Distinct Developmental Origins Manifest in the Specialized Encoding of Movement by Adult Neurons of the External Globus Pallidus

Paul D Dodson,Joseph T Larvin,James M Duffell,Farid N Garas,Natalie M Doig,Nicoletta Kessaris,Ian C Duguid,Rafal Bogacz,Simon J.B Butt,Peter J Magill

doi:10.1016/j.neuron.2015.03.007

Paul D Dodson, Joseph T Larvin + Show 8 more

Open Access

https://doi.org/10.1016/j.neuron.2015.03.007

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Abstract

SummaryTranscriptional codes initiated during brain development are ultimately realized in adulthood as distinct cell types performing specialized roles in behavior. Focusing on the mouse external globus pallidus (GPe), we demonstrate that the potential contributions of two GABAergic GPe cell types to voluntary action are fated from early life to be distinct. Prototypic GPe neurons derive from the medial ganglionic eminence of the embryonic subpallium and express the transcription factor Nkx2-1. These neurons fire at high rates during alert rest, and encode movements through heterogeneous firing rate changes, with many neurons decreasing their activity. In contrast, arkypallidal GPe neurons originate from lateral/caudal ganglionic eminences, express the transcription factor FoxP2, fire at low rates during rest, and encode movements with robust increases in firing. We conclude that developmental diversity positions prototypic and arkypallidal neurons to fulfil distinct roles in behavior via their disparate regulation of GABA release onto different basal ganglia targets.

Highlights

Neuronal cell type is programmed during brain development according to a tailored, combinatorial transcription factor code, with some code elements being required to maintain the identities of postmitotic neurons throughout life (Deneris and Hobert, 2014)
Focusing on the mouse external globus pallidus (GPe), we demonstrate that the potential contributions of two GABAergic GPe cell types to voluntary action are fated from early life to be distinct
Prototypic GPe neurons derive from the medial ganglionic eminence of the embryonic subpallium and express the transcription factor Nkx2-1

Summary

Introduction

Neuronal cell type is programmed during brain development according to a tailored, combinatorial transcription factor code, with some code elements being required to maintain the identities of postmitotic neurons throughout life (Deneris and Hobert, 2014). The exploitation of transcriptional codes to resolve the contributions of different cell types to behavior holds particular promise in non-laminated brain structures comprising different projection cell types that intermingle and share the same neurotransmitter phenotype, as is the case with the external globus pallidus (GPe). Despite the great utility of such conceptual schemes, the GPe is more realistically viewed as being comprised of different populations of GABAergic neuron (Kita, 2007). This is especially evident in the Parkinsonian GPe wherein two major GABAergic cell types, ‘‘prototypic’’ and ‘‘arkypallidal’’ neurons, exhibit distinct firing under anesthesia (Mallet et al, 2012). Diverse ontogeny has yet to be framed in the context of functionally defined cell types in the adult, dopamine-intact GPe

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