Nerve cell receptors help form memories

With each new piece of information or sensory experiences, our dynamic and malleable brain alters its connections which leads to long-lasting changes in neural pathways. While the misconception of the inert brain has mostly subsided, the underlying molecular mechanisms resulting in structural changes in neurons are still under much scrutiny in neuroscience.

Recently, Hopkins researchers succeeded in visualizing and tracking receptor proteins associated with memory formation in the brains of test animals.

Conducted by Yong Zhang, a postdoctoral fellow in neuroscience, and other members of the Huganir Lab, the study delineates the effects of sensory stimulation on cell receptors called α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) in living mice.

AMPAR receptors, located on the outside of nerve cells, have been of special interest for neuroscientists due to the receptors’ critical role in transmitting neural signals between cells.

In previous studies, researchers were limited to observing AMPAR activity in isolated tissue samples or nerve cells that were grown in the laboratory. This study, however, has shown that it is possible to observe AMPAR activity amidst the complex circuitry of a living nervous system by applying imaging techniques.

One of the techniques the researchers used was two-photon microscopy, which can take images of living tissue up to a certain depth. Under the light of this specialized microscope, the researchers are able to delve about 0.5 millimeters into the brains of living mice.

The scientists used two-photon microscopy to examine the AMPAR activity in the primary somatosensory cortex. The primary somatosensory cortex is the main sensory area for touch, and in the case of mouse brains, the primary somatosensory cortex is mapped such that it is divided by discrete anatomical units called barrels, each corresponding to an individual whisker.

To study whether sensory excitation of the whiskers could result in a difference in AMPAR dynamics, the researchers stimulated a single mouse whisker for one hour, taking images before and after the stimulation of the barrel that corresponds to the affected whisker.

The research team observed that following whisker stimulation there was a 30 percent average increase in AMPAR intensity in dendritic spines, which are door-knob shaped structures protruding from the surfaces of dendrites, located in the affected barrel. The increase of AMPAR intensity in the dendritic spines occurred rapidly within the first hour of the whisker stimulation and lasted for at least three hours.

Moreover, the sensory manipulation of the single whisker did not cause a significant change of AMPAR intensity in the barrels that corresponded to other whiskers.

This discovery of the increased AMPAR intensity in dendritic spines led to further investigations into the effects of whisker stimulation on dendritic spine turnover, the loss of old spines and the growth of new ones, which has been implicated in memory formation and learning. The researchers, however, did not find a substantial correlation between the whisker stimulation and the rate of dendritic spine turnover.

Nevertheless, this study’s findings concerning the increase in AMPAR intensity in dendritic spines imply that the whisker-tickling sensory stimulation may have instigated the formation of long-term memories in mouse brains. Moreover, the techniques utilized in this study would provide the tools by which scientists can hope to further address questions related to memory formation.

One application may be the visualization of AMPAR activity in the cognitively normal brains of mice as they learn a motor task. Another comparative study may be the observation of AMPAR activity in mouse models of brain disorders. These applications in future studies may lead to crucial insights not only into learning, but also into the problems in brains afflicted with neurological disorders such as autism, schizophrenia and Alzheimer’s disease.

The success of the visualization of AMPAR dynamics in vivo opens up many vistas of neuroscience research and increases the number of studies that can help further our understanding of how the brain operates.