Specialized sites within nerve cells are responsible for a rapid balancing of the amount of activity in the brain.
To process information in our brains, nerve cells produce brief electrical impulses, called action potentials, triggered from one highly specialized region. Research from the Netherlands Institute for Neuroscience, together with researchers from Heidelberg University and the University of Göttingen in Germany, now show that the electrical trigger sites surprisingly change with experience; they are either becoming smaller with increasing number of experiences and, vice versa, they grow larger when less input arrives in the brain. The results were published in Nature Communications.
Exploring the environment
Rodents learn about their environment by moving their highly sensitive whiskers, with which they touch objects and, for example, identify food sources. To examine whether brain cells change with the number of sensory experiences, researchers from the Kole group, placed mice in an environment in which many new objects were present, with variable textures, shapes, and possibilities to explore. As a result of such a rich environment, brain cells shrank the length of the trigger site. With the shortening, which occurred even within a few hours, nerve cells also showed a lower rate by which electrical impulses were generated. In contrast, when sensory stimuli were not able to reach the brain because the whiskers were impaired, the trigger sites grew longer and produced more electrical impulses.
Structural changes of neurons are a phenomenon that scientists call ‘plasticity’ and form the basis of why we keep learning during our entire life and can adapt to an ever-changing world. Previously, it was thought that anatomical changes in nerve cells are primarily occurring at the contact sites called ‘synapses’. However, the present study shows that plasticity also occurs at the trigger sites for electrical impulses, which may be important to balance the amount of brain cell activity and prevent overexcitation. The question also remains which molecules are producing this type of plasticity.
The axon initial segment (AIS) is a critical microdomain for action potential initiation and implicated in the regulation of neuronal excitability during activity-dependent plasticity. While structural AIS plasticity has been suggested to fine-tune neuronal activity when network states change, whether it acts in vivo as a homeostatic regulatory mechanism in behaviorally relevant contexts remains poorly understood. Using the mouse whisker-to-barrel pathway as a model system in combination with immunofluorescence, confocal analysis and electrophysiological recordings, we observed bidirectional AIS plasticity in cortical pyramidal neurons. Furthermore, we find that structural and functional AIS remodeling occurs in distinct temporal domains: Long-term sensory deprivation elicits an AIS length increase, accompanied with an increase in neuronal excitability, while sensory enrichment results in a rapid AIS shortening, accompanied by a decrease in action potential generation. Our findings highlight a central role of the AIS in the homeostatic regulation of neuronal input-output relations.