Three medial-temporal-lobe (MTL) structures--perirhinal cortex (PR), amygdala (AM), and hippocampus (HC)--are known to be critical for emotional and cognitive aspects of animal and human learning and memory. All three are also severely compromised in Alzheimer's disease (AD). Here we combine methods of behavioral and computational neuroscience to elucidate the manner in which performance declines within rat MTL circuits as a function of aging. Special focus is on PR/AM function because of the recognized importance of these two structures in emotional and cognitive aspects of learning and memory; because almost nothing is known about the functional consequences of aging associated changes in the cellular neurobiology of these structures, which we study in a separate but parallel in vitro research project; and because PR is one of the earliest brain regions to develop neurofibrillary tangles, which are characteristic of Alzheimer's disease. The role of PR/AM circuitry in aging-related performance decline has never been addressed. Our battery of conditioning procedures is designed to increase the performance demand on PR/AM circuits. I expect to create a set of more sensitive and circuit-specific Pavlovian measures of aging-related performance decline. The test battery will be combined with neurobiological manipulations to get a better understanding of normal PR function and its changes during aging. This theory-driven research should impact in three directions. First, it will furnish critical experimental data regarding normal PR/AM function that will test and/or be incorporated into our computational model of the neurophysiology of PR/AM-dependent fear conditioning. This is the only such model and we plan to develop it further. Second, the tests can be used to """"""""time stamp"""""""" circuit-specific changes during aging. This information is needed to detect and understand the temporal and causal relationship between particular changes in cognition and specific modifications in the underlying neurobiology. Third, the overall results will furnish a better basis for evaluating therapeutic treatment effects. Based on the """"""""calcium dysregulation"""""""" hypothesis for cognitive aging, a treatment strategy we shall explore involves pharmacologically altering a calcium-dependent potassium current that is thought to be altered in opposite directions by conditioning and aging.
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| Kent, Brianne A; Brown, Thomas H (2012) Dual functions of perirhinal cortex in fear conditioning. Hippocampus 22:2068-79 |
| Parsana, Ashwini J; Li, Nanxin; Brown, Thomas H (2012) Positive and negative ultrasonic social signals elicit opposing firing patterns in rat amygdala. Behav Brain Res 226:77-86 |
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| Bang, Sun Jung; Brown, Thomas H (2009) Perirhinal cortex supports acquired fear of auditory objects. Neurobiol Learn Mem 92:53-62 |
| Bang, Sun Jung; Brown, Thomas H (2009) Muscarinic receptors in perirhinal cortex control trace conditioning. J Neurosci 29:4346-50 |
| Allen, Timothy A; Narayanan, Nandakumar S; Kholodar-Smith, Dianna B et al. (2008) Imaging the spread of reversible brain inactivations using fluorescent muscimol. J Neurosci Methods 171:30-8 |
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