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.

Balanced feedforward inhibition and dominant recurrent inhibition in olfactory cortex

“…Intracortical excitation recruits a number of interneuron classes within L2/3 that, in turn, provide recurrent inhibition to principal neurons (20,24,27,28). Stimulation of the LOT evokes shortlatency feedforward inhibition that targets principal neuron dendrites, as well as long-latency, recurrent inhibition that is somatic (24,28,29). These findings are consistent with the different laminar locations of inhibitory interneurons mediating feedforward and recurrent inhibition respectively.…”

“…Principal excitatory neurons are found in layer (L) 2/3 and send dendrites to L1, where they receive odor-related excitation directly from the olfactory bulb via the lateral olfactory tract (LOT) (23). LOT afferents also drive horizontal and neurogliaform inhibitory interneurons within L1, yielding feedforward inhibition of principal neurons (24). Within the cortex, principal neurons send axon collaterals throughout L2/3 and to an intracortical fiber tract in L1b (25,26).…”

“…Within the cortex, principal neurons send axon collaterals throughout L2/3 and to an intracortical fiber tract in L1b (25,26). Intracortical excitation recruits a number of interneuron classes within L2/3 that, in turn, provide recurrent inhibition to principal neurons (20,24,27,28). Stimulation of the LOT evokes shortlatency feedforward inhibition that targets principal neuron dendrites, as well as long-latency, recurrent inhibition that is somatic (24,28,29).…”

Cortical Evolution: Introduction to the Reptilian Cortex

“…Afferent synapses impinge on both layer-1 interneurons and on distal dendrites of layer-2 pyramidal cells; interneurons provide both feed-forward and feedback inhibition to pyramidal cells that themselves provide recurrent excitation to other pyramidal neurons (Smith et al 1980;Bekkers 2011, 2012;Kriegstein and Connors 1986;Mancilla et al 1998). In both PCx and DCx, superficial layer-1 interneurons tend to receive a higher density of afferent input than pyramidal cells do (Smith et al 1980;Suzuki and Bekkers 2012;Stokes and Isaacson 2010), which, combined with a strong feed-back inhibition via layer-2/3 interneurons (Suzuki and Bekkers 2012;Kriegstein and Connors 1986;Stokes and Isaacson 2010) may explain the observed strong inhibition evoked by sensory stimulation and the sparseness of pyramidal cell firing. To a first degree, PCx and DCx thus have a similar microcircuit layout: both exhibit distal dendritic excitation from sensory afferents, strong feed-forward inhibition, recurrent excitation through the so-called associational intracortical connections, and feedback inhibition (Haberly 2001;Shepherd 2011).…”

“…Horizontal and neurogliaform interneurons in layer 1 receive afferent inputs from the LOT and mediate fast feed-forward inhibition targeting apical dendrites of layer-2 pyramidal cells. Bitufted, fast-spiking and regular spiking interneurons from layers 2 and 3 receive very little direct afferent input from the LOT but provide strong feedback inhibition onto the somata and basal dendrites of pyramidal cells (Suzuki and Bekkers 2012;Stokes and Isaacson 2010). Similarly, different populations of inhibitory interneurons in turtle DCx subserve mainly feed-forward (subpial cells; Mancilla et al 1998) or feedback (Mancilla et al 1998;Connors and Kriegstein 1986) inhibition.…”