[Abstract Title]. - Society for Neuroscience

Title: Cortical brain derived neurotrophic factor modulates expression of appetitive and aversive
learning in mice
Authors: *D. C. CHOI 1 , K. M. MYERS 1 , K. A. MAGUSCHAK 1 , K. J. RESSLER 2 ;
1 Dept Psychiatry, Emory Univ., Atlanta, GA; 2 Psychiatry, Emory University, Howard Hughes
Med. Inst., Atlanta, GA
Abstract: Considerable evidence suggests the medial prefrontal cortex (mPFC) is a major
modulator of fear conditioning and extinction by directly influencing the amygdala, but the
neural mechanisms are still unclear. One potential candidate may be brain derived neurotrophic
factor (BDNF), a neurotrophin that is well known to be involved in neuronal plasticity and has
been shown to be involved in learning, including fear conditioning. BDNF is highly expressed in
the medial prefrontal cortex. Therefore, we hypothesize that BDNF in the mPFC is a prime
candidate for mediating the learning and/or extinction of fear. To investigate this, a novel cortexspecific
BDNF knockout mouse line was generated by crossing homozygous BDNF-floxed mice
(loxP sites both upstream and downstream of BDNF exon 5), with a transgenic line that has
neocortex-specific expression of Cre-recombinase, to selectively knockout BDNF in select areas
of the neocortex. In normal mice, BDNF mRNA is abundantly expressed in the prefrontal cortex,
including the prelimbic and infralimbic cortices. In contrast, the cortical BDNF knockout mice
have pronounced loss of BDNF expression in the prelimbic cortex, while BDNF expression is
completely spared in the more ventrally located infralimbic cortex. The cortical BDNF knockout
mice were found to be no different than controls for various behavioral tests, including open
field, elevated plus maze, and novel object recognition, suggesting these knockout mice have
normal motor functioning, and unconditioned fear. However, with cue-dependent fear
conditioning we found that although cortical BDNF knockout mice had normal acquisition of
fear, they displayed a profound deficit in the expression of this previously learned fear behavior
(freezing) when tested the next day. A second set of BDNF knockout mice were trained on
cocaine conditioned place preference. In contrast to the fear expression deficit, the BDNF
knockout mice appear to have enhanced learning of cocaine preference. We propose that the
knockout of BDNF mRNA in the prelimbic cortex is the primary candidate responsible for a
deficit in expression of aversive learning and enhancement of appetitive learning.
Disclosures: D.C. Choi , None; K.M. Myers, None; K.A. Maguschak, None; K.J. Ressler,
None.
Poster
292. Acetylcholine, Neurotrophins, and Cognition
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 292.13/SS26