The International Journal of Neuropsychopharmacology

Research Article

Neonatal rearing conditions distinctly shape locus coeruleus neuronal activity, dendritic arborization, and sensitivity to corticotrophin-releasing factor

Jerome D. Swinnya1, Eimear O'Farrella1, Brian C. Binghama2, David A. Piela1, Rita J. Valentinoa1 c1* and Sheryl G. Becka1*

a1 Department of Anesthesiology, Children's Hospital of Philadelphia, PA, USA

a2 Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA

Abstract

Early life events influence vulnerability to psychiatric illness. This has been modelled in rats and it has been demonstrated that different durations of maternal separation shape adult endocrine and behavioural stress reactivity. One system through which maternal separation may act is the locus coeruleus (LC)–norepinephrine system that regulates emotional arousal. Here we demonstrate that different durations of maternal separation have distinct effects on LC physiology and dendritic morphology. Rat pups were separated from the dam for 15 min/d (HMS-15) or 180 min/d (HMS-180) from post-natal days 2–14. Others were either undisturbed (HMS-0) or were vendor-purchased controls. LC characteristics were compared at age 22–35 d using whole-cell recordings in vitro. Cells were filled with biocytin for morphological analysis. LC neurons of HMS-180 rats were tonically activated compared to HMS-15 and control rats, with firing rates that were 2-fold higher than these groups. Corticotrophin-releasing factor (CRF) application did not further activate LC neurons of HMS-180 rats but increased LC firing rate in HMS-0 and control rats. LC neurons of HMS-15 rats were resistant to excitation by CRF. Maternal separation also affected LC dendritic morphology. LC dendrites of HMS-15 rats exhibited less branching and decreased total dendritic length, an effect that could decrease the probability of contacting limbic afferents that terminate in the pericoerulear region. This effect may provide a structural basis for an attenuated magnitude of emotional arousal. Together, these results demonstrate long-term consequences of early life events on the LC–norepinephrine system that may shape adult behaviour.

(Received April 10 2009)

(Reviewed May 15 2009)

(Revised June 27 2009)

(Accepted June 30 2009)

(Online publication August 05 2009)

Correspondence:

c1 Address for correspondence: R. J. Valentino, Ph.D., 3615 Civic Center Boulevard, ARC room 402A, Philadelphia, PA 19104, USA. Tel.: 215-590-0650 Fax: 215-590-3364 Email: rjv@mail.med.upenn.edu

Footnotes

* These authors contributed equally to this work.