized structures called synapses. A synapse consists of a presynaptic terminal of one neuron and a postsynaptic terminal of another. The presynaptic terminal stores vesicles containing neurotransmitters, while the postsynaptic terminal contains neurotransmitter receptors. The amount and coordinated release of neurotransmitters regulates synaptic strength which is critical to maintain proper communication between neurons.
A dense collection of proteins is present in these terminals, however the functional role of many of these proteins remains unknown. Now, a study from researchers at the Max Planck Florida Institute has shown for the first time that GIT proteins are critical presynaptic regulators of synaptic strength. The team state that this regulation is likely to contribute to the disruptions in neural circuit functions leading to sensory disorders, memory and learning impairment and other neurological disorders. The opensource study is published in the journal Neuron.
Previous studies show that the G-protein-coupled receptor kinase-interacting proteins (GITs) exert a critical control in synaptic transmission, since deletions of these proteins are lethal or cause sensory deficits and cognitive impairments in mice. In particular, GIT proteins and the pathways they regulate have been implicated in neurological disorders such as Attention Deficit Hyperactivity Disorder (ADHD) and Huntington’s Disease. Several studies have demonstrated the role of GITs in the postsynaptic terminal, but very little is known about their role in the presynaptic terminal. The lab set out to investigate the role of GITs in the giant synapse, the calyx of Held, of the auditory system, the optimal model to study the presynaptic terminal independently from the postsynaptic terminal. The current study shows previously unknown roles for GIT1 and GIT2 in regulating neurotransmitter release strength, with GIT1 as a specific regulator of presynaptic release probability.
The current study shows that presynaptic deletion of the GIT1 and GIT2 proteins at the mouse calyx of Held leads to a large increase in action potential release with no change in the readily releasable pool size. Results show that selective presynaptic GIT1 ablation identified a GIT1-specific role in regulating release that was largely responsible for increased synaptic strength. Data findings show that increased synaptic strength was not due to changes in voltage-gated calcium channel currents or activation kinetics.
The team surmise that their findings reveal an important function of a class of presynaptic proteins previously implicated in neurological disorders in the regulation of synaptic strength. For the future, the researchers state they plan to resolve the mechanisms by which GITs regulate synaptic strength and their roles in the early stages of auditory processing and neurological diseases.
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