Dorsal raphe serotonin neurons in mice: Immature hyperexcitability transitions to adult state during first three postnatal weeks suggesting sensitive period for environmental perturbation

Benjamin D. Rood, Lyngine H. Calizo, David Piel, Zachary P. Spangler, Kaitlin Campbell, Sheryl G. Beck

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Trauma during early life is a major risk factor for the development of anxiety disorders and suggests that the developing brain may be particularly sensitive to perturbation. Increased vulnerability most likely involves altering neural circuits involved in emotional regulation. The role of serotonin in emotional regulation is well established, but little is known about the postnatal development of the raphe where serotonin is made. Using whole-cell patch-clamp recording and immunohistochemistry, we tested whether serotonin circuitry in the dorsal and median raphe was functionally mature during the first 3 postnatal weeks in mice. Serotonin neurons at postnatal day 4 (P4) were hyperexcitable. The increased excitability was due to depolarized resting membrane potential, increased resistance, increased firing rate, lack of 5-HT1A autoreceptor response, and lack ofGABAsynaptic activity. Over the next 2 weeks,membraneresistance decreased and resting membrane potential hyperpolarized due in part to potassium current activation. The 5-HT1A autoreceptor-mediated inhibition did not develop until P21. The frequency of spontaneous inhibitory and excitatory events increased as neurons extended and refined their dendritic arbor. Serotonin colocalized with vGlut3 at P4 as in adulthood, suggesting enhanced release of glutamate alongside enhanced serotonin release. Because serotonin affects circuit development in other brain regions, altering the developmental trajectory of serotonin neuron excitability and release could have many downstream consequences. We conclude that serotonin neuron structure and function change substantially during the first 3 weeks of life during which external stressors could potentially alter circuit formation.

Original languageEnglish (US)
Pages (from-to)4809-4821
Number of pages13
JournalJournal of Neuroscience
Volume34
Issue number14
DOIs
StatePublished - 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'Dorsal raphe serotonin neurons in mice: Immature hyperexcitability transitions to adult state during first three postnatal weeks suggesting sensitive period for environmental perturbation'. Together they form a unique fingerprint.

Cite this