Advanced microscopy reveals how hormonal fluctuations shape the brain

Hormone levels fluctuate like tides, decrease and flow according to carefully orchestrated cycles. These hormones not only influence the body, but can cross the brain and shape the behavior of our neurons and cognitive processes. Recently, UC Santa Barbara researchers used modern laser microscopy techniques to observe how fluctuations in ovarian hormones shape both the structure and the function of neurons in the mouse hippocampus, a crucial brain region for memory formation and spatial learning in mammals. They discovered that hormonal fluctuations during the Stan of Mouse cycle, a 4 -day cycle analogous to the 28 -day human menstrual cycle, powerfully influence the form and behavior of hippocampus neurons.

“We have known for some time that ovarian hormones, and particularly estradiol, a type of estrogen, have important consequences for the structure and function of neurons,” said UCSB neuroscientist Michael Gard, the lead author of an article published in the Neuron magazine. In the 1990s, ex -vivo experiments examined the brain tissue of female rodents taken at different stages of the Elential Cycle. They discovered that during the “Proestrus” stage, when estradiol levels reach their maximum point, neurons in the hippocampus tend to form more dendritic spines, small protuberances that extend from the dendrites of the neurons and serve as the primary site of the connections between the neurons.

To date, there was little understanding of how the opening cycle affects neurons in living mice. “

Nora Wolcott, main author of the newspaper

Now, thanks to the advanced microscopy techniques, the Goard team could measure the structure and activity of neurons in multiple narrow cycles, thus obtaining an idea of ​​the role of sex hormones in the plasticity and memory of the brain. Other authors in the newspaper include William Redman, Marie Karpinska and Emily Jacobs.

Hormone -driven plasticity

Located in the depths of the brain of mammals, the hippocampus is a brain region associated mainly with memory and learning. Patients with hippocampus injuries cannot learn new information or form new episodic memories. The hippocampus is also enriched with receptors for sex hormones, such as estrogen and progesterone, suggesting that sex hormones not only influence reproduction, but also in cognitive functions such as memory.

Increasing where the previous studies remained, the researchers deployed a two -photon laser scan microscopy, tracking the formation and pruning of these dendritic thorns into mice for several four -day estrus cycles. Many new thorns observed during the Proestro, which were then pruned as the cycle advanced through ovulation. These were not subtle changes: the density of the thorns differed by 20-30% throughout the cycle, which represents thousands of synaptic connections for each neuron.

“How do the flow and flow of thorns influence the function of brain cells? Perhaps this influences how neurons integrate the signs of other neurons,” Gard said. “You can imagine if you suddenly add more synaptic connections, neurons will get much more information and this will affect the way they respond.”

To investigate, the scientists examined the action potential, the “shot” of the neuron, and how the impulse is spread through the neuron. Typically, the dendrites receive the signal, which travels to the cell body and the axon. “But the signal also travels back through the dendrite, which is generally where the neuron receives information,” Goard said. It is believed that this recoil signal plays a role in learning and consolidation of memory. They discovered that during the estradiol peak, the backward signal resorted to the dendrites, that researchers suspect that they can have implications for plasticity: the brain capacity to form new neuronal connections.

So what are the functional consequences of increasing the density of the dendritic column and backing? An answer lies in the “place cells”, or neurons in the hippocampus that shoot when the animal is in a particular location in its environment: they help build mental maps and help with spatial learning and navigation. To prove the ability of animals to learn and remember new places, researchers allowed them to explore different environments while measuring the activity of neurons in the hippocampus.

The researchers found that the place cells responded to family locations more reliable during the Proestro, the high estradiol phase, and were more variable when the estradiol was lower. “This is the first time that these microscopic differences in neural structure and function have been tracked over time in the same animal,” Wolcott said.

These findings in mice also have strong implications for humans. In fact, the work of the Laboratory of Co -author Emily Jacobs found that endocrine rhythms in the menstrual cycle are linked to structural changes in the human hippocampus. While hormonal cycles are typically associated with female mammals, males also experience hormonal fluctuations, many of which act in similar receptors. For example, testosterone can become estrogen through aromatization, where it acts on estrogen receptors in the hippocampus. This indicates that hormones driven is a generalized phenomenon and underlines the importance of considering endocrine factors in neuroscience research.

“We suspect that there is some adaptive evolutionary purpose,” said Gard, “and the reason why I suspect that this is because receptors for ovarian hormones do not have to be in the hippocampus, which is not believed that it does not directly get involved in reproductive functions. But for some reason they are being expressed in the hippocampus, probably for some related purposes and memory. It is, but we believe it is important in the hippocampus. “

Understanding the relationship between the fluctuations of the hormonal cycle and the brain not only promotes our fundamental understanding of brain biology, but also opens new possibilities for personalized medicine not only for individuals, but with respect to the hormonal cycle phase. “The finding that the brain changes physically in response to cycling hormones naturally challenges our understanding of mammalian cognition,” Wolcott said.