Biology subjects

Chopek, J. W.

Publications and source records attributed to Chopek, J. W..

3 recordsLinked to original sources

bioRxiv2025

Ascending propriospinal modulation of thoracic sympathetic preganglionic neurons during lumbar locomotor activity

Although the autonomic sympathetic system is activated in parallel with locomotion, the underlying neural mechanisms mediating this coordination are not completely understood. Descending exercise or central command signals from hypothalamic and brainstem regions are thought to activate thoracic spinal sympathetic neurons in parallel with descending locomotor commands. In turn, subsets of thoracic sympathetic preganglionic neurons (SPNs) then increase activation of a constellation of tissues and organs that provide homeostatic and metabolic support during movement and exercise. It is known that neurons within the spinal cord (propriospinal networks) can generate well-coordinated and sustained locomotor activity but whether these propriospinal networks contribute to coordination between locomotor and autonomic systems is unknown. To investigate this, we applied neurochemicals to elicit whole-cord or lumbar-evoked locomotor activity in an in vitro spinal cord preparation, simultaneously recording lumbar ventral root (VR) activity and changes in calcium fluorescence of pre-labelled SPNs in thoracic segments. Using whole-bath drug application to elicit hindlimb locomotor activity, recorded SPN responses were increased in rostral (T4 - T7) compared to caudal (T8 - T11) segments. When locomotor-inducing neurochemicals were applied only to the lumbar region using a split-bath configuration, SPN population responses were increased in rostral (T4-7) but not caudal (T8-9) segments during both tonic and rhythmic VR activity. In both approaches, the greatest numbers of SPNs with increased fluorescence during rhythmic activity were in T6/7, whereas the greatest numbers with unchanged or decreased fluorescence were in caudal segments (T8-T11). Together these findings reveal a strong ascending lumbar to thoracic integrating communication pathway and may represent a key feature of spinal neural network function normally. Such communication pathways should be further investigated for targeted autonomic function(s) activation and therapeutic benefit after spinal cord injury.

neuroscience↗

bioRxiv2023

Lumbar locomotor-related V3 interneurons provide direct excitatory synaptic input onto thoracic sympathetic preganglionic neurons

Spinal cord injury (SCI) is a life-altering event causing sensation loss, motor paralysis and impaired autonomic function. Electrical spinal cord stimulation has shown promise for restoring lost motor, and impaired autonomic function, despite targeting lumbar locomotor networks. Sympathetic preganglionic neurons (SPNs), primarily located in the intermediate laminae of thoracic and upper lumbar segments (T1-L2), provide neural input to excite sympathetic tissues and organs that provide homeostatic and metabolic support during movement and exercise. We hypothesized that ascending propriospinal neurons located in the lumbar spinal cord provide synaptic input to thoracic SPNs, providing a spinal neural mechanism explaining improved motor and autonomic function in response to spinal cord stimulation. Here, we demonstrate that synaptic contacts from locomotor-related V3 interneurons (INs) are present in all thoracic laminae. Injection of an anterograde tracer into lumbar segments demonstrated that 8-20% of glutamatergic input onto SPNs originated from lumbar V3 INs and displayed a somatotopographical organization of synaptic input to thoracic SPNs, with rostral lumbar V3 INs projecting to rostral thoracic, and caudal lumbar V3 INs projecting to caudal thoracic SPNs. Whole cell patch clamp recording in SPNs demonstrated prolonged depolarizations or action potentials in response to optical activation of either lumbar V3 INs in spinal cord preparations or in response to optical activation of V3 terminals in thoracic slice preparations. This work demonstrates a direct intraspinal connection between lumbar locomotor and thoracic sympathetic networks and suggests communication between motor and autonomic systems may be a general function of the spinal cord. Key pointsO_LIWe provide direct anatomical and electrophysiological evidence of an ascending intraspinal synaptic connection between lumbar motor and thoracic sympathetic autonomic neural systems. C_LIO_LIThese connections are formed between lumbar locomotor related V3 interneurons and thoracic sympathetic preganglionic neurons (SPNs) C_LIO_LIV3 synaptic input accounts for [~] 20% of glutamatergic input to SPNs. C_LIO_LIOptical activation of lumbar V3 interneurons elicit action potentials in thoracic SPNs. C_LIO_LIThis intraspinal pathway may explain why electrical stimulation of the lumbar region in persons with long-standing motor complete spinal cord injury improves both motor and sympathetic function. C_LIO_LIThese findings suggest communication between motor and autonomic systems may be a general feature of spinal cord function and await further research to explore this concept. C_LI

neuroscience↗

bioRxiv2021

Local brainstem circuits contribute to reticulospinal output in the mouse

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. 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 sub-populations of Chx10-expressing neurons in this region, based on distinct electrophysiological properties and somata size (small and large), and show that these 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 interneurons project to and facilitate the firing of Chx10 reticulospinal neurons. We discuss the implications of these microcircuits in terms of movement selection. SIGNIFICANCE STATEMENTReticulospinal neurons in the medullary reticular formation play a key role in movement. The transcriptional regulator Chx10 defines a population of glutamatergic neurons in this region, a proportion of which have been shown to be involved in stopping, steering, and modulating locomotion. While it has been shown that these neurons integrate descending inputs, we asked whether local processing also ultimately contributes to reticulospinal outputs. Here, we define Chx10-expressing medullary reticular formation interneurons and reticulospinal neurons, and demonstrate how the former modulate the output of the latter. The results shed light on the internal organization and microcircuit formation of reticular formation neurons.

neuroscience↗