Abstract
Markers of GABA neurotransmission between chandelier neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons, are altered in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia. For example, immunoreactivity for the GABA membrane transporter (GAT1) is decreased in presynaptic chandelier neuron axon terminals, whereas immunoreactivity for the GABA~A~ receptor Ξ±2 subunit is increased in postsynaptic AIS. These alterations are most marked in cortical layers 2β3. In addition, other determinants of the function of chandelier cellβpyramidal neuron synapses, such as ankyrinβG (which regulates the recruitment of sodium channels to the AIS), are also selectively altered in superficial layer pyramidal neurons in subjects with schizophrenia. Each of these components of chandelier cellβpyramidal neuron connectivity exhibits distinctive developmental trajectories in the primate DLPFC, suggesting that disturbances in these trajectories could contribute to the pathogenesis of schizophrenia. Recent findings that inputs from neocortical chandelier neurons are excitatory provide new ideas about the role of this circuitry in the pathophysiology of cortical dysfunction in schizophrenia. Β© 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 118β127, 2011