Interneuron cell types are fit to function

Abstract

Understanding brain circuits begins with an appreciation of their component parts - the cells. Although GABAergic interneurons are a minority population within the brain, they are crucial for the control of inhibition. Determining the diversity of these interneurons has been a central goal of neurobiologists, but this amazing cell type has so far defied a generalized classification system. Interneuron complexity within the telencephalon could be simplified by viewing them as elaborations of a much more finite group of developmentally specified cardinal classes that become further specialized as they mature. Our perspective emphasizes that the ultimate goal is to dispense with classification criteria and directly define interneuron types by function.

Figure 1. Schematic of interneuron diversity across the brain

Within each of the distinct anatomical regions of the brain exist discrete interneuron populations. In some of these cases the paralog relationships between subtypes within specific regions are obvious (such as the fast-spiking basket cells), while in others such as the hippocampal CCK basket populations they appear to uniquely population specific structures.

Figure 2. Interneurons subtypes are generated from discrete proliferative regions within the subpallium

On the Left side of this figure we show the progressive development of the telencephalon from being an undifferentiated epithelium to being divided up into discrete proliferative zones that produce particular interneuron populations. On the Right side we show a more anatomically accurate cross-section of the progenitor zones and then for illustration show a schematic of interneuron diversity in the cortex in the top panel. Interestingly, while common proliferative zone produce the entire diversity of interneurons across all telencephalic structures, unique cell types and gene expression are seen in interneuron populations that reside in particular telencephalic structures.

Figure 3. Two faces of interneuron function

A cortical circuit from the perspective of a VIP interneuron. The recruitment of VIP interneurons is constrained by the inputs it receives. The afferents can be long-range from other cortical areas and also neuromodulatory from the dorsal raphe (DR) and nucleus basalis (NB) via ionotropic receptors. The circuit impact of VIP interneurons is constrained by its outputs. The efferents are mostly to SST interneurons and to a smaller degree to PV interneurons, which lead to the disinhibition of a functional subset of principal cells (black).

Figure 4. Coordination and flow control hypotheses of recruitment

Left, Coordination hypothesis. The bottom trace shows a local field potential representing the network state in the hippocampus. The firing of different neuron types can be described in reference the LFP, both in terms of overall activity level and phase-relationship. Right, Flow control hypothesis. The bottom arrows mark the timing of three behavioral events, exit, entry and reward. The firing of different neurons can be described in reference to these events.