scholarly journals Evidence for genetically distinct direct and indirect spinocerebellar pathways mediating proprioception

2020 ◽  
Author(s):  
Iliodora V. Pop ◽  
Felipe Espinosa ◽  
Megan Goyal ◽  
Bishakha Mona ◽  
Mark A. Landy ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Cerebellar Nuclei ◽  
Reticular Nucleus ◽  
Proprioceptive Information ◽  
Lateral Reticular Nucleus ◽  
Axon Collaterals ◽  
Progenitor Domain ◽  
Clarke's Column

AbstractProprioception, the sense of limb and body position, generates a map of the body that is essential for proper motor control, yet we know little about precisely how neurons in proprioceptive pathways develop and are wired. Proprioceptive and cutaneous information from the periphery is sent to secondary neurons in the spinal cord that integrate and relay this information to the cerebellum either directly or indirectly through the medulla. Defining the anatomy of these direct and indirect pathways is fundamental to understanding how proprioceptive circuits function. Here, we use genetic tools in mice to define the developmental origins and unique anatomical trajectories of these pathways. Developmentally, we find that Clarke’s column (CC) neurons, a major contributor to the direct spinocerebellar pathway, derive from the Neurog1 progenitor domain. By contrast, we find that two of the indirect pathways, the spino-lateral reticular nucleus (spino-LRt) and spino-olivary pathways, are derived from the Atoh1 progenitor domain, despite previous evidence that Atoh1-lineage neurons form the direct pathway. Anatomically, we also find that the mossy fiber terminals of CC neurons diversify extensively with some axons terminating bilaterally in the cerebellar cortex. Intriguingly, we find that CC axons do not send axon collaterals to the medulla or cerebellar nuclei like other mossy fiber sources. Altogether, we conclude that the direct and indirect spinocerebellar pathways derive from distinct progenitor domains in the developing spinal cord and that the proprioceptive information from CC neurons is processed only at the level of granule cells in the cerebellum.Significance StatementWe find that a majority of direct spinocerebellar neurons in mice originate from Clarke’s column (CC), which derives from the Neurog1-lineage, while few originate from Atoh1-lineage neurons as previously thought. Instead, we find that spinal cord Atoh1-lineage neurons form mainly the indirect spino-lateral reticular nucleus and spino-olivary tracts. Moreover, we observe that mossy fiber axon terminals of CC neurons diversify proprioceptive information across granule cells in multiple lobules on both ipsilateral and contralateral sides without sending axon collaterals to the medulla or cerebellar nuclei. Altogether, we define the development and the anatomical projections of direct and indirect pathways to the cerebellum from the spinal cord.

scholarly journals The relationship between birth timing, circuit wiring, and physiological response properties of cerebellar granule cells

2021 ◽  
Vol 118 (23) ◽  
pp. e2101826118
Author(s):  
S. Andrew Shuster ◽  
Mark J. Wagner ◽  
Nathan Pan-Doh ◽  
Jing Ren ◽  
Sophie M. Grutzner ◽  
...  
Keyword(s):  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Mossy Fiber ◽  
Molecular Layer ◽  
Cerebellar Nuclei ◽  
Birth Timing ◽  
Imaging Data ◽  
Cerebellar Granule ◽  
Virus Tracing

Cerebellar granule cells (GrCs) are usually regarded as a uniform cell type that collectively expands the coding space of the cerebellum by integrating diverse combinations of mossy fiber inputs. Accordingly, stable molecularly or physiologically defined GrC subtypes within a single cerebellar region have not been reported. The only known cellular property that distinguishes otherwise homogeneous GrCs is the correspondence between GrC birth timing and the depth of the molecular layer to which their axons project. To determine the role birth timing plays in GrC wiring and function, we developed genetic strategies to access early- and late-born GrCs. We initiated retrograde monosynaptic rabies virus tracing from control (birth timing unrestricted), early-born, and late-born GrCs, revealing the different patterns of mossy fiber input to GrCs in vermis lobule 6 and simplex, as well as to early- and late-born GrCs of vermis lobule 6: sensory and motor nuclei provide more input to early-born GrCs, while basal pontine and cerebellar nuclei provide more input to late-born GrCs. In vivo multidepth two-photon Ca2+ imaging of axons of early- and late-born GrCs revealed representations of diverse task variables and stimuli by both populations, with modest differences in the proportions encoding movement, reward anticipation, and reward consumption. Our results suggest neither organized parallel processing nor completely random organization of mossy fiber→GrC circuitry but instead a moderate influence of birth timing on GrC wiring and encoding. Our imaging data also provide evidence that GrCs can represent generalized responses to aversive stimuli, in addition to recently described reward representations.

