Intrinsic brainstem circuits comprised of Chx10-expressing neurons contribute to reticulospinal output in mice.

Jeremy W Chopek,Ying Zhang,Robert M Brownstone

doi:10.1152/jn.00322.2021

Abstract

Glutamatergic reticulospinal neurons in the gigantocellular reticular nucleus (GRN) of the medullary reticular formation can function as command neurons, transmitting motor commands to spinal cord circuits to instruct movement. Recent advances in our understanding of this neuron-dense region have been facilitated by the discovery of expression of the transcriptional regulator, Chx10, in excitatory reticulospinal neurons. Here, we address the capacity of local circuitry in the GRN to contribute to reticulospinal output. We define two subpopulations of Chx10-expressing neurons in this region, based on distinct electrophysiological properties and soma size (small and large), and show that these populations correspond to local interneurons and reticulospinal neurons, respectively. Using focal release of caged glutamate combined with patch clamp recordings, we demonstrated that Chx10 neurons form microcircuits in which the Chx10 local interneurons project to and facilitate the firing of Chx10 reticulospinal neurons. We discuss the implications of these microcircuits in terms of movement selection.NEW & NOTEWORTHY Reticulospinal neurons in the medullary reticular formation integrate inputs from higher regions to effectively instruct spinal motor circuits. Using photoactivation of neurons in brainstem slices, we studied connectivity of reticular formation neurons that express the transcriptional regulator, Chx10. We show that a subpopulation of these neurons functions as local interneurons that affect descending commands. The results shed light on the internal organization and microcircuit formation of reticular formation neurons.

Highlights

As intrinsic neuronal electrophysiological properties play a critical role in producing circuit activity [33], we first sought to characterize these properties of medial medullary reticular formation Chx10 neurons, focusing on those in the rostral gigantocellular reticular nucleus (GRN)
To understand how the medullary reticular formation (medRF) contributes to movement, it is important to understand whether this region serves mainly to integrate supramedullary motor commands for transmission to the spinal cord, or whether there is local circuit processing
We demonstrated that there are at least two anatomically, physiologically, and functionally distinctive subtypes of Chx10 neurons in the rostral GRN, one with large somata that is reticulospinal, and the other with smaller somata that comprised of locally projecting excitatory interneurons

Summary

Introduction

The cortex and basal ganglia are involved in making these selections [1, 2], it is the brainstem reticular formation that must decode these supramedullary inputs to form precise commands that descend, via reticulospinal pathways, to spinal motor circuits [3]. Neurons in supramedullary locomotor regions such as the mesencephalic (MLR) and cerebellar locomotor regions project to the GRN, where they are integrated to initiate locomotion via reticulospinal pathways that in turn activate spinal locomotor circuits [7, 8]. Glutamatergic RSNs are involved in other movements as well: for example, these neurons receive input from postural centers to ensure appropriate extensor tone during motor activities (for review, see Ref. 11)

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