Fear ConditioningFear Conditioning

Maladaptive behaviors such as anxiety disorders are associated with learning and
memory processes. Fear conditioning is often used as a model for understanding anxiety
disorders including post-traumatic stress disorder (PTSD). Like CPP experiments, fear
conditioning is based on Pavlovian conditioning in which an organism learns to predict
aversive events based on associative learning. The expression of learned fear functions to
prepare an organism for “fight or flight” responding.
An investigation of how memory strength influences the recruitment of different
signaling molecules will be of immense clinical value that could be applicable to the
treatment of many debilitating learning and memory diseases. I had shown that altering
the stimulus salience of cocaine reward engages different neural substrates. However, it is
unclear whether this effect is specific to appetitive learning and memory or if this
phenomenon is applicable to other paradigms of learning and memory. My preliminary
work used the fear conditioning model to assess how changing the stimulus salience
affects the acquisition of fear memory. Mice were divided into two groups: a) Fixed
shock: mice given 4 shocks, each at 1.1mA intensity and b) Escalating shock: mice
given 4 shocks at increasing intensities (0.6, 0.8, 1.2 and 1.8mA). The intensity for the
fixed shock group represents the average shock intensity over 4 shocks of the escalating
shock group. Thus, I controlled for the total shock intensity to which mice were exposed.
Figure 5.2 shows the effect of the different training schedules on conditioned contextual
freezing response. Mice conditioned by escalating shock intensities show higher freezing
which was generally resistant to unreinforced exposures to the training context. However,
mice conditioned by fixed shock intensities showed a significantly lower magnitude of
freezing and freezing levels at the second test (re-test 1; day 6) and subsequent tests were
not statistically different from basal freezing levels. Results suggest that an escalating
regimen of conditioning, be it appetitive or aversive, results in ‘stronger’ memory. Future
studies should investigate whether these behavioral differences between conditioning by
fixed and escalating shock intensities engage different signaling pathways in the
formation of fear memory. Additionally, an investigation of the contribution of NR2Bcontaining
NMDARs in determining memory strength would solidify the involvement of
the NR2B subunit as an important regulator of memory strength. This would therefore
identify NR2B-containing NMDARs as potential targets for the treatment of myriad
maladaptive behaviors that arise from Pavlovian conditioning.

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