Feature Finding Title
Featured Finding Figure
Synchronization of neuronal activity in the neocortex may underlie the coordination of neural representations and is thus critical for optimal cognitive function. Because cognitive deficits are the major determinant of functional outcome in schizophrenia, identifying their neural basis is important for the development of new therapeutic interventions. Substantial data suggest that phasic synaptic inhibition mediated by specific subtypes of cortical GABA neurons is essential for the production of synchronized network oscillations. As illustrated in the figure, GABA neurons are efficient at synchronizing neuronal activity in cortical networks. A) Top: A local field potential (LFP) recorded with an extracellular electrode in the vicinity of the pyramidal neurons reflects the synchronization of pyramidal cell activity. Note the negative (downward) components of the LFP, roughly coincident with the periods of spike synchronization recorded simultaneously, as shown in the traces below. Bottom: Superimposed traces of intracellular membrane potential recording, illustrating how the asynchronous firing of pyramidal neurons in response to continuous excitatory drive becomes transiently synchronized by phasic synaptic inhibition. Stimulation of an inhibitory input at the times indicated by the black arrows produces hyperpolarizing IPSPs that transiently inhibit spike firing and produce nearly synchronous spikes shortly after the IPSPs end. B) Diagram indicating that the axon of an individual GABA neuron makes multiple synaptic contacts onto multiple postsynaptic pyramidal cells and also onto other GABA neurons. The proportion of postsynaptic target cells (3 pyramidal: 1 GABA) reflected in the diagram matches the abundance of cells in real circuits. However, certain interneuron subtypes display marked target selectivity. Alterations in GABA neurotransmission in schizophrenia can decrease the strength of inhibitory connections in a cell-type specific manner and contribute to altered neural synchrony and impaired cognitive function in schizophrenia, suggesting that interventions aimed at augmenting the efficacy of GABA neurotransmission might be of therapeutic value.
Gonzalez-Burgos G, Lewis DA: GABA neurons and the mechanisms of network oscillations: Implications for understanding cortical dysfunction in schizophrenia. Schizophr Bull 34: 944-961, 2008.

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