The diversity of neuronal phenotypes in rodent and human autonomic ganglia

Abstract

Selective sympathetic and parasympathetic pathways that act on target organs represent the terminal actors in the neurobiology of homeostasis and often become compromised during a range of neurodegenerative and traumatic disorders. Here, we delineate several neurotransmitter and neuromodulator phenotypes found in diverse parasympathetic and sympathetic ganglia in humans and rodent species. The comparative approach reveals evolutionarily conserved and non-conserved phenotypic marker constellations. A developmental analysis examining the acquisition of selected neurotransmitter properties has provided a detailed, but still incomplete, understanding of the origins of a set of noradrenergic and cholinergic sympathetic neuron populations, found in the cervical and trunk region. A corresponding analysis examining cholinergic and nitrergic parasympathetic neurons in the head, and a range of pelvic neuron populations, with noradrenergic, cholinergic, nitrergic, and mixed transmitter phenotypes, remains open. Of particular interest are the molecular mechanisms and nuclear processes that are responsible for the correlated expression of the various genes required to achieve the noradrenergic phenotype, the segregation of cholinergic locus gene expression, and the regulation of genes that are necessary to generate a nitrergic phenotype. Unraveling the neuron population-specific expression of adhesion molecules, which are involved in axonal outgrowth, pathway selection, and synaptic organization, will advance the study of target-selective autonomic pathway generation.

Diversity of satellite glia in sympathetic and sensory ganglia

“…In the peripheral nervous system, the sensory arm is essential for transducing a wide variety of environmental stimuli from the outside world to the central nervous system, while the sympathetic division relays motor commands from the central nervous system to diverse peripheral organs/tissues to mobilize the “fight or flight” response and maintain body homeostasis in response to a continuously changing environment (Goldstein, 2013; Marmigere and Ernfors, 2007; Usoskin et al, 2015). Sympathetic and sensory neurons residing in their respective peripheral ganglia are remarkably diverse with respect to morphological, molecular, and electrophysiological properties, consistent with their distinct functions (Ernsberger et al, 2020; Liu and Ma, 2011). In addition to primary neurons, sympathetic and sensory ganglia contain two major glial cell types, satellite glia and Schwann cells, which are closely associated with their neuronal neighbors and influence a wide range of neuronal functions (Hanani and Spray, 2020; Jessen and Mirsky, 2005).…”

The sympathies of the body: functional organization and neuronal differentiation in the peripheral sympathetic nervous system

“…The molecules responsible for wiring this network are to a large extent unknown. With the characterization of mouse thoracic sympathetic neurons by RNA sequencing (Furlan et al 2016 ), the expression of transcripts for synaptic organizer molecules in sympathetic piloerector neurons is available (Ernsberger et al 2020 ) that may be part of a neuron class-specific wiring code.

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“…For protocadherin transcripts, several important aspects could be derived from the single cell RNA sequencing data published by Furlan et al ( 2016 ). Compared to other cell adhesion and synaptic organizer molecules, the PCDH gene family members are expressed very selectively in the different classes of sympathetic neurons (Ernsberger et al 2020 ). For PCDH17, significant transcript levels are detected only in cholinergic neurons, not in noradrenergic neurons.…”

“…The growth factor-induced differentiation process is driven by a transcription factor (TF) network critically involving PHOX2b, HAND1 and HAND2, and GATA2 and GATA3, linked by cross regulatory capacity (Rohrer 2011 ; Ernsberger and Rohrer 2018 ; Ernsberger et al 2020 ). Notably, PHOX2b is required for initiation of the noradrenergic and neuronal differentiation process (Pattyn et al 1999 ) and for maintenance of noradrenergic marker expression in differentiated neurons (Coppola et al 2010 ).…”

“…In the almost 300 years since then, the progress of discoveries in the field of the autonomic nervous system, including the sympathetic nervous system, spins at an ever increasing rate. The progressing understanding of the cellular properties realized in the autonomic sympathetic and parasympathetic system (Ernsberger and Rohrer 2018 ), and in particular, in the postganglionic sympathetic neurons (Ernsberger et al 2020 ), now becomes refined to molecular detail by single cell RNA sequencing (Furlan et al 2016 ; Blum et al 2021 ). Together with the studies on the integration of these neurons in autonomic reflex pathways, a comprehension of the circuits maintaining bodily homeostasis is developing (Jänig 2006 ).…”