New dimensions of interneuronal specialization unmasked by principal cell heterogeneity

Abstract

While the diversity of neocortical and hippocampal GABAergic interneurons is recognized in terms of their anatomical, molecular, and functional properties, principal cells are usually assumed to constitute homogenous populations. However, even within a single layer, subpopulations of principal cells can often be differentiated by their distinct long-range projection targets. Such subpopulations of principal cells can have different local connection properties and excitatory inputs, forming subnetworks that may serve as separate information-processing channels. Interestingly, as reviewed here, recent evidence has revealed specific instances where interneuron cell types selectively innervated distinct subpopulations of principal cells, targeting only those with particular long-distance projection targets. This organization represents a novel form of interneuron specialization, providing interneurons with the potential to selectively regulate specific information-processing streams.

Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons

“…This leads to the conclusion that target selection by INs occurs at the single neuron level, and provides evidence that PNs can, at least in part, guide the establishment of their afferent inhibitory synapses. This supports the theory that INs may be able to selectively modulate only certain PNs even if they are physically intermingled (Krook-Magnuson et al, 2012; Lee et al, 2014; Varga et al, 2010). …”

“…Different populations of PNs within L5 receive differing excitatory and inhibitory inputs, and emerging evidence suggests that the strength of inhibition from PV + cells varies between PN subtypes in L5 (Lee et al, 2014). Similarly, INs selectively innervate PNs with distinct long-distance targets (Krook-Magnuson et al, 2012; Lee et al, 2014; Varga et al, 2010). Together, these results suggest that PN identity might have a role in the establishment of specific afferent connectivity.…”

Heterogeneity in hippocampal place coding

“…nucleus accumbens or amygdala) exhibit pronounced variation in gene expression [30 •• ]. This is especially intriguing in light of work showing that different classes of interneurons target specific CA1 subpopulations that differ in their outputs [73]. Thus, the long-range output targeting of hippocampal cells presents another feature that may vary together with afferent inputs, local inhibitory circuitry and genetic and biophysical profiles to define unique and possibly independent functional neuronal subpopulations (Figure 3).…”

Beyond the hammer and the scalpel: selective circuit control for the epilepsies

“…While the finding that broadly increasing the excitation of excitatory neurons can result in seizures is not entirely surprising, this study does show that CNO delivery itself need not be anti-ictogenic, and that results will critically depend upon the type of modulation. Future use of such technology can expand on these findings, for example attempting to better parse the role of specific neuronal populations, including subpopulations of excitatory neurons in focal cortical seizures 31–33 .…”