Blue light triggers memory and emphatic fear in mice via a non-invasive approach

January 21, 2020

Science Daily/Institute for Basic Science

Researchers at the Center for Cognition and Sociality, within the Institute for Basic Science (IBS) in South Korea, have engineered an improved biological tool that controls calcium (Ca2+) levels in the brain via blue light. Published in Nature Communications, this optogenetic construct, called monster-OptoSTIM1 or monSTIM1 for short, causes a change in mice's fear learning behavior without the need of optic fiber implants in the brain.

The brain utilizes Ca2+ signaling to regulate a variety of functions, including memory, emotion, and movement. Several evidences show correlation between abnormally regulated Ca2+ levels in certain brain cells and neurodegenerative diseases, but the details still remain obscure. For understanding the precise role of Ca2+ signaling, the IBS team is studying Ca2+-specific modulators that can be triggered in different parts of the brain at a designated time.

Optogenetics uses light to control Ca2+ signaling in the mouse brain. Since the brain is surrounded by hair, skin and skull, which prevent light from reaching deep tissues, optic fiber insertion in the brain used to be the norm in optogenetics. However, these implants can cause inflammation, morphological changes of neurons and disconnection of neural circuits. In this study, the research team improved their optogenetic tool so that it works with an external source of blue light, shone from the ceiling of the mouse cage, and without the need of brain implants.

MonSTIM1 is made of a part (CRY2) that responds to blue light and another part (STIM1) that activates calcium channels. Compared to the previously developed optogenetic techniques, the researchers were able to enhance CRY2's light-sensitivity approximately 55-fold and also avoid the increase of basal Ca2+ levels. The monSTIM1 construct was injected into the mouse brain through a virus, and was shown to activate Ca2+ signals in the cortex as well as in the deeper hippocampus and thalamus regions.

The team observed behavioral changes in mice with monSTIM1 expressed in excitatory neurons in the anterior cingulate cortex, a brain region that has a central function in empathic emotions. Mice with activated monSTIM1 froze with fear by looking at other mice, which experienced a mild electric foot shock. Twenty-four hours later the same mice remembered about it and showed again an enhanced fear response, indicating that Ca2+ signaling contributed to both short- and long-term social fear responses.

"MonSTIM1 can be applied to a wide range of brain calcium research and brain cognitive science research, because it allows easy manipulation of intracellular calcium signals without damaging the brain," says Won Do Heo (KAIST professor), leading author of this research.

https://www.sciencedaily.com/releases/2020/01/200121123953.htm

Brain waves in mice change based on memory age

December 17, 2019

Science Daily/RIKEN

Researchers have discovered signatures in brain activity that allow them to tell old and new memories apart. The team analyzed recordings from mouse brains using a machine-leaning algorithm, which was able to accurately classify memories as recent or remote. They also found robust communication between a frontal brain region and the hippocampus, a link which may form a concrete mechanism that tracks the age of memories.

Identifying the location and persistence of memories in the brain has implications for cases of brain damage, memory loss, and clinical memory impairment. In this study, the researchers were interested in how different brain areas that contain memory traces interact, especially during memory recall. The anterior cingulate cortex (ACC) in the prefrontal brain is known to be anatomically connected to the hippocampus. The team wanted to study this connection more closely, at the level of signals from individual neurons.

They recorded activity in both brain areas before exposing mice to a memory-forming experience (a foot shock), and then again in the same cage both one day and one month later. If mice froze in the same context, it was a behavioral indication that they remembered the shock. But the neuronal recordings also revealed that the ACC and hippocampus, specifically area CA1, are highly synchronized when mice recall the fear memory.

The interactions of the two brain areas changed over time, with ACC and CA1 activity becoming more correlated when an old or 'remote' memory was recalled compared to the recent, one-day memory. Specific frequencies and modes of neural activity became more pronounced between the two areas when the mice recalled the older memory, with the ACC appearing to drive activity in hippocampus in a top-down manner. "While memory is consolidated over time in frontal areas, we think in this case the ACC is facilitating the retrieval of contextual details back from the hippocampus," said senior author and team leader Thomas McHugh of RIKEN CBS.

The evolving pattern of signals over time allowed the researchers to distinguish old and new memories in mice from the brain recordings alone. "We could decode whether a mouse was recalling a recent or remote memory by looking at the correlations in ACC-CA1 interactions," said McHugh. Moreover, the researchers suggest that a small group of CA1 neurons carries the information about memory age.

"While we have known for 20 years that the ACC is important for recalling older memories, how it contributes has remained a mystery" McHugh explained. "We found that it plays in important role in organizing activity in the hippocampus, the part of the brain in which the memory was originally formed. This suggests the hippocampus always plays a role in providing key details of an old experience, at least in the healthy brain."

The team is now focused on understanding how impairments in long-term memory that often accompany aging and disease impacts activity in these brain circuits.

https://www.sciencedaily.com/releases/2019/12/191217114229.htm