New findings of cortical activity during delta wave sleep sheds further light into memory formation

Scientists at the Center for Interdisciplinary Research in Biology have shown that delta waves emitted while we sleep are not generalized periods of silence during which the cortex rests, as has been described for decades in the scientific literature. Instead, they isolate assemblies of neurons that play an essential role in long-term memory formation. These results were published in journal Science.

While we sleep, the hippocampus reactivates itself spontaneously by generating activity similar to that while we are awake. It sends information to the cortex, which reacts in turn. This exchange is often followed by a period of silence called a ‘delta wave’ then by a rhythmic activity called a ‘sleep spindle’. This is when the cortical circuits reorganize to form stable memories.

However, the role of delta waves in the formation of new memories is still a puzzle: why does a period of silence interrupt the sequence of information exchanges between the hippocampus and the cortex, and the functional reorganization of the cortex?

The authors here looked more closely at what happens during delta waves themselves. They discovered, surprisingly, that the cortex is not entirely silent but that a few neurons remain active and form assemblies, i.e. small, coactive sets that code information. This unexpected observation suggests that the small number of neurons that activate when all the others stay quiet can carry out important calculations while protected from possible disturbances.

And the discoveries from this work go even further! Spontaneous reactivations of the hippocampus determine which cortical neurons remain active during the delta waves and reveal transmission of information between the two cerebral structures. In addition, the assemblies activated during the delta waves are formed of neurons that have participated in learning a spatial memory task during the day. Together these elements suggest that these processes are involved in memory consolidation.

To demonstrate it, in rats the scientists caused artificial delta waves to isolate either neurons associated with reactivations in the hippocampus or random neurons. Result: when the right neurons were isolated, the rats managed to stabilize their memories and succeed at the spatial test the next day.

Exercise improves memory in Diabetic rats

University of Tsukuba led researchers shows that moderate exercise may improve hippocampal memory dysfunction caused by type 2 diabetes and that enhanced transport of lactate to neurons may be the underlying mechanism.

Type 2 diabetes is characterized by impaired glucose metabolism and can cause central nervous system-related complications, such as memory dysfunction. The hippocampus is an essential brain component for normal memory formation. However, the effect of impaired glycometabolism on hippocampal-mediated memory in type 2 diabetes patients is not known.

In a new study, researchers centered at the University of Tsukuba investigated whether hippocampal glucose metabolism and memory function are altered in a rat model of type 2 diabetes. Based on the idea that exercise normalizes glycometabolism and improves memory function, the research team also investigated the effects of exercise on hippocampal glycometabolism and memory formation.

The hippocampal function was evaluated by placing the rat in a circular pool and testing its ability to remember the location of a platform that would allow it to escape from the water. “This is a well-established method for measuring spatial learning and memory,” study first author Takeru Shima says.

Type 2 diabetic rats needed more time to escape the water and find the platform. However, after 4 weeks of moderate exercise, they were able to find the platform much faster. “This indicated that exercise significantly improved spatial memory impairments in type 2 diabetic rats,” Shima explains.

Glycogen levels are altered in tissues of diabetes patients, leading to a variety of complications. However, glycogen levels have not yet been investigated in the hippocampus. “We showed for the first time that glycogen levels are significantly higher in the hippocampus of diabetic rats,” corresponding author Hideaki Soya says.

Interestingly, a single bout of exercise reduced hippocampal glycogen levels and this correlated with an increase in lactate levels. Lactate is an energy substrate and neuromodulator in the hippocampus and is known to enhance memory formation. Lactate is transferred to neurons through monocarboxylate transporters (MCTs). “MCT2 expression was significantly lower in the hippocampus of type 2 diabetic rats,” Soya says, “dysregulated MCT2-mediated neuronal uptake of lactate is a possible etiology of memory dysfunction in type 2 diabetes, and that elevated hippocampal glycogen may be an adaptive change to compensate for the decreased lactate utilization”.

4 weeks of moderate exercise further enhanced glycogen levels and normalized MCT2 expression in the hippocampus of type 2 diabetic rats.” These findings suggest that disrupted MCT2-mediated uptake of lactate by neurons contributes to memory dysfunction in type 2 diabetic rats.

The findings indicate that moderate exercise could be used to treat memory impairment in patients with type 2 diabetes by promoting the transfer of glycogen-derived lactate to hippocampal neurons. Further research is needed to see if this correlates in human beings.

Citation: Shima, Takeru, Takashi Matsui, Subrina Jesmin, Masahiro Okamoto, Mariko Soya, Koshiro Inoue, Yu-Fan Liu, Ignacio Torres-Aleman, Bruce S. McEwen & Hideaki Soya. “Moderate exercise ameliorates dysregulated hippocampal glycometabolism and memory function in a rat model of type 2 diabetes.” Diabetologia 2016 pp: 1-10.
DOI: 10.1007/s00125-016-4164-4
Research funding: Ministry of Education, Culture, Sports, Science and Technology – Japan, Japan Society for the Promotion of Science.
Adapted from press release by University of Tsukuba.

Role of Hippocampus in future thinking and scene construction

Over the past decade, researchers have learned that the hippocampus historically known for its role in forming memories is involved in much more than just remembering the past; it plays an important role in imagining events in the future. Yet, scientists still do not know precisely how the hippocampus contributes to episodic imagining until now. Researchers from Boston University School of Medicine (BUSM) have determined the role of the hippocampus in future imaging lies in the process of constructing a scene in one’s mind.

Hippocampus. Credit: Wikipedia.

The findings, which appear in the journal Cerebral Cortex, shed important light on how the brain supports the capacity to imagine the future and pinpoints the brain regions that provide the critical ingredients for performing this feat.

The hippocampus is affected by many neurological conditions and diseases and it also can be compromised during normal aging. Future thinking is a cognitive ability that is relevant to all humans. It is needed to plan for what lies ahead, whether to navigate daily life or to make decisions for major milestones further in the future.

Using functional Magnetic Resonance Imaging, BUSM researchers performed brain scans on healthy adults while they were imagining events. They then compared brain activity in the hippocampus when participants answered questions pertaining to the present or the future. After that, they compared brain activity when participants answered questions about the future that did or did not require imagining a scene. “We observed no differences in hippocampal activity when we compared present versus future imaging, but we did observe stronger activity in the hippocampus when participants imagined a scene compared to when they did not, suggesting a role for the hippocampus in scene construction but not mental time travel,” explained corresponding author Daniela Palombo, PhD, postdoctoral fellow in the memory Disorders Research Center at BUSM and at the VA Boston Healthcare System.

According to the researchers, the importance of studying how the hippocampus contributes to cognitive abilities is bolstered by the ubiquity of hippocampal involvement in many conditions. “These findings help provide better understanding of the role of the hippocampus in future thinking in the normal brain, and may eventually help us better understand the nature of cognitive loss in individuals with compromised hippocampal function,” she added.

Palombo believes that once knowledge about which aspects of future imagining are and are not dependent on the hippocampus, targeted rehabilitation strategies can be designed that exploit those functions that survive hippocampal dysfunction and may provide alternate routes to engage in future thinking.

Citation: Palombo, D. J., S. M. Hayes, K. M. Peterson, M. M. Keane, and M. Verfaellie. “Medial Temporal Lobe Contributions to Episodic Future Thinking: Scene Construction or Future Projection?.” Cerebral Cortex (2016).
DOI: 10.1093/cercor/bhw381
Adapted from press release by Boston University School of Medicine.