Neuroscientists Reveal Precise Connections Between Retinal Nerve Cells and Midbrain Structure

For the first time, neuroscientists from Charité – Universitätsmedizin Berlin and the Max Planck Institute for Biological Intelligence (currently being established) have revealed the precise connections between sensory neurons inside the retina and the superior colliculus, a structure of the midbrain. Neuropixel probes are a relatively recent development, representing the next generation of electrodes. Densely packed with recording dots, Neuropixels probes are used to record nerve cell activity and have facilitated this recent insight into neural circuitry. write in Nature Communicationthe researchers describe a fundamental principle common to the visual systems of mammals and birds.

Two brain structures are crucial for processing visual stimuli: the visual cortex in the primary cerebral cortex and the superior colliculus, a structure in the midbrain. Seeing and processing visual information involve very complex processes. In simplified terms, the visual cortex is responsible for general visual perception, while structures in the older evolutionary midbrain are responsible for visually guided reflective behaviors. The mechanisms and principles involved in visual processing within the visual cortex are well known. Work by a team of researchers led by Dr. Jens Kremkow contributed to our knowledge in this area and in 2017 resulted in the establishment of an Emmy Noether Junior Research Group at the Charité Neuroscience Research Center (NWFZ). The main aim of the research group, which is funded by the German Research Foundation (DFG), is to further improve our understanding of the nerve cells involved in the visual system. Many questions remain unanswered, including details about how visual information is processed in the superior colliculi of the midbrain.

The retinal ganglion cells, sensory cells located inside the retina of the eye, respond to external visual stimuli and send the information received to the brain. Direct signaling pathways ensure that visual information received by retinal nerve cells also reaches the midbrain.

What had remained largely unknown until now was how retinal nerve cells and midbrain nerve cells are functionally related. The lack of knowledge regarding how neurons in the superior colliculi process synaptic inputs was also pronounced. This information is crucial to understanding the mechanisms involved in the processing of the midbrain.”

Dr Jens Kremkow, study leader

Until now, it was impossible to measure the activity of synaptically connected retinal and midbrain neurons in living organisms. For their most recent research, the research team developed a method based on measurements obtained with innovative high-density electrodes called Neuropixel probes. Specifically, Neuropixel probes are tiny arrays of linear electrodes with about a thousand recording sites along a narrow rod. Comprising 384 electrodes for simultaneous recording of the electrical activity of neurons in the brain, these devices were a game-changer in the field of neuroscience.

Researchers working at Charité and the Max Planck Institute for Biological Intelligence have now used this new technology to determine relevant midbrain structures in mice (superior colliculi) and birds (optic tectum). Both brain structures have a common evolutionary origin and play an important role in the visual processing of retinal input signals in both groups of animals. Their work led the researchers to a startling discovery: “Usually, this type of electrophysiological recording measures electrical signals from action potentials that originate in the soma, the cell body of the neuron,” says Dr. Kremkow. “In our recordings, however, we noticed signals that differed in appearance from normal action potentials. We then investigated the cause of this phenomenon and found that the midbrain input signals were caused by action potentials propagated in the ‘axonal trees’ (branches) of retinal ganglion cells Our findings suggest that novel electron array technology can be used to record electrical signals emanating from axons, projections from nerve cells that transmit neural signals. This is a brand new discovery.” In a world first, Dr. Kremkow’s team was able to simultaneously capture the activity of nerve cells in the retina and their connected synaptic target neurons in the midbrain.

Until now, the functional wiring between the eye and the midbrain had remained an unknown quantity. Researchers were able to show at the single-cell level that the spatial organization of retinal ganglion cell entries into the midbrain is a highly accurate representation of the original retinal entry. “The structures of the midbrain effectively provide an almost one-to-one copy of the retinal structure,” says Dr. Kremkow. He continues, “Another new finding for us is that neurons in the midbrain receive very strong and specific synaptic input from retinal ganglion cells, but only from a small number of these sensory neurons. These neural pathways allow a very structured and functional connection. between the retina of the eye and the corresponding regions of the midbrain.” Among other things, this new idea will improve our understanding of the phenomenon known as blind vision, which can be observed in people who have suffered damage to the visual cortex due to trauma or tumor.Incapable of conscious perception, these individuals retain a residual ability to process visual information, resulting in intuitive perception of stimuli, contours, movement, and even color which seems to be related to the midbrain.

To test whether the principles initially observed in the mouse model could also apply to other vertebrates – and therefore whether they could be more general in nature – Dr Kremkow and his team worked alongside a team of the Max Planck Institute for Biological Intelligence, where a Lise Meitner research group led by Dr. Daniele Vallentin focuses on the neural circuits responsible for coordinating precise movements in birds. “Using the same types of measurements, we were able to show that, in zebra finches, the spatial organization of the nerve pathways connecting the retina and midbrain follows a similar principle,” explains Dr Vallentin. She adds: “This finding was surprising, given that birds have significantly higher visual acuity and the evolutionary distance between birds and mammals is considerable.” The researchers’ observations suggest that the retinal ganglion cells of the optic tectum and superior colliculi show similar spatial organization and functional wiring. Their findings led the researchers to conclude that the discovered principles must be crucial for visual processing in the mammalian midbrain. These principles may even be general in nature, applying to all vertebrate brains, including those of humans.

Regarding the researchers’ future plans, Dr Kremkow says: “Now that we understand the functional mosaic connections between retinal ganglion cells and neurons in the superior colliculi, we will further explore how sensory signals are processed in the vision system, particularly in midbrain regions, and how they contribute to visually-guided reflective behavior.The team also wants to determine whether the new method could be used in other structures and whether it could be used to measuring axonal activity elsewhere in the brain If possible, it would open up a wealth of new opportunities to explore the underlying mechanisms of the brain.


Charity – Universitätsmedizin Berlin

Journal reference:

Sibille, J. et al. (2022) High-density electrode recordings reveal strong and specific connections between retinal ganglion cells and midbrain neurons. Communication Nature.