Maintaining and promoting healthy cognitive functions, of which memory is a most important one, is one of the major goals of mental health research. Diseases, stress, injury and aging can lead to cognitive and memory impairments. It is estimated that up to one third of adults will experience a gradual decline in cognitive function known as mild cognitive impairment as they age. Furthermore, a number of diseases such as Alzheimer's disease, autism, mental retardation are associated with memory impairments. Thus, minimizing or preventing cognitive and memory impairments is a very important goal in mental health. A principal approach toward this goal is to understand the physiological mechanisms of memory formation, persistence and storage and identify molecular mechanisms and targets that can be used to enhance memory, not only for potentiating normal functions but also for developing strategies that may prevent or reverse memory loss. Newly learned information that will become a long-term memory remains in a labile state for some time and becomes a long- term memory through a process of stabilization, known as memory consolidation. Using contextual fear conditioning types of memories in rats, we have recently found that hippocampal administration of the growth factor insulin like growth factor 2 (IGF-2) leads to potent memory enhancement and also increases memory persistence. Using inhibitory avoidance (IA) and other tasks like fear extinction and social transmission of food preference in rats and mice, this proposal aims at identifying the molecular mechanisms and brain circuitry of the IGF-2-mediated memory consolidation and enhancement. It will also test whether other members of the IGF system (IGF-1 and insulin) have memory-enhancing effects. Finally, with preclinical and translational goals in mind, given that IGF-2 readily passes the blood brain barrier, it will determine whether systemic treatments with IGF-2 are effective in enhancing memories retention and persistence and whether the IGF-2-dependent effect alters memory flexibility. Results from these studies should advance our knowledge of neural mechanisms that may be employed to achieve memory enhancement and to treat cognitive impairments.
Capitalizing on recent findings from our ongoing project using rats and mice as animal models, this project continuation aims at identifying the mechanisms by which insulin like growth factor 2 (IGF-2), IGF-1 and insulin promote memory consolidation, enhancement and persistence in adult animals. The results of these studies should lead to the understanding of mechanisms of memory consolidation and enhancement and the discovery of novel tools and targets important for strengthening normal memories and reducing the progression of memory decay and/or reversing memory loss in diseases. Preventing or rescuing cognitive and memory loss, is a most important goal in mental health research.
|Travaglia, Alessio; Steinmetz, Adam B; Miranda, Janelle M et al. (2018) Mechanisms of critical period in the hippocampus underlie object location learning and memory in infant rats. Learn Mem 25:176-182|
|Katzman, Aaron; Alberini, Cristina M (2018) NLGN1 and NLGN2 in the prefrontal cortex: their role in memory consolidation and strengthening. Curr Opin Neurobiol 48:122-130|
|Alberini, Cristina M; Cruz, Emmanuel; Descalzi, Giannina et al. (2018) Astrocyte glycogen and lactate: New insights into learning and memory mechanisms. Glia 66:1244-1262|
|Jia, Margaret; Travaglia, Alessio; Pollonini, Gabriella et al. (2018) Developmental changes in plasticity, synaptic, glia, and connectivity protein levels in rat medial prefrontal cortex. Learn Mem 25:533-543|
|Steinmetz, Adam B; Stern, Sarah A; Kohtz, Amy S et al. (2018) Insulin-Like Growth Factor II Targets the mTOR Pathway to Reverse Autism-Like Phenotypes in Mice. J Neurosci 38:1015-1029|
|Alberini, Cristina M; Travaglia, Alessio (2017) Infantile Amnesia: A Critical Period of Learning to Learn and Remember. J Neurosci 37:5783-5795|
|Travaglia, Alessio; Bisaz, Reto; Sweet, Eric S et al. (2017) Erratum: Infantile amnesia reflects a developmental critical period for hippocampal learning. Nat Neurosci 20:1033|
|Zhang, Yili; Smolen, Paul; Alberini, Cristina M et al. (2016) Computational model of a positive BDNF feedback loop in hippocampal neurons following inhibitory avoidance training. Learn Mem 23:714-722|
|Knight, Elysse M; Kim, Soong Ho; Kottwitz, Jessica C et al. (2016) Effective anti-Alzheimer A? therapy involves depletion of specific A? oligomer subtypes. Neurol Neuroimmunol Neuroinflamm 3:e237|
|Finsterwald, Charles; Steinmetz, Adam B; Travaglia, Alessio et al. (2015) From Memory Impairment to Posttraumatic Stress Disorder-Like Phenotypes: The Critical Role of an Unpredictable Second Traumatic Experience. J Neurosci 35:15903-15|
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