@article {TikhonovaENEURO.0208-18.2018, author = {Tatiana B. Tikhonova and Takeaki Miyamae and Yelena Gulchina and David A. Lewis and Guillermo Gonzalez Burgos}, title = {Cell type- and layer-specific muscarinic potentiation of excitatory synaptic drive onto parvalbumin neurons in mouse prefrontal cortex}, elocation-id = {ENEURO.0208-18.2018}, year = {2018}, doi = {10.1523/ENEURO.0208-18.2018}, publisher = {Society for Neuroscience}, abstract = {Cholinergic neuromodulation is thought to shape network activity in the prefrontal cortex (PFC), and thus PFC-dependent cognitive functions. Acetylcholine (ACh) may modulate the activity of parvalbumin-positive (PV+) neurons, which critically regulate cortical network function. However, the mechanisms of cholinergic regulation of PV+ neuron activity, and particularly of the basket (BC) versus chandelier (ChC) subtypes, are unclear.Using patch clamp recordings in acute slices, we examined the effects of the ACh receptor (AChR) agonist carbachol on the excitatory synaptic drive onto BCs or ChCs in layers 2 to 6 of mouse PFC. Carbachol increased the frequency and amplitude of spontaneous excitatory synaptic currents (sEPSCs) recorded from PV+ BCs in layers 3-6, but not in BCs from layer 2. Moreover, carbachol did not change the sEPSCs in ChCs, which were located exclusively in layer 2. The potentiation of sEPSCs in layers 3-6 BCs was prevented by the Na+ channel blocker tetrodotoxin and was abolished by the M1-selective muscarinic AChR antagonist pirenzepine. Thus, carbachol potentiates the activity-dependent excitatory drive onto PV+ neurons via M1-muscarinic AChR activation in a cell type- and layer-specific manner. In current clamp recordings with synaptic transmission blocked, carbachol directly evoked firing in deep layer pyramidal neurons (PNs). In contrast, carbachol elicited deep layer BC firing indirectly, via glutamate-mediated synaptic drive.Our data suggest that ACh powerfully regulates PFC microcircuit function by facilitating the firing of pyramidal neurons that synaptically recruit deep layer PV+ BC activity, possibly shaping the patterns of network activity that contribute to cognitive function.Significance Statement Cholinergic neuromodulation and parvalbumin-positive (PV+) neurons may be essential for regulation of prefrontal cortex (PFC) network activity. To determine whether cholinergic input modulates PFC network function via PV+ neurons, we examined the effects of the cholinergic agonist carbachol on the excitatory synaptic drive onto PV+ neurons in mouse PFC. Carbachol, via M1 muscarinic receptor activation, potentiated the excitatory synaptic currents onto PV+ basket cells in deep cortical layers, but not onto superficial layer basket or chandelier cells. Carbachol directly elicited firing in deep layer pyramidal neurons but basket cell activity was recruited indirectly, via synaptic glutamate-mediated excitatory drive. Our data suggest that cholinergic neuromodulation contributes to PFC-dependent cognitive function recruiting PV+ neuron activity in a cell type- and layer-specific manner.}, URL = {https://www.eneuro.org/content/early/2018/10/31/ENEURO.0208-18.2018}, eprint = {https://www.eneuro.org/content/early/2018/10/31/ENEURO.0208-18.2018.full.pdf}, journal = {eNeuro} }