Cortical interneurons: fit for function and fit to function? Evidence from development and evolution

Abstract

Cortical inhibitory interneurons form a broad spectrum of subtypes. This diversity suggests a division of labour, in which each cell type supports a distinct function. In the present era of optimisation-based algorithms, it is tempting to speculate that these functions were the evolutionary or developmental driving force for the spectrum of interneurons we see in the mature mammalian brain. In this study, we evaluated this hypothesis using the two most common interneuron types, parvalbumin (PV) and somatostatin (SST) expressing cells, as examples. PV and SST interneurons control the activity in the cell bodies and the apical dendrites of excitatory pyramidal cells, respectively. But was this compartment-specific inhibition indeed the function for which PV and SST cells originally evolved? Does the compartmental structure of pyramidal cells shape the diversification of PV and SST interneurons over development? To address these questions, we reviewed and reanalysed publicly available data on the development and evolution of PV and SST interneurons on one hand, and pyramidal cell morphology on the other. These data speak against the idea that the compartment structure of pyramidal cells drove the diversification into PV and SST interneurons. In particular, pyramidal cells mature late, while interneurons are likely committed to a particular fate (PV vs. SST) during early development. Moreover, comparative anatomy and single cell RNA-sequencing data indicate that PV and SST cells, but not the compartment structure of pyramidal cells, existed in the last common ancestor of mammals and reptiles. Specifically, turtle and songbird SST cells also express genes that are thought to play a role in compartment-specific inhibition in mammals. PV and SST cells therefore evolved and developed the properties that allow them to provide compartment-specific inhibition before there was selective pressure for this function. This suggests that interneuron diversity originally resulted from a different evolutionary driving force and was only later co-opted for the compartment-specific inhibition it seems to serve in mammals today.

Transcriptomic correlates of state modulation in GABAergic interneurons: A cross-species analysis

“…A similar pattern has been previously observed based on nonlinear dimensionality reduction and clustering methods (see, e.g., [6,40]). The structuring of top PCs by developmental origin and cell type is expected since cell types are defined by developmentally-activated transcription factors that coregulate batteries of proteincoding genes [78,79].…”

“…We also mapped each dataset onto the mouse data using anchor-based integration [38]. This method has been widely used in cross-species analyses (e.g., [14, 19, 39, 40]). As expected, computational integration increased the similarity among the datasets (Fig.…”

Potential Information Processing Differences in Male and Hermaphrodite Neural Networks of Caenorhabditis elegans

“…To determine the number of simulation cycles, an analysis of the neuronal connectivity between common sensory neuron and common head neuron was performed. The mean neuronal jumps between common sensory neuron and common head neuron (n = 1422) as determined by NetworkX [26] in male is 4.18 with a standard deviation of 1.103 while that of hermaphrodite is 3.51 with a standard deviation of 0.737 (Table 1, Figure 1); which is indicative of the mean number of interneurons [31]. Both the mean (t-test p-value = 3.66E-74) and variance (Fligner-Killeen test p-value = 0.0133) are statistically significant.…”