Have you ever wondered about what it is that could be going awry at the microscopic level to cause some of the devastating symptoms that are evident in so many diseases? Whether you have or haven’t, this is a question a lot of biomedical scientists find themselves asking. For most diseases there exists a set of well-described symptoms that are used to identify, diagnose, and treat patients. However, for these same diseases, it can be an enormous challenge to be able to identify the exact cellular and molecular causes. In the most recent issue of The Journal of Neuroscience, a group of researchers out of Sweden have identified important cellular changes in a mouse model of Huntington’s disease (HD), changes that are made worse by modifying the sensory experience of these animals.
In this study, Murmu et al. probe the synaptic deficits associated with HD by using a fluorescent imaging technique, two-photon microscopy, in a mouse model of the disease. Two-photon microscopy allows researchers to image deeper into tissue and to image cellular features in alive animals. By using this technique the authors were able to track the changes in dendritic spines, small protrusions located on neuronal processes where excitatory synapses are made, in order to study how these structures change in relation to the sensory experience of these HD animals.
The authors of the study have previously shown deficits in the synaptic spines of these mice as baseline. Specifically, the authors have shown that the number of “persistent-type” spines, a set of spines important for maintaining neural circuitry and for normal learning and memory, are decreased in HD mice. In this study, to investigate how sensory experience further alters spines in these animals, the authors trimmed the whiskers of control and HD model mice, a treatment that would disrupt the normal sensory perception experienced by these mice. Sensory experience is known to modulate synaptic connections and specific forms of plasticity that are based on sensory experience. Thus, this manipulation allowed the authors to measure how this change in sensory experience might drive changes in dendritic spines. Interestingly, it was found that this treatment actually exacerbated the spine deficits that are normally seen at baseline in these mice. Specifically, the authors quantified what they define as “lost persistent” (LP) spines, spines that were persistent early on but subsequently disappeared. In the HD animals, whisker trimming increased the spine density of LP spines, indicating that sensory experience has larger effects on synaptic spines in the HD animals than in the control animals.