[Abstract Title]. - Society for Neuroscience

282. Stress and the Brain: Cellular Actions of Stress
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 282.23/OO30
Topic: E.06.d. Cellular actions of stress
Support: NIH Grant MH17871
Title: BDNF deficiency and stress have overlapping effects on apical dendrites and excitatory
transmission in medial prefrontal layer V pyramidal cells
Authors: *R.-J. LIU, G. K. AGHAJANIAN;
Dept Psychiatry, Yale Sch. Med., New Haven, CT
Abstract: Recently, we reported that stress-induced apical dendritic atrophy is associated with
diminished excitatory responses to apically-targeted excitatory inputs regulated by serotonin (5-
HT) and hypocretin in medial prefrontal cortex (mPFC) 1 . However, it remains unclear what
neurotrophic mechanisms may underlie these stress-induced changes. There is a growing body of
evidence that stress leads to decreased expression of brain-derived neurotrophic factor (BDNF)
in mPFC and other limbic structures, which could be related to changes in cortical dendrites 2 .
Previously, in BDNF conditional knockout mice, we have found a marked decrease in 5-HT2Amediated
excitatory postsynaptic currents (EPSCs) in layer V mPFC pyramidal cells 3 . Therefore,
we hypothesized that deficits in BDNF could contribute to the stress-induced changes in
morphology and function in layer V pyramidal cells. Using whole cell recording and two photon
laser scanning in brain slice, we examined both electrophysiological and morphological changes
in the same layer V pyramidal cells in wild type and heterologous BDNF knock out mice
(BDNF +/- ) after exposure to repeated mild immobilization stress. As in our previous rat studies,
we found that repeated stress in wild type mice results in a reduction in the frequency of 5-HT-
and hypocretin-induced EPSCs as well as a reduction in apical but not basal dendritic branch
length. In BDNF +/- mice, such deficits in dendritic branch length and EPSC responses were
already present, even in the absence of externally applied stress. Surprisingly, in BDNF +/- mice
there was no additional reduction in dendritic branch length and 5-HT-induced EPSCs after
repeated stress. In contrast, there was a further decrement in the frequency of hypocretin-induced
EPSCs after stress in the BDNF +/- mice. These results indicate that BDNF deficient mice have a
constitutive deficit in both apical dendritic branch length and 5-HT and hypocretin-induced
excitatory responses in layer V pyramidal cells. However, only hypocretin-modulated excitatory
EPSCs showed a further decrease in BDNF +/- mice after repeated stress, implying the
involvement of factors in addition to BDNF.
1. Liu and Aghajanian, Proc Natl Acad Sci U S A. (2008)105:359-64.
2. Gorski et al., J Neurosci. (2003) 23:6856-65.
3. Rios et al., J Neurobiol. (2006) 66:408-20.
Disclosures: R. Liu, None; G.K. Aghajanian, None.