Postnatal development of synaptic structure proteins in pyramidal neuron axon initial segments in monkey prefrontal cortex

Dianne A. Cruz, Emily M. Lovallo, Steven Stockton, Matthew Rasband, David A. Lewis

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

In the primate prefrontal cortex (PFC), the functional maturation of the synaptic connections of certain classes of γ-aminobutyric acid (GABA) neurons is very complex. For example, the levels of both pre- and postsynaptic proteins that regulate GABA neurotransmission from the chandelier class of cortical interneurons to the axon initial segment (AIS) of pyramidal neurons undergo marked changes during both the perinatal period and adolescence in the monkey PFC. In order to understand the potential molecular mechanisms associated with these developmental refinements, we quantified the relative densities, laminar distributions, and lengths of pyramidal neuron AIS immunoreactive for ankyrin-G, βIV spectrin, or gephyrin, three proteins involved in regulating synapse structure and receptor localization, in the PFC of rhesus monkeys ranging in age from birth through adulthood. Ankyrin-G- and βIV spectrin-labeled AIS declined in density and length during the first 6 postnatal months, but then remained stable through adolescence and into adulthood. In contrast, the density of gephyrin-labeled AIS was stable until approximately 15 months of age and then markedly declined during adolescence. Thus, molecular determinants of the structural features that define GABA inputs to pyramidal neuron AIS in monkey PFC undergo distinct developmental trajectories with different types of changes occurring during the perinatal period and adolescence. In concert with previous data, these findings reveal a two-phase developmental process of GABAergic synaptic stability and GABA neurotransmission at chandelier cell inputs to pyramidal neurons that likely contributes to the protracted maturation of behaviors mediated by primate PFC circuitry.

Original languageEnglish (US)
Pages (from-to)353-367
Number of pages15
JournalJournal of Comparative Neurology
Volume514
Issue number4
DOIs
StatePublished - Jun 1 2009

Keywords

  • Ankyrin-G
  • Chandelier cell
  • GABAA receptor
  • Gephyrin
  • Working memory
  • βIV spectrin

ASJC Scopus subject areas

  • Neuroscience(all)

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