Cell-type specificity of callosally evoked excitation and feedforward Inhibition in the prefrontal cortex

Title: Cell-type specificity of callosally evoked excitation and feedforward Inhibition in the prefrontal cortex Journal: Cell Rep.(2018) 22(3): 679-692 Link: https://doi.org/10.1016/j.celrep.2017.12.073

Comments: Cortical pyramidal neurons communicate with other brain regions through a variety of long-range projections. Callosal inputs to cerebral cortex play a main role in direct communication of two hemispheres, while the targeting and functional effects of these inputs on different projection neurons are still unclear in prefrontal cortex (PFC). This article reveals the excitation and feedforward inhibition of cortico-cortical (CC) neurons and cortico-thalamic (CT) neurons induced by callosal inputs in layer 5 of the mouse PFC.

The researchers injected AAV2-ChR2 into contralateral PFC (cPFC) to label callosal inputs and injected retrograde tracer cholera toxin subunit (CTB) into cPFC as well as ipsilateral mediodorsal thalamus (MD) to label CC and CT neurons. The results showed that labeled CC and CT neurons in layer 5 were less overlapped so that they were distinct populations. Whole-cell recording revealed that CT neurons have more extensive dendrites than CC neurons. Then, the author found that callosal inputs evoked robust excitatory postsynaptic currents (EPSCs) in CC and CT neurons, inhibitory postsynaptic currents (IPSCs) followed EPSCs. Both EPSCs and IPSCs were much stronger in CT neurons than CC neurons. Parvalbumin—expressing (PV+) interneurons and somatostatin-expressing (SOM+) participate in callosal inputs suggested by other studies. Here, PV+ and SOM+ interneurons were selectively labelled by injection Cre-dependent virus to PV-Cre or SOM-Cre mouse, and they used a specific conditional rabies virus strategy together with optogenetics prove that these interneurons receive monosynaptic glutamatergic inputs from cPFC, but PV interneurons are the primary mediators of cPFC-evoked feedforward Inhibition. The author also used conditional optogenetics combined with retrograde labeling via Cre-dependent virus to clarify that both PV and SOM interneurons evoked large IPSC at CC and CT neurons, while providing stronger input on CT neurons, suggesting the biased feedforward inhibition. Next, callosal responses recorded in current clamp was performed to further elucidate the functional effects of synaptic connections and intrinsic properties, which showed that EPSCs decays much faster at CT neurons. Interestingly, that decays have no concern with membrane potential. Those findings, indicating the distinct intrinsic properties in CT and CC neurons, were testified through isolating cPFC-evoked EPSCs. Finally, the researchers found that h-current determined intrinsic properties and took part in EPSCs. Feedforward inhibition influence on CC and CT neurons was examined by injection of excitation alone or excitation paired with inhibition, which indicated the same impact on two neuron population. Taken together, this literature revealed connectivity and intrinsic properties have profound impact on synaptic responses of pyramidal neurons.