TSSG turns to ICT in Neuroscience

Wireless Optogenetics Nanonetworks

Innovative treatments for many neurodegenerative diseases frequently involve the use of long-term implants able to monitor and stimulate different regions of the human brain. Such Brain Machine Interfaces (BMI) can generally be classified in two categories, namely, electrical BMIs and optical BMIs. The former rely on implanting electrodes into the skull to stimulate specific areas of the brain, such as the technique used to eliminate the shaking effects for patients suffering from Parkinson’s disease. The latter involves the use of light to stimulate individual or small sets of genetically engineered neurons—a concept known as optogenetics. Although the original design of optogenetic BMIs required optical fibers to be inserted into the skull, tremendous advancements have been made since towards wireless units that can be implanted into the cortex. Unfortunately, the majority of solutions have yet to address the challenges related to long-term applications. These include, among others, (i) the miniaturization of the optogenomic mote (i.e., light-source, controller and battery) to enable single neuron level stimulation, and (ii) the development of energy-harvesting systems to ensure everlasting operation. While the neural dust referenced in satisfies the miniaturization at the micrometer scale, the devices are currently focused on monitoring rather than stimulation. The wireless optogenetic device proposed in utilizes radio-frequency power source for charging the device. However, the size of unit is still currently at the millimeter scale. The concept of optogenetic neural dust has been recently proposed to realize the challenges addressed above. The proposed architecture extends the neural dust model and architecture proposed in , but includes the required optical source to stimulate the neurons. These devices can be scattered into the brain, more specifically into the micro neuronal network that compose the circuitry of the cortex. This can create an opportunity to achieve neuronal stimulation of specific neurons in the cortex . We recently have demonstrated in , that the successful stimulation of these devices inserted inside a cortical microcircuit can achieve regeneration of neuronal spike activity that was previously know. This open the doors for the design of future and incredibly precise brain-machine interfaces accompanied with more efficient methods for deep brain stimulation.
 

Figure 1- Wireless Optogenetics Nanonetworks is an attempt to achieve deep brain stimulation of neurons though nano-scale machines that perform light stimulation of neurons. This network is shown efficient to replicate known firing activity into a cortical microcircuit .

Control of Neuronal and Non-Neuronal Cells Towards Neurodegeneration Treatement
Approximately 24 million people worldwide suffer from dementia, of which 60% is due to Alzheimer’s disease . Alzheimer’s is the sixth leading cause of death for all ages and the fifth leading cause of death for those 65 years of age and older, with an annual cost of approximately $226 billion in the U.S. alone. But its treatment remains with symptom-preventing drugs that neglect the diseases progression or do not cure the disease. The blood-brain barrier also prevents the effectiveness of current Alzheimer’s drugs, blocking the flow of drug molecules to the brain by the central nervous system. Researchers have found that nanoparticles can potentially bypass the blood-brain barrier. Therefore, nanotechnology alongside with biotechnology is an exciting approach that not only provides new drugs and treatments to Alzheimer’s, but can also enable a cure for the disease. Alzheimer’s main cause is the lack of glutamate in the tripartite synapses (three way molecular communication between neurons and astrocytes), which leads to poor synaptic transmission and therefore lack of memory, bad sleep, depression, and so on. The control of the concentration of glutamate can therefore increase the synaptic quality, providing a new and potentially more efficient way to treat Alzheimer’s.
Since, glutamate release is controlled by the intracellular Ca2+ signalling in the astrocytes of the tripartite synapses, providing desired levels of Ca2+ can result in the desired regulation of glutamate. The goal of this research is to investigate a potential way of obtaining such an outcome. We use the feed-forward feedback control theory, combined with communication theory and synthetic biology, to regulate the internal Ca2+ signalling of astrocytes in the tripartite synapses, providing sufficient levels of glutamate to control the quality of the synaptic transmission . This is not only applicable to Alzheimer’s but also to other neurodegenerative diseases, because it enables a new way of maintaining the stability and health of the brain tissues using nanotechnology and engineering principles. We believe that such a control system can be implemented using the previous technology, the wireless optogenetics nanonetworks. This interdisciplinary approach will cause a significant impact on biotechnology, nanotechnology, Alzheimer’s disease and drug delivery system research fields with also an important economic potential effect .

 Figure 2 The feed-forward feedback control of neuronal and non-neuronal cells activity for possible neurodegeneration treatment. By controlling the ca2+ regulation in astrocyte we intend to achieve the control of the amount of glutamate in the synaptic channel.

Acknowledgement
This work is funded by the Irish Research Council under the grant GOIPD/2016/650.
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