Feature Finding Figure
Cholinergic modulation of neuronal excitability and recurrent excitation-inhibition in prefrontal cortex circuits: implications for gamma oscillations

Cholinergic neuromodulation in neocortical networks is required for gamma oscillatory activity that is associated with working memory and other cognitive processes. Importantly, the cholinergic agonist carbachol (CCh) induces gamma oscillations in vitro, via mechanisms that may be shared with in vivo gamma oscillations and that are consistent with the pyramidal-interneuron-network-gamma (PING) model. In the PING model, pyramidal cells (PCs), driven by asynchronous excitatory input, recruit parvalbumin-positive fast spiking interneurons (FSNs), which then synchronize the PCs via feedback inhibition. Despite the multiple studies of gamma oscillations, the mechanisms by which cholinergic neuromodulation contributes to the production of gamma oscillations is poorly understood. We studied the effects of cholinergic modulation on various circuit components of the PING model in brain slices from mouse medial prefrontal cortex (mPFC). CCh depolarized and evoked action potential firing in a fraction of PCs and increased excitatory synaptic input onto FSNs. In synaptically-connected pairs, CCh reduced the short-term depression at FSN-PC and PC-FSN synapses, equalizing synaptic strength during repetitive presynaptic firing while reducing the unitary synaptic current amplitude (figure). Interestingly, CCh increased the firing probability per cycle when both PCs or FSNs fired in response to oscillatory inputs at gamma frequency. Combined with the equalization of synaptic strength, an increase by CCh in the fraction of neurons recruited per oscillation cycle may support oscillatory synchrony of similar strength during relatively long duration episodes such as those observed during working memory tasks, suggesting a significant functional impact of cholinergic modulation of mPFC circuit components crucial for the PING model.
Pafundo DE, Miyamae T, Lewis DA, Gonzalez-Burgos G. Cholinergic modulation of neuronal excitability and recurrent excitation-inhibition in prefrontal cortex circuits: implications for gamma oscillations. JPhysiol, 591:4725-4728, 2013.

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