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Opiate dependence induces cell type-specific plasticity of intrinsic membrane properties in the rat juxtacapsular bed nucleus of stria terminalis (jcBNST)

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Abstract

Rationale

Drugs of abuse can alter circuit dynamics by modifying synaptic efficacy and/or the intrinsic membrane properties of neurons. The juxtacapsular subdivision of the bed nucleus of stria terminalis (jcBNST) has unique connectivity that positions it to integrate cortical and amygdala inputs and provide feed-forward inhibition to the central nucleus of the amygdala (CeA), among other regions. In this study, we investigated changes in the synaptic and intrinsic properties of neurons in the rat jcBNST during protracted withdrawal from morphine dependence using a combination of conventional electrophysiological methods and the dynamic clamp technique.

Results

A history of opiate dependence induced a form of cell type-specific plasticity characterized by reduced inward rectification associated with more depolarized resting membrane potentials and increased membrane resistance. This cell type also showed a lower rheobase when stimulated with direct current (DC) pulses as well as a decreased firing threshold under simulated synaptic bombardment with the dynamic clamp. Morphine dependence also decreased excitatory postsynaptic potential amplification, suggesting the downregulation of the persistent Na+ current (I NaP).

Conclusion

These findings show that a history of morphine dependence leads to persistent cell type-specific plasticity of the passive membrane properties of a jcBNST neuronal population, leading to an overall increased excitability of such neurons. By altering the activity of extended amygdala circuits where they are embedded, changes in the integration properties of jcBNST neurons may contribute to emotional dysregulation associated with drug dependence and withdrawal.

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Abbreviations

BLA:

Basolateral nucleus of amygdala

BNST:

Bed nucleus of stria terminalis

sEPSC:

Spontaneous excitatory postsynaptic current

EPSP:

Excitatory postsynaptic potential

I KIR :

Inward-rectifying K+ current

I NaP :

Persistent Na+ current

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Acknowledgements

This work was supported by National Institutes of Health grants DA031566, DA043268 and the Hungarian National Brain Research Program grant KTIA_NAP_13-2014-0018.

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Author notes

  1. Walter Francesconi and Attila Szücs contributed equally.

Authors and Affiliations

  1. Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA

    Walter Francesconi

  2. Department of Anatomy and Cell Biology, School of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    Walter Francesconi & Fulvia Berton

  3. BioCircuits Institute, University of California San Diego, La Jolla, CA, USA

    Attila Szücs

  4. MTA-ELTE NAP-B Neuronal Cell Biology Group, Eötvös Lóránd University, Budapest, Hungary

    Attila Szücs

  5. Dipartimento di Biologia, Universita’ degli Studi di Pisa, Pisa, Italy

    Fulvia Berton

  6. Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA

    George F. Koob & Leandro F. Vendruscolo

  7. National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA

    George F. Koob

  8. National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA

    Leandro F. Vendruscolo

  9. Department of Immunology and Microbiology and Department ofNeuroscience, The Scripps Research Institute, La Jolla, CA, USA

    Pietro Paolo Sanna

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  1. Walter Francesconi
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  2. Attila Szücs
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  3. Fulvia Berton
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  4. George F. Koob
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  6. Pietro Paolo Sanna
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Correspondence to Pietro Paolo Sanna.

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Francesconi, W., Szücs, A., Berton, F. et al. Opiate dependence induces cell type-specific plasticity of intrinsic membrane properties in the rat juxtacapsular bed nucleus of stria terminalis (jcBNST). Psychopharmacology 234, 3485–3498 (2017). https://doi.org/10.1007/s00213-017-4732-4

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