Electrophysiological characteristics of lumbar spinal cord neurons backfired from lateral reticular nucleus in the rat

1984 ◽  
Vol 52 (4) ◽  
pp. 595-611 ◽  
Author(s):  
D. Menetrey ◽  
J. de Pommery ◽  
J. M. Besson
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Receptive Fields ◽  
Reticular Nucleus ◽  
Lumbar Spinal Cord ◽  
High Threshold ◽  
Lateral Reticular Nucleus ◽  
Spinal Cord Neurons ◽  
Electrophysiological Properties ◽  
Lumbar Spinal

Spinal neurons antidromically activated from either the lateral reticular nucleus (LRN) or immediately adjacent areas were identified in the rat lumbar spinal cord. In agreement with previous anatomical work (60), these neurons were widely distributed in both the dorsal and ventral horns of the spinal cord and could be subdivided into three main groups according to their location: a) deep ventromedial (DVM) cells, which project more substantially to the LRN than to other supraspinal targets; b) cells of the median portion of the neck of the dorsal horn (mNDH), which project exclusively to the LRN; c) cells lying in other parts of the dorsal horn (superficial layers, nucleus proprius, reticular extension of the neck), by their location, they are indistinguishable from cells projecting to other supraspinal targets. The probability is high that the DVM and mNDH cells contribute exclusively, or at least preferentially, to the lateral component of the spinoreticular tract (lSRT), defined as the direct spinal pathway to the LRN. Although electrophysiological properties of cells were clearly related to their spinal location, several subpopulations could be recognized in each of the three main groups. The majority of DVM neurons were in lamina VII, with some in laminae VI, VIII, and X. With the exception of a few lamina X cells, the DVM neurons had high conduction velocities. Four subpopulations of these neurons were recognized. a) Innocuous proprioceptive cells responded to small changes in joint position, some showing convergence of nonnoxious cutaneous inputs. b) High-threshold cells (approximately 50% of DVM cells). Seventy-five percent of these cells were excited from bilateral receptive fields (mostly symmetric) with noxious cutaneous pinching that extended to subcutaneous tissues. Their evoked responses had long-lasting postdischarges that continued up to several minutes after cessation of the stimulus. c) Inhibited cells had no demonstrable excitatory receptive fields and a high ongoing activity that was tonically depressed by pressure or pinch; poststimulus effects of long duration were observed. d) Cells with no resting discharge and demonstrable excitatory peripheral receptive fields. mNDH cells had recording sites at the medial border of the internal portion of the reticular area of the neck of the dorsal horn.(ABSTRACT TRUNCATED AT 400 WORDS)

Reticulospinal neurons with and without monosynaptic inputs from cerebellar nuclei

1975 ◽  
Vol 38 (3) ◽  
pp. 513-530 ◽  
Author(s):  
J. C. Eccles ◽  
R. A. Nicoll ◽  
W. F. Schwarz ◽  
H. Taborikova ◽  
T. J. Willey
Keyword(s):  
Spinal Cord ◽  
Receptive Fields ◽  
Cerebellar Nuclei ◽  
Reticular Nucleus ◽  
Antidromic Activation ◽  
Reticulospinal Neurons ◽  
Mean Values ◽  
Air Jet ◽  
Reticular Neurons ◽  
Stimulation Of

An account is given of the responses of 557 medial reticular neurons with axons projecting down the spinal cord. All 30 experiments were on decerebrated unanesthetized cats paralyzed by Flaxedil. Recording from single neurons was by extracellular glass microelectrodes. Identification was first by location (confirmed by subsequent histology) in the medial reticular nucleus of medulla or pons, and second by antidromic activation from cord stimulation at C2 and L2 segmental levels. Axonal conduction velocities were calculated from the latency differential between L2 and C2 antidromic responses, and were usually in the range of 90-140 m/s; but about 25% were slower, ranging down to 30 m/s. Stimulation by electrodes in the ipsilateral and contralateral fastigial nuclei differentiated reticulospinal neurons into two classes according to whether they did or did not receive monosynaptic inputs, the respective populations of fully investigated neurons being 270 and 174. The fastigioreticular neurons were distinguished by a higher background frequency with mean values of 28 as against 15/s. There were also significant diffences in both the excitatory and inhibitory responses to afferent volleys from forelimb and hindlimb nerves. Comparison of the respective latency histograms showed that the responses of neurons with a fastigial input had an excess of latencies in the ranges that can be correlated with the latency histograms observed for fastigial responses. Thus, there is evidence for the effectiveness of the fastigial input and so for the pathway with monosynaptic linkage: Purkinje cells of cerebellar vermis yields fastigial neurons yields medial reticular neurons projecting down the spinal cord. Adequate stimulation of cutaneous receptors by pad taps and air-jet stimulation of hairy skin in a disppointingly small action when compared with fastigical responses. Explanations of this deficiency are suggested. Another discrpancy from the fastigial responses is that the medial reticular neurons have much wider receptive fields with little discrimination between ipsilateral and contralateral and between forelimb and hindlimb. Stimulation of the ipsilateral tegmental tract was tested on 183 reticulospinal neurons, 112 being with fastigial inputs. In about half there was a powerful monosynaptic excitation, which would identify such neurons as being on the pathway from mesencephalic and diencephalic centers to the spinal cord. There is a general discussion of transmission across successive synaptic relays, where specificity is sacrificed to integration.

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