RT Journal Article
SR Electronic
T1 Haploinsufficiency in Peptidylglycine α-Amidating Monooxygenase Leads to Altered Synaptic Transmission in the Amygdala and Impaired Emotional Responses
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 13656
OP 13669
DO 10.1523/JNEUROSCI.2200-10.2010
VO 30
IS 41
A1 Eric D. Gaier
A1 Ramona M. Rodriguiz
A1 Xin-Ming M. Ma
A1 Shobhana Sivaramakrishnan
A1 Danielle Bousquet-Moore
A1 William C. Wetsel
A1 Betty A. Eipper
A1 Richard E. Mains
YR 2010
UL http://www.jneurosci.org/content/30/41/13656.abstract
AB The mammalian amygdala expresses various neuropeptides whose signaling has been implicated in emotionality. Many neuropeptides require amidation for full activation by peptidylglycine α-amidating monooxygenase (PAM), a transmembrane vesicular cuproenzyme and regulator of the secretory pathway. Mice heterozygous for the Pam gene (PAM+/−) exhibit physiological and behavioral abnormalities related to specific peptidergic pathways. In the present study, we evaluated emotionality and examined molecular and cellular responses that characterize neurophysiological differences in the PAM+/− amygdala. PAM+/− mice presented with anxiety-like behaviors in the zero maze that were alleviated by diazepam. PAM+/− animals were deficient in short- and long-term contextual and cued fear conditioning and required higher shock intensities to establish fear-potentiated startle than their wild-type littermates. Immunohistochemical analysis of the amygdala revealed PAM expression in pyramidal neurons and local interneurons that synthesize GABA. We performed whole-cell recordings of pyramidal neurons in the PAM+/− amygdala to elucidate neurophysiological correlates of the fear behavioral phenotypes. Consistent with these observations, thalamic afferent synapses in the PAM+/− lateral nucleus were deficient in long-term potentiation. This deficit was apparent in the absence and presence of the GABAA receptor antagonist picrotoxin and was abolished when both GABAA and GABAB receptors were blocked. Both evoked and spontaneous excitatory signals were enhanced in the PAM+/− lateral nucleus. Phasic GABAergic signaling was also augmented in the PAM+/− amygdala, and this difference comprised activity-independent and -dependent components. These physiological findings represent perturbations in the PAM+/− amygdala that may underlie the aberrant emotional responses in the intact animal.