Feature Finding Title
Feature Finding Figure
Deficits in cognitive control, a core disturbance of schizophrenia, appear to emerge from impaired prefrontal gamma oscillations. Cortical gamma oscillations require strong inhibitory inputs to pyramidal neurons from the parvalbumin basket cell (PVBC) class of GABAergic neurons. Recent findings indicate that schizophrenia is associated with multiple pre- and post-synaptic abnormalities in PVBCs, each of which weakens their inhibitory control of pyramidal cells. These findings suggest a new model of cortical dysfunction in schizophrenia in which PVBC inhibition is decreased to compensate for an upstream deficit in pyramidal cell excitation. The figure illustrates connectivity between pyramidal (P) neurons and PVBC and chandelier (PVChC) cells in DLPFC layer 3. Reciprocal connections formed by the local axon collaterals of pyramidal neurons provide recurrent excitation, whereas the excitatory inputs from pyramidal neurons to PV basket cells furnish feedback inhibition. These connections are critical for generating gamma band oscillations, and the strengths of these connections are adjusted to maintain normal E/I balance in the healthy brain (top). In schizophrenia, lower spine density in layer 3 pyramidal neurons is hypothesized to result in lower network excitation, evoking a compensatory reduction in feedback inhibition of pyramidal neurons from PVBCs (less presynaptic GAD67; fewer postsynaptic GABAA a1 receptors) and increased depolarization of pyramidal neurons by PVChs (less presynaptic GABA membrane transporter 1; more postsynaptic GABAA a2 receptors). This compensation is thought to re-balance cortical excitation and inhibition, but at a level of each that is insufficient to generate the gamma oscillation power required for high levels of cognitive control.

Lewis DA, Curley AA, Glausier JR, Volk DW: Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci 35:57-67, 2012.

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