Microcircuits mediating feedforward and feedback synaptic inhibition in the piriform cortex

Abstract

Local inhibition by GABA-releasing neurons is important for the operation of sensory cortices, but the details of these inhibitory circuits remain unclear. We addressed this question in the olfactory system by making targeted recordings from identified classes of inhibitory and glutamatergic neurons in the piriform cortex (PC) of mice. First, we looked for feedforward synaptic inhibition provided by interneurons located in the outermost layer of the PC, layer Ia, which is the unique recipient of afferent fibers from the olfactory bulb. We found two types of feedforward inhibition: a fast-rising, spatially restricted kind that was generated by horizontal cells, and a slow-rising, more diffuse kind generated by neurogliaform cells. Both cell types targeted the distal apical dendrites of layer II principal neurons. Next, we studied feedback synaptic inhibition in isolation by making a tissue cut across layer I to selectively remove feedforward inhibitory connections. We identified a powerful type of feedback inhibition of layer II neurons, mostly generated by soma-targeting fast-spiking multipolar cells in layer III, which in turn were driven by feedforward excitation from layer II semilunar cells. Dynamic clamp simulation of feedback inhibition revealed differential effects of this inhibition on the two main types of layer II principal neurons. Thus, our results articulate the connectivity and functions of two important classes of inhibitory microcircuits in the PC. Feedforward and feedback inhibition generated by these circuits is likely to be required for the operation of this sensory paleocortex during the processing of olfactory information.