Neurons adjust their synapses by altering the synthesis of hundreds of proteins to regulate synaptic strength and network activity.
Learning and memory formation are based on our brain’s ability to adjust and regulate neuronal network activity. Neurons communicate at specialized structures known as synapses, and they are able to control the strength of their synaptic connections in response to changes in both the magnitude and frequency of inputs.
This process, “synaptic plasticity”, includes homeostatic scaling, a process by which neurons are able to stabilize network activity in response to large perturbations. Scientists at the Max Planck Institute for Brain Research in Frankfurt am Main now report a detailed analysis of the proteins synthesized by neurons to mediate homeostatic scaling.
Using bio-orthogonal labeling strategies, they discovered changes in newly-synthesized proteins, including known proteins involved in synaptic plasticity, but also new, yet uncharacterized proteins. The extensive, publicly-available dataset generated in this study provides a valuable starting point and reference for future studies of homeostatic scaling and has been published in the latest issue of Neuron.
Changes in the synthesis of cellular proteins lie at the heart of all adaptations that cells undergo. The complete complement of proteins expressed in a cell is known as the proteome. Tracking proteome changes in neurons during synaptic plasticity represents a major challenge: how can one distinguish the newly synthesized proteins from the pre-existing proteins within a cell?
This challenge was addressed by making use of bio-orthogonal, non-canonical amino acid tagging (BONCAT) - a method previously developed by Erin Schuman, Director at the Max Planck Institute for Brain Research in Frankfurt, and her colleagues Daniela Dieterich (Magdeburg) and Dave Tirrell (Caltech). In this technique, neurons incorporate artificial amino acids into new proteins, allowing subsequent visualization and purification of the newly-synthesized proteome produced upon stimulation or treatment.
Together with the joint proteomics lab of the Max Planck Institute for Brain Research and Max Planck Institute of Biophysics (headed by Julian Langer), 5940 newly-synthesized proteins were detected and analyzed in primary hippocampal neurons undergoing opposing forms of homeostatic plasticity. “We observed no significant changes in the overall number of proteins being synthesized, but rather adaptations to the expression levels of hundreds of proteins”, says Christoph Schanzenbächer, lead author of the manuscript.
The discovered proteins are involved in many important neuronal processes including neurite outgrowth, axon guidance, excitatory synapses, and glutamate receptor complexes. In addition, the majority of the differentially regulated proteins were directly associated with neurological diseases, including schizophrenia, epilepsy, and Parkinson’s disease – thus establishing a direct link between protein groups and disease models.
“We are particularly intrigued by the proteins previously not associated with neuronal learning, as these proteins may represent new, exciting candidates for future studies”, says Julian Langer. The full dataset has been made publicly available upon publication.
This study provides new, unprecedented insights into the proteomic response of primary neurons undergoing homeostatic, synaptic plasticity. In the future, the team in Frankfurt is working on transferring the technique to other systems. “An exciting next direction is the selective labeling of specific cell types in vivo and the direct tracking visualization and analysis of the associated proteomes” says Erin Schuman.
Publication: Schanzenbächer, C.T., Sambandan, S., Langer, J.D. and Schuman, E.M. (2016) Nascent Proteome Remodeling following Homeostatic Scaling at Hippocampal Synapses. Neuron 92(2): 358–371
Dr. Arjan Vink | Max-Planck-Institut für Hirnforschung
In focus: Peptides, the “little brothers and sisters” of proteins
12.11.2018 | Technische Universität Berlin
How to produce fluorescent nanoparticles for medical applications in a nuclear reactor
09.11.2018 | Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly
The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...
Scientists developed specially coated nanometer-sized vehicles that can be actively moved through dense tissue like the vitreous of the eye. So far, the transport of nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. The work was published in the journal Science Advances and constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.
Researchers of the “Micro, Nano and Molecular Systems” Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, together with an international...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
12.11.2018 | Life Sciences
12.11.2018 | Materials Sciences
12.11.2018 | Physics and Astronomy