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Postnatal development of chandelier neuron inputs to pyramidal neurons in monkey DLPFC

The axon terminals of chandelier neurons are vertical arrays of boutons (cartridges) that are immunoreactive for parvalbumin (PV) or GABA membrane transporter 1 (GAT1), and outline the axon initial segment of pyramidal neurons. Although the developmental time course differs somewhat for these two markers, as illustrated in the schematic summary, the density of labeled cartridges is low in the DLPFC of newborn monkeys, increases to reach a peak before the onset of puberty, and then declines markedly during adolescence (shaded area between 15 and 42 months of age) to adult levels (Cruz et al 2003). These density changes in PV- and GAT-immunoreactive cartridges seem to reflect developmental shifts in the concentration of these proteins (and thus in the detectability of cartridges) as cartridges are readily visualized with the Golgi technique over this same time period. Interestingly, the peak and subsequent decline in the density of labeled cartridges occurs prior to the age when the peak density of PV-immunoreactive varicosities, putative axon terminals from the wide arbor class of PV-expressing GABA neurons, is achieved. Postsynaptically, the detectability of the a2-subunit of the GABAA receptor in pyramidal neuron axon initial segments is high at birth, and then markedly declines during adolescence before stable adult levels are achieved.
The marked developmental changes in these pre- and postsynaptic markers of inhibition at the inputs from chandelier and wide arbor cells to the perisomatic region of pyramidal neurons indicate that the capacity to synchronize pyramidal neuron output in the DLPFC might be in substantial flux until adulthood. Consequently, the protracted developmental time course of improvements in performance on working memory tasks might depend on both refinements in the number of excitatory connections among pyramidal neurons and changes in their proximal inhibitory inputs. These developmental changes during adolescence might contribute to unmasking the consequences of inherited abnormalities in the regulation of GABAergic neurotransmission and might help explain why certain life experiences during adolescence (for example, stress or cannabis exposure) seem to increase the risk for schizophrenia.

References
Cruz DA, Eggan SM, Lewis DA (2003): Postnatal development of pre- and post-synaptic GABA markers at chandelier cell inputs to pyramidal neurons in monkey prefrontal cortex. J Comp Neurol 465:385-400.

Lewis DA, Hashimoto T, Volk DW: Cortical inhibitory neurons and schizophrenia. Nature Reviews Neuroscience 6: 312-324, 2005.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
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