The goal of our research is to identify the neural mechanisms by which sleep enables memory consolidation. Sleep regulates many physiological processes and impairment of sleep is seen in many diseases that impair memory: Alzheimer's disease, Parkinson's disease, depression and sleep apnea. Many studies have demonstrated sleep deprivation following learning will impair memory. We will use behavioral experiments, electrophysiology and molecular biology to deduce the neural mechanisms responsible for sleep alterations after fear conditioning. We will use fear conditioning as a learning paradigm to because it is a single-trial task with a defined time course of memory consolidation. After fear conditioning, we have discovered that mice have a period of increased arousal followed by increased sleep three hours following fear conditioning. We have also seen changes in thalamo-cortical (delta) and hippocampal (theta) oscillations associated with sleep. During the period of arousal there is a decrease is both delta and theta oscillations, but during the following 2 hour sleep period there is an increase in delta and theta oscillations. We believe these change in sleep activity are essential to memory consolidation because when we sleep deprive mice following fear conditioning long-term memory consolidation is impaired.
In Specific Aim 1 we will identify changes in sleep after fear conditioning.
In Specific Aim 2 we will identify alterations in gene transcription and protein synthesis during sleep after fear conditioning.
In Specific Aim 3 we will examine the role of the cAMP/PKA/CREB signaling during sleep following fear conditioning in transgenic mice.
| Hellman, Kevin; Hernandez, Pepe; Park, Alice et al. (2010) Genetic evidence for a role for protein kinase A in the maintenance of sleep and thalamocortical oscillations. Sleep 33:19-28 |
| Hellman, Kevin; Abel, Ted (2007) Fear conditioning increases NREM sleep. Behav Neurosci 121:310-23 |
| Graves, Laurel A; Hellman, Kevin; Veasey, Sigrid et al. (2003) Genetic evidence for a role of CREB in sustained cortical arousal. J Neurophysiol 90:1152-9 |
