Early- and Late-Born Parvalbumin Basket Cell Subpopulations Exhibiting Distinct Regulation and Roles in Learning

Abstract

Brain networks can support learning by promoting acquisition of task-relevant information or by adhering to validated rules, but the mechanisms involved are poorly understood. Upon learning, local inhibitory parvalbumin (PV)-expressing Basket cell networks can switch to opposite configurations that either favor or interfere with further learning, but how this opposite plasticity is induced and relates to distinct learning requirements has remained unclear. Here, we show that PV Basket cells consist of hitherto unrecognized subpopulations, with distinct schedules of neurogenesis, input connectivities, output target neurons, and roles in learning. Plasticity of hippocampal early-born PV neurons was recruited in rule consolidation, whereas plasticity of late-born PV neurons was recruited in new information acquisition. This involved regulation of early-born neuron plasticity specifically through excitation, and of late-born neuron plasticity specifically through inhibition. Therefore, opposite learning requirements are implemented by distinct local networks involving PV Basket cell subpopulations specifically regulated through inhibition or excitation.

Regulation of Parvalbumin Basket cell plasticity in rule learning

“…Likewise, only lateborn cells exhibited a corresponding Mef2a/inhibitory connectivity shift upon pharmacogenetic inhibition. These results provided evidence that persistent direct non-synaptic excitation or inhibition of PV neurons can shift PV expression values in all PV cells, but only early-born neurons exhibit Mef2a/connectivity plasticity upon excitation and only late-born neurons exhibit Mef2a/connectivity plasticity upon inhibition [22].…”

“…In complementary experiments tdTomato-positive E11.5 donor PV neurons transplanted into an E13.5 host exhibited high-and intermediate-high PV neurons values characteristic of their birthdate in donor E11.5 embryo. We concluded that PV and excitation/inhibition connectivity profiles of early-and late-born PV neurons in the adult reflect distinct intrinsic properties of these neurons determined at the time of neurogenesis [22].…”

“…Hippocampal PV neurons generated at E9.5 or E11.5 were predominantly high-and intermediate-high PV, whereas neurons generated at E13.5 or E15.5 were predominantly intermediate-lowand low-PV [22].…”

“…Furthermore, in DG cFC specifically induced a reduction in excitatory synaptic puncta onto early-born PV cells, and EE specifically induced a reduction in inhibitory synaptic puncta onto late-born PV cells. Therefore, both in CA3/CA1 and in DG early-born PV neuron cell-plasticity specifically involved changes in excitatory connectivity onto PV neurons, whereas lateborn cell-plasticity specifically involved changes in inhibitory connectivity onto PV neurons [22].…”

Developmental Age Differentially Mediates the Calcium-Binding Protein Parvalbumin in the Rat: Evidence for a Selective Decrease in Hippocampal Parvalbumin Cell Counts

“…Of note, Takesian and Hensch [15] have argued that the onset of critical periods in sensory and association cortices is determined by maturation of GABAergic circuits that regulate the developmental organization of neocortical, as well as HPC, circuits. Strong evidence supporting a specific role for PV - minimally as a biological marker of the state of GABAergic circuit functioning - has been provided in elegant studies conducted by Donato et al [29,70]. These studies have indicated that select populations of CA1 PV+ basket cells (both early- and late-born) differentially increase PV, which is dependent upon distinct learning requirements in mice.…”