Transcriptional and morphological profiling of parvalbumin interneuron subpopulations in the mouse hippocampus

Abstract

The diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.

Inhibitory control in neuronal networks relies on the extracellular matrix integrity

“…Neuronal types were discriminated against by their spiking behavior and resting membrane potentials. Like in previous studies [46,57,68], the inhibitory interneurons exhibited considerably faster spiking dynamics (spiking frequency ≥ 5 Hz) than the excitatory neurons (spiking frequency below 5 Hz). ECM depletion significantly increased the spiking frequency of inhibitory interneurons but did not alter action potential threshold, resting membrane potential, and capacitance (Fig.…”

Neurexin-3 defines synapse- and sex-dependent diversity of GABAergic inhibition in ventral subiculum

“…Both male and female PVs exhibited high overall levels of Nrxn1 and Nrxn3 and relatively low levels of Nrxn2 expression. High levels of Nrxn1 were unexpected, as other groups have reported Nrxn3 to be the most abundant Nrxn in CA1 PV cells (Nguyen et al, 2016;Que et al, 2021). This led us to investigate the expression of Nrxn isoforms in vSUB PV neurons (Figure 7D).…”

Hippocampal gamma and sharp-wave ripple oscillations are altered in a Cntnap2 mouse model of autism spectrum disorder

“…For example, changes in unitary connections between inhibitory neurons and pyramidal cells, or changes in release probability at inhibitory synapses, could contribute to the observed alterations in hippocampal oscillations. In addition, PV+ interneurons include a subpopulation of interneurons such as basket, axoaxonic, and bistratified neurons with different morphological features (Que et al, 2021) and potentially distinct sub-roles in the overall modulation of network dynamics (Forro et al, 2015). As information emerges on the functional roles of distinct subpopulations of PV+ interneurons (and the experimental tools necessary to selectively manipulate these subpopulations), it will be interesting to study these possibilities in further detail.…”

“…In the hippocampus, a PV-positive interneuron subpopulation, which includes further subtypes such as basket cells, axoaxonic cells, and bistratified neurons (Que et al, 2021), primarily innervate the soma and proximal dendrites of excitatory pyramidal neurons (Miles et al, 1996). These neurons represent a subset ($25%) of the total interneuron population (Kosaka et al, 1987), derive from progenitor cells in a subpallial embryonic region designated the medial ganglionic eminence (MGE) (Gelman and Marı ´n, 2010), and can make connections with up to 1,000 pyramidal cells (Bezaire and Soltesz, 2013;Li et al, 1992).…”

“…Hippocampal PV-positive interneurons are also essential for timing and spatial pyramidal cell synchrony during sharp wave ripples (SWRs) thought to play a role during navigation and memory consolidation (Buzsa ´ki, 2015). Indeed, numerous studies suggest that PV-positive basket cell activity is phaselocked to ripple cycles (Ylinen et al, 1995;Klausberger et al, 2003;Ra ´cz et al, 2009;Varga et al, 2012), and more importantly, activation of these interneurons can induce coherent ensemble spiking in pyramidal cells (Stark et al, 2014). Critically, these studies suggest an essential role for a sub-class of interneurons (e.g., PV-expressing fast-spiking interneurons) in dynamically regulating the E/I balance during normal network processing.…”