In vivo and in vitro analyses of amygdalar function reveal a role for copper

E. D. Gaier, R. M. Rodriguiz, J. Zhou, Martina Ralle, W. C. Wetsel, B. A. Eipper, R. E. Mains

Research output: Contribution to journalArticle

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Abstract

Mice with a single copy of the peptide amidating monooxygenase (Pam) gene (PAM+/-) are impaired in contextual and cued fear conditioning. These abnormalities coincide with deficient long-term potentiation (LTP) at excitatory thalamic afferent synapses onto pyramidal neurons in the lateral amygdala. Slice recordings from PAM+/- mice identified an increase in GABAergic tone (Gaier ED, Rodriguiz RM, Ma XM, Sivaramakrishnan S, Bousquet-Moore D, Wetsel WC, Eipper BA, Mains RE. J Neurosci 30: 13656-13669, 2010). Biochemical data indicate a tissue-specific deficit in Cu content in the amygdala; amygdalar expression of Atox-1 and Atp7a, essential for transport of Cu into the secretory pathway, is reduced in PAM+/- mice. When PAM+/- mice were fed a diet supplemented with Cu, the impairments in fear conditioning were reversed, and LTP was normalized in amygdala slice recordings. A role for endogenous Cu in amygdalar LTP was established by the inhibitory effect of a brief incubation of wild-type slices with bathocuproine disulfonate, a highly selective, cell-impermeant Cu chelator. Interestingly, bathapplied CuSO4 had no effect on excitatory currents but reversibly potentiated the disynaptic inhibitory current. Bath-applied CuSO4 was sufficient to potentiate wild-type amygdala afferent synapses. The ability of dietary Cu to affect signaling in pathways that govern fear-based behaviors supports an essential physiological role for Cu in amygdalar function at both the synaptic and behavioral levels. This work is relevant to neurological and psychiatric disorders in which disturbed Cu homeostasis could contribute to altered synaptic transmission, including Wilson's, Menkes, Alzheimer's, and prion-related diseases.

Original languageEnglish (US)
Pages (from-to)1927-1939
Number of pages13
JournalJournal of Neurophysiology
Volume111
Issue number10
DOIs
StatePublished - 2014

Fingerprint

Amygdala
Long-Term Potentiation
Copper
Fear
Synapses
Prion Diseases
Aptitude
Pyramidal Cells
Secretory Pathway
Chelating Agents
Mixed Function Oxygenases
Nervous System Diseases
Baths
Synaptic Transmission
Psychiatry
Homeostasis
Diet
Peptides
In Vitro Techniques
Genes

Keywords

  • Fear
  • GABA
  • Learning and memory
  • Peptidylglycine alpha-amidating monooxygenase
  • Synaptic plasticity

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)
  • Medicine(all)

Cite this

Gaier, E. D., Rodriguiz, R. M., Zhou, J., Ralle, M., Wetsel, W. C., Eipper, B. A., & Mains, R. E. (2014). In vivo and in vitro analyses of amygdalar function reveal a role for copper. Journal of Neurophysiology, 111(10), 1927-1939. https://doi.org/10.1152/jn.00631.2013

In vivo and in vitro analyses of amygdalar function reveal a role for copper. / Gaier, E. D.; Rodriguiz, R. M.; Zhou, J.; Ralle, Martina; Wetsel, W. C.; Eipper, B. A.; Mains, R. E.

In: Journal of Neurophysiology, Vol. 111, No. 10, 2014, p. 1927-1939.

Research output: Contribution to journalArticle

Gaier, ED, Rodriguiz, RM, Zhou, J, Ralle, M, Wetsel, WC, Eipper, BA & Mains, RE 2014, 'In vivo and in vitro analyses of amygdalar function reveal a role for copper', Journal of Neurophysiology, vol. 111, no. 10, pp. 1927-1939. https://doi.org/10.1152/jn.00631.2013
Gaier, E. D. ; Rodriguiz, R. M. ; Zhou, J. ; Ralle, Martina ; Wetsel, W. C. ; Eipper, B. A. ; Mains, R. E. / In vivo and in vitro analyses of amygdalar function reveal a role for copper. In: Journal of Neurophysiology. 2014 ; Vol. 111, No. 10. pp. 1927-1939.
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