Aging Changes The Neural Circuit Underlying Extinction of Fearful Memories
Mentor 1
James Moyer Jr.
Location
Union Wisconsin Room
Start Date
24-4-2015 2:30 PM
End Date
24-4-2015 3:45 PM
Description
Over 16 million people in the United States are living with some form of aging-related cognitive impairment. Understanding changes in brain function during aging is important in finding novel ways to combat aging-related cognitive decline, including impairments in cognitive flexibility. We use extinction of fear conditioning as an example of cognitive flexibility; during extinction animals learn that a neutral tone that was previously paired with a shock is no longer predictive of a shock. We have demonstrated that fear extinction is impaired in aging rodents (Kaczorowski et al, 2012). Since fear extinction is dependent on the activity of neurons in specific regions of the medial prefrontal cortex (mPFC), we hypothesize that aging-related changes in neuronal activity in these regions may be linked to impaired fear extinction. In the present study we measured neuronal activation by investigating changes in the expression of Zif-268 and c-fos proteins, markers used to label recently active neurons. Young, middle-aged, and aged rats were separated into four experimental groups; naïve, unpaired, trace fear conditioned (TRACE), and trace fear extinction groups (EXT). On day 1, TRACE and EXT rats were exposed to 10 tone-shock pairings where the tone was followed by the shock 30s later. Unpaired rats were presented 10 tones and shocks but these were not explicitly paired. On days 2 and 3, EXT and unpaired rats were given 10 tone presentations to extinguish the tone-shock association. On the 4th day, TRACE, EXT, and unpaired rats were given 2 tone presentations to obtain an index of fear learning and fear extinction. Brains were subsequently removed and prepared for immunohistochemical staining for Zif-268 and c-fos expression. Our data suggest that within the prelimbic and infralimbic subregions of the mPFC, Zif-268 and c-fos expression was increased in unpaired, TRACE and EXT groups. This effect was more robust in young compared to aging rats. Moreover, despite differences in Zif-268 and c-fos expression, middle-aged, and aged rats were able to acquire trace fear conditioning, as well as extinction. Therefore, fear learning may engage mPFC differentially in young and aged rats. These data suggest that there may be significant changes in the brain regions normally engaged during successful acquisition and extinction of trace fear conditioning, which may be important in development of neurotherapeutic strategies for improving cognitive function in aged animals, including humans.
Aging Changes The Neural Circuit Underlying Extinction of Fearful Memories
Union Wisconsin Room
Over 16 million people in the United States are living with some form of aging-related cognitive impairment. Understanding changes in brain function during aging is important in finding novel ways to combat aging-related cognitive decline, including impairments in cognitive flexibility. We use extinction of fear conditioning as an example of cognitive flexibility; during extinction animals learn that a neutral tone that was previously paired with a shock is no longer predictive of a shock. We have demonstrated that fear extinction is impaired in aging rodents (Kaczorowski et al, 2012). Since fear extinction is dependent on the activity of neurons in specific regions of the medial prefrontal cortex (mPFC), we hypothesize that aging-related changes in neuronal activity in these regions may be linked to impaired fear extinction. In the present study we measured neuronal activation by investigating changes in the expression of Zif-268 and c-fos proteins, markers used to label recently active neurons. Young, middle-aged, and aged rats were separated into four experimental groups; naïve, unpaired, trace fear conditioned (TRACE), and trace fear extinction groups (EXT). On day 1, TRACE and EXT rats were exposed to 10 tone-shock pairings where the tone was followed by the shock 30s later. Unpaired rats were presented 10 tones and shocks but these were not explicitly paired. On days 2 and 3, EXT and unpaired rats were given 10 tone presentations to extinguish the tone-shock association. On the 4th day, TRACE, EXT, and unpaired rats were given 2 tone presentations to obtain an index of fear learning and fear extinction. Brains were subsequently removed and prepared for immunohistochemical staining for Zif-268 and c-fos expression. Our data suggest that within the prelimbic and infralimbic subregions of the mPFC, Zif-268 and c-fos expression was increased in unpaired, TRACE and EXT groups. This effect was more robust in young compared to aging rats. Moreover, despite differences in Zif-268 and c-fos expression, middle-aged, and aged rats were able to acquire trace fear conditioning, as well as extinction. Therefore, fear learning may engage mPFC differentially in young and aged rats. These data suggest that there may be significant changes in the brain regions normally engaged during successful acquisition and extinction of trace fear conditioning, which may be important in development of neurotherapeutic strategies for improving cognitive function in aged animals, including humans.
