Fast-spiking, parvalbumin+ GABAergic interneurons: From cellular design to microcircuit function

H. Hu, J. Gan, P. Jonas
2014 Science  
The success story of fast-spiking, parvalbumin-expressing (PV + ) GABAergic interneurons is amazing. In 1995, the properties of these interneurons were completely unknown. 20 years later, thanks to the massive use of subcellular patchclamp techniques, simultaneous multiple-cell recording, optogenetics, in vivo measurements, and computational approaches, our knowledge about PV + interneurons became more extensive than for several types of pyramidal neurons (Box 1). These findings have
more » ... ngs have implications beyond the "small world" of basic research on GABAergic cells. For example, the results provide a first proof of principle that neuroscientists might be able to close the gaps between molecular, cellular, network, and behavioral level, which represents one of the main challenges at the present time. Furthermore, the results may form the basis for using PV + interneurons as therapeutical targets for brain diseases in the future. However, much needs to be learned about the basic function of these interneurons before clinical neuroscientists will be able to use PV + interneurons for therapeutic purposes. developmental trajectory of cortical PV + interneurons, which are born in the medial ganglionic eminence and depend on specific sets of transcription factors (i.e. Nkx2-1 and Lhx6), may be exploited for labeling (13) (14) (15) . In the present review, we will summarize our current knowledge about fastspiking, PV + interneurons at the molecular, cellular and network level. We concentrate on basket cells (the classical PV + interneurons), but include information about axo-axonic cells or other types of GABAergic interneurons also expressing PV (5; Box 2). Furthermore, we focus on the hippocampus and the neocortex. For in vitro analysis of PV + interneurons, the advantages of the hippocampus are evident, especially the clearly defined layering and the availability of elaborate classification schemes (5). For in vivo analysis, the advantages of the neocortex become apparent, including the superficial localization of cells in the brain and the opportunity to easily define adequate behavioral stimuli. Morphological properties and connectomics of PV + interneurons How can we understand the function of PV + interneurons at the molecular, cellular and network level? Following Francis Crick's statement "If you want to understand function, study structure" (16), let us first take a look at the structure of PV + interneurons, particularly their input domains, the dendrites, and their output domains, the axons. The morphological properties of the dendrites of PV + interneurons are remarkable in several ways (1). PV + interneurons have multiple dendrites which often cross layers (17) (18) (19) (20) . This will permit PV + interneurons to receive input from different afferent pathways, such as feedforward and feedback pathways. The cumulative dendritic length of single PV + interneurons ranges from 3.1 to 9 mm (17-20). Long dendrites allow PV + interneurons to sample input from a large population of principal cells. Finally, somata and dendrites of PV + interneurons are densely covered with synapses. PV + interneurons in the hippocampal CA3 or CA1 region have ~16000-34000 synapses, 94% of which are excitatory and 6% are inhibitory (17, 20) . A large proportion of inhibitory synapses is PV + (17), but inhibitory inputs from vasoactive intestinal peptide-and somatostatin-expressing interneurons are also present (21, 22) . Thus, PV + interneurons receive convergent excitatory input from principal neurons, and inhibitory input primarily from other PV + interneurons. Because the dendrites of PV + interneurons are largely aspiny, excitatory synapses are formed on dendritic shafts. This may facilitate the generation of fast excitatory postsynaptic potentials (EPSPs; 23). The morphological properties of the axon of PV + interneurons are also intriguing (1). In the classical anatomical literature, GABAergic interneurons were sometimes referred to as "short axon" cells. However, for many PV + interneurons, this seems entirely incorrect. The axon shows extensive arborization, and the cumulative axonal length of single PV + interneurons is 30-50 mm (33 mm in the dentate gyrus, 18; 46 mm in the hippocampal CA1 region, 24; 20 and 24 mm in the frontal cortex, 25).
doi:10.1126/science.1255263 pmid:25082707 fatcat:shd26tccineyxh47xul5djur2a