Radial Glial Lineage Progression and Differential Intermediate Progenitor Amplification Underlie Striatal Compartments and Circuit Organization

Abstract

The circuitry of the striatum is characterized by two organizational plans: the division into striosome and matrix compartments, thought to mediate evaluation and action, and the direct and indirect pathways, thought to promote or suppress behavior. The developmental origins of these organizations and their developmental relationships are unknown, leaving a conceptual gap in understanding the cortico-basal ganglia system. Through genetic fate mapping, we demonstrate that striosome-matrix compartmentalization arises from a lineage program embedded in lateral ganglionic eminence radial glial progenitors mediating neurogenesis through two distinct types of intermediate progenitors (IPs). The early phase of this program produces striosomal spiny projection neurons (SPNs) through fate-restricted apical IPs (aIPs) with limited capacity; the late phase produces matrix SPNs through fate-restricted basal IPs (bIPs) with expanded capacity. Notably, direct and indirect pathway SPNs arise within both aIP and bIP pools, suggesting that striosome-matrix architecture is the fundamental organizational plan of basal ganglia circuitry.

Dynamic postnatal development of the cellular and circuit properties of striatal D1 and D2 spiny projection neurons

“…Moreover, we show that many of the properties of mature D1 and D2 SPNs are already apparent by the first and second postnatal weeks, which is thought to be a period prior to much exploratory motor behaviour (Dehorter et al 2011) or exposure to structured input from the sensory periphery (Tobach et al 1971;Krug et al 2001;Akerman et al 2002;Ko et al 2013;Mowery et al 2015Mowery et al , 2016Mowery et al , 2017. This is consistent with the idea that neuronal specification can occur early in development (Lobo et al 2006(Lobo et al , 2008Arlotta et al 2008;Ehrman et al 2013;Lu et al 2014;Zhang et al 2016;Merchan-Sala et al 2017;Kelly et al 2018;Tinterri et al 2018;Xu et al 2018) with further postnatal development guided by, for example, neural activity (Zhang & Poo, 2001;Kozorovitskiy et al 2012;Peixoto et al 2016) and neuromodulation (Kozorovitskiy et al 2015;Lieberman et al 2018). Future work will be able to clarify the precise interaction of these factors during striatal development as well as their differential involvement in neurodevelopmental disorders (Graybiel & Rauch, 2000;Del Campo et al 2011;Langen et al 2011;McNaught & Mink, 2011;Shepherd, 2013;Albin, 2018).…”

“…However, some differences were observed. Initially, the size and duration of the action potentials were more mature for the D1 SPNs, possibly as a result of their J Physiol 597.21 suggested earlier birthdate (Marchand & Lajoie, 1986;van der Kooy & Fishell, 1987;Kelly et al 2018). Secondly, many of the differences in the electrical properties of SPNs, such as the comparatively more depolarized resting membrane potential, higher input resistance and higher firing frequencies of D2 SPNs, are already apparent in the second postnatal week and are maintained into adulthood (Gertler et al 2008;Peixoto et al 2016;Lieberman et al 2018).…”

“…These initial gap junctions could facilitate synchronization of SPN activity (Venance et al 2004;Hestrin & Galarreta, 2005) and the establishment of synaptic connections (Yu et al 2012). The first inhibitory synaptic connections were detected in the first postnatal week coming from D1 SPNs only, potentially a reflection of their earlier birthdate (Marchand & Lajoie, 1986;van der Kooy & Fishell, 1987;Kelly et al 2018), but in J Physiol 597.21 the second postnatal week both D1 and D2 SPNs form inhibitory synaptic connections with each other. Interestingly, the relative biases in connectivity (e.g.…”

Compartmental function and modulation of the striatum

“…Striatal cells migrate from the lateral ganglionic eminence in two distinct waves, beginning around embryonic days 9.5-13.5 in rodents (Kelly et al, 2018;Tinterri et al, 2018). In fact, striosomes represent some of the oldest and earliest assembled circuit components in the striatum.…”

“…In fact, striosomes represent some of the oldest and earliest assembled circuit components in the striatum. Striatal cells migrate from the lateral ganglionic eminence in two distinct waves, beginning around embryonic days 9.5-13.5 in rodents (Kelly et al, 2018;Tinterri et al, 2018). The cells in the first wave ultimately correspond to striosomal SPNs and migrate to their destinations around the same time as the earliest cortical (Layer 6) neurons do, putting them in position to receive early corticostriatal as well as early thalamostriatal inputs (Fishell & van der Kooy, 1987;…”