Encoding mechanisms for sensory neurons studied with a multielectrode array in the cat dorsal root ganglion

2004 ◽  
Vol 82 (8-9) ◽  
pp. 757-768 ◽  
Author(s):  
R B Stein ◽  
Y Aoyagi ◽  
D J Weber ◽  
S Shoham ◽  
R A Normann

Recent advances in microelectrode array technology now permit a direct examination of the way populations of sensory neurons encode information about a limb's position in space. To address this issue, we recorded nerve impulses from about 100 single units simultaneously in the L6 and L7 dorsal root ganglia (DRG) of the anesthetized cat. Movement sensors, placed near the hip, knee, ankle, and foot, recorded passive movements of the cat's limb while it was moved pseudo-randomly. The firing rate of the neurons was correlated with the position of the limb in various coordinate systems. The firing rates were less correlated to the position of the foot in Cartesian coordinates (x, y) than in joint angular coordinates (hip, knee, ankle), or in polar coordinates. A model was developed in which position and its derivatives are encoded linearly, followed by a nonlinear spike-generating process. Adding the nonlinear portion significantly increased the correlations in all coordinate systems, and the full models were able to accurately predict the firing rates of various types of sensory neurons. The observed residual variability is captured by a simple stochastic model. Our results suggest that compact encoding models for primary afferents recorded at the DRG are well represented in polar coordinates, as has previously been suggested for the cortical and spinal representation of movement. This study illustrates how sensory receptors encode a sense of limb position, and it provides a general framework for modeling sensory encoding by populations of neurons.Key words: sensory, encoding, multielectrode, dorsal root ganglion, cutaneous, muscle.

Author(s):  
Edward C. Emery ◽  
Patrik Ernfors

Primary sensory neurons of the dorsal root ganglion (DRG) respond and relay sensations that are felt, such as those for touch, pain, temperature, itch, and more. The ability to discriminate between the various types of stimuli is reflected by the existence of specialized DRG neurons tuned to respond to specific stimuli. Because of this, a comprehensive classification of DRG neurons is critical for determining exactly how somatosensation works and for providing insights into cell types involved during chronic pain. This article reviews the recent advances in unbiased classification of molecular types of DRG neurons in the perspective of known functions as well as predicted functions based on gene expression profiles. The data show that sensory neurons are organized in a basal structure of three cold-sensitive neuron types, five mechano-heat sensitive nociceptor types, four A-Low threshold mechanoreceptor types, five itch-mechano-heat–sensitive nociceptor types and a single C–low-threshold mechanoreceptor type with a strong relation between molecular neuron types and functional types. As a general feature, each neuron type displays a unique and predicable response profile; at the same time, most neuron types convey multiple modalities and intensities. Therefore, sensation is likely determined by the summation of ensembles of active primary afferent types. The new classification scheme will be instructive in determining the exact cellular and molecular mechanisms underlying somatosensation, facilitating the development of rational strategies to identify causes for chronic pain.


Author(s):  
Kentaro Nishida ◽  
Yuka Nomura ◽  
Kanako Kawamori ◽  
Akihiro Ohishi ◽  
Kazuki Nagasawa

In dorsal root ganglion (DRG) neurons, ATP is an important neurotransmitter in nociceptive signaling through P2 receptors (P2Rs) such as P2X2/3R, and adenosine is also involved in anti-nociceptive signaling through adenosine A1R. Thus, the clearance system for adenine nucleotide/nucleoside plays a critical role in regulation of nociceptive signaling, but there is little information on it, especially ectoenzyme expression profiles in DRG. In this study, we examined expression and localization of ecto-nucleotide pyrophosphatase/phosphodiesterases (ENPPs), by which ATP is metabolized to AMP, in rat DRG. The mRNA expression levels of ENPP2 were greater than those of ENPP1 and ENPP3 in rat DRGs. On immunohistochemical analysis, ENPP1, 2 and 3 were found in soma of DRG neurons. Immunopositive rate of ENPP3 was greater than that of ENPP1 and ENPP2 in all DRG neurons. ENPP3, as compared with ENPP1 and ENPP2, was expressed mainly by isolectin B4-positive cells, and slightly by neurofilament 200-positive ones. In this way, the expression profile of ENPP1, 2 and 3 was different in DRGs, and they were mainly expressed in small/medium-sized DRG neurons. Moreover, ENPP1-, 2- and 3-immunoreactivities were colocalized with P2X2R, P2X3R and prostatic acid phosphatase (PAP), as an ectoenzyme for metabolism from AMP to adenosine. Additionally, PAP-immunoreactivity was colocalized with equilibrative nucleoside transporter (ENT) 1, as an adenosine uptake system. These results suggest that the clearance system consisted of ENPPs, PAP and ENT1 plays an important role in regulation of nociceptive signaling in sensory neurons.


2014 ◽  
Vol 5;17 (5;9) ◽  
pp. E609-E618
Author(s):  
Nebojsa N. Knezevic

Background: Epidural and intrathecal injections of methylprednisolone acetate (MPA) have become the most commonly performed interventional procedures in the United States and worldwide in the last 2 decades. However neuraxial MPA injection has been dogged by controversy regarding the presence of different additives used in commercially prepared glucocorticoids. We previously showed that MPA could be rendered 85% free of polyethylene glycol (PEG) by a simple physical separation of elements in the suspension. Objective: The objective of the present study was to explore a possible cytotoxic effect of commercially available MPA (with intact or reduced preservatives) on rat sensory neurons. Methods: We exposed primary dissociated rat dorsal root ganglia (DRG) sensory neurons to commercially available MPA for 24 hours with either the standard (commercial) concentration of preservatives or to different fractions following separation (MPA suspension whose preservative concentration had been reduced, or fractions containing higher concentrations of preservatives). Cells were stained with the TUNEL assay kit to detect apoptotic cells and images were taken on the Bio-Rad Laser Sharp-2000 system. We also detected expression of caspase-3, as an indicator of apoptosis in cell lysates. Results: We exposed sensory neurons from rat DRG to different concentrations of MPA from the original commercially prepared vial. TUNEL assay showed dose-related responses and increased percentages of apoptotic cells with increasing concentrations of MPA. Increased concentrations of MPA caused 1.5 – 2 times higher caspase-3 expression in DRG sensory neurons than in control cells (ANOVA, P = 0.001). Our results showed that MPA with reduced preservatives caused significantly less apoptosis observed with TUNEL assay labeling (P < 0.001) and caspase-3 immunoblotting (P ≤ 0.001) than in neurons exposed to MPA from a commercially prepared vial or “clear phase” that contained higher concentrations of preservatives. Even though MPA with reduced preservatives caused 12.5% more apoptosis in DRG sensory neurons than in control cells, post hoc analysis showed no differences between these 2 groups. Limitations: Our data was collected from in vitro isolated rat DRG neurons. There is a possibility that in vivo neurons have different extents of vulnerability compared to isolated neurons. Conclusions: Results of the present study identified a cytotoxic effect of commercially available MPA with preservatives or with a “clear phase” containing higher concentrations of preservatives on primary isolated rat DRG sensory neurons. This was shown by TUNEL positive assay and by increased caspase-3 expression as one of the final executing steps in apoptotic pathways in DRG neurons. However, our results showed no statistically significant difference between the control cells (salinetreated) and cells treated with MPA with reduced concentrations of preservatives, pointing out that either PEG or myristylgamma-picolinium chloride (MGPC) or their combination have harmful effects on these cells. Reduction of concentrations of preservatives from commercially available MPA suspensions by using the simple method of inverting vials for 2 hours could be considered useful in clinical practice to enhance the safety of this depot steroid when injected neuraxially. Key words: Methylprednisolone acetate, preservatives, dorsal root ganglion sensory neurons, cytotoxic effect, polyethylene glycol, myristylgamma-picolinium chloride


2015 ◽  
Vol 39 (2) ◽  
pp. 42-46
Author(s):  
Ali Ghanim Al-Okaili

     The aim of the study is to compare the histological changes that occur in the sensory neurons of dorsal root ganglion at L6 and L7 levels of the spinal nerve in different age groups in rabbits. Fifteen rabbits were divided into three groups of equal number according to their age (weaning, maturation and adult). Dorsal root ganglion of spinal nerve at L6 and L7 levels were removed and examined histologically under light microscope. Comparison were made in diameters of neurons and their numbers in different age. The results showed a significant (P<0.05) decrease in the number of sensory neurons and a significant (P<0.05) increase in their diameters with advancing age. In conclusion, the structures of sensory neurons are altering by the age factors in which morphology, number, and color of neurons change also.


Development ◽  
2002 ◽  
Vol 129 (11) ◽  
pp. 2639-2648 ◽  
Author(s):  
Robert A. Cornell ◽  
Judith S. Eisen

In zebrafish, cells at the lateral edge of the neural plate become Rohon-Beard primary sensory neurons or neural crest. Delta/Notch signaling is required for neural crest formation. ngn1 is expressed in primary neurons; inhibiting Ngn1 activity prevents Rohon-Beard cell formation but not formation of other primary neurons. Reducing Ngn1 activity in embryos lacking Delta/Notch signaling restores neural crest formation, indicating Delta/Notch signaling inhibits neurogenesis without actively promoting neural crest. Ngn1 activity is also required for later development of dorsal root ganglion sensory neurons; however, Rohon-Beard neurons and dorsal root ganglion neurons are not necessarily derived from the same precursor cell. We propose that temporally distinct episodes of Ngn1 activity in the same precursor population specify these two different types of sensory neurons.


1993 ◽  
Vol 13 (11) ◽  
pp. 4880-4888 ◽  
Author(s):  
KJ Tomaselli ◽  
P Doherty ◽  
CJ Emmett ◽  
CH Damsky ◽  
FS Walsh ◽  
...  

1995 ◽  
Vol 73 (5) ◽  
pp. 1793-1798 ◽  
Author(s):  
M. D. Womack ◽  
E. W. McCleskey

1. Using patch-clamp methods, we show that brief prepulses to very positive voltages increase (facilitate) the amplitude of current through Ca2+ channels during a subsequent test pulse in some, but not all, dorsal root ganglion (DRG) sensory neurons. The amplitude of this facilitated current generally increases when the Ca2+ channels are inhibited by activation of the mu-opioid receptor. 2. The facilitated current is blocked by omega-conotoxin GVIA, activates in the range of high-threshold Ca2+ channels, and inactivates at relatively negative holding voltages. Thus facilitated current passes through N-type Ca2+ channels, the same channels that are inhibited by opioids and control neurotransmitter release in sensory neurons. 3. Although maximal facilitation occurs only at unphysiologically high membrane potentials (above +100 mV), some facilitation is seen after prepulses to voltages reached during action potentials. After return to the holding potential, facilitation persