Deciphering the functional organization of neuronal circuits controlling locomotion

Speaker: Ole Kiehn
Department: Neuroscience department
Subject: Deciphering the functional organization of neuronal circuits controlling locomotion
Location: Erasmus MC
Date: 06-03-2017
Author: Renée van der Winden

Ole Kiehn came to talk to us about his research on how locomotion is controlled by the nervous system. All the research he did was on mice, so everything that I will explain below has been seen in mice and not necessarily in humans. Dr. Kiehn distinguished two key features in locomotion, namely pattern generation and rhythm generation. The pattern generation is controlled by a dual system consisting of V0 neurons and non-V0 neurons in the spinal cord. The V0 neurons are split up into inhibitory and excitatory neurons. Which type they are is determined by the different transcription factors that are expressed along the spinal cord. By working together these neurons determine whether or not the mice move their left and right limbs synchronously or alternatingly. It turned out this decision is also influenced by the speed with which the mice move.

Seminar 4Figure 1: Schematic overview of pattern generation in mice

The rhythm generation happens in the brainstem instead of the spinal cord. Now the V2a neurons play an important role. They are excitatory and turned out to be essential for left/right alternation of the limbs. Another important factor here is the transcription factor Shox2. This is expressed in the ventral part of the spinal cord and works together with the transcription factor Chx10. It turned out that when the expression of Shox2 was affected, this reduced the frequency of the limb movement in locomotion. Clearly, Shox2 is involved with rhythm. It is thought it is driven by V2a neurons.

Dr. Kiehn also discussed how stopping and starting is regulated. This, too, happens in the brainstem. The mechanism used results in an active stop (as opposed to simply ‘not starting’ anymore). Again the V2a neurons play a role. They express Chx10 and act on an inhibitory network in the spinal cord to result in a controlled stopping of the locomotion. For starting movement the mesencephalic locomotor region (MLR) is the key player. This consists of two parts: the CNF and PPN. By stimulating the different regions it was found out that CNF invokes motion of all speeds and PPN only invokes motion of low speeds. Therefore it is thought that CNF is involved with escaping and PPN with explorative movement.

I thought this seminar was very interesting. I am interested in how the brain works and how it leads to people performing certain actions and having certain thoughts. I would like to explore the possibility of eventually doing research in the neuroscience field. I also thought the seminar was relatively easy to understand, which made it more enjoyable to listen to.

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