Maintaining and promoting healthy cognitive functions, of which memory is a most important one, is one of the major goals of mental health research. Identifying mechanisms of long-term memory formation and targets that help in preventing or treating memory impairments is an important goal in mental health. Thus far, the studies of mechanisms underlying cognitive functions including memory have mainly focused on elucidating the contribution of neurons and neuronal networks. However, findings of the last few decades indicate that astrocytes actively participate in the regulation of synaptic functions including long-term plasticity and memory. Very little is known about the nature and functions of these astrocytic mechanisms. Furthermore, very little is known also about possible involvement of astrocytic functions in memory and cognitive impairments. Using a contextual fear conditioning memory task in rats we have recently identified a critical role of astrocytes- dependent metabolic coupling with neurons in long-term memory formation in rats. These findings show, for the first time to our knowledge, that, in a mammalian brain, astrocytes play a necessary and active role in long-term memory formation. This proposal aims at further investigating the biological mechanisms of astrocytes and their interactions with neurons in long-term memory formation and in memory impairments that accompany stress-related cognitive impairments. Importantly, mechanisms underlying memory formation during early development and in adulthood will be investigated to determine similarities and differences. Results from these studies should advance our knowledge of the biological mechanisms underlying memory formation and should lead to novel hypotheses and tools for understanding cognitive functions and preventing or reversing cognitive impairments linked to stress-related cognitive disorders.
Capitalizing on recent findings from our laboratory using rats as animal models, this project aims at identifying mechanisms by which astrocytes critically contribute to long-term memory formation in both young and adult animals under normal conditions and conditions of stress that leads to cognitive impairments. The results of these studies should provide novel understanding about how astrocyte-neuron interactions support normal cognitive function, and how regulation and dysregulation of astrocyte-neuron metabolic coupling may contribute to mental diseases. Hence, these results may provide insight for developing new strategies to treat memory and cognitive/mood disorders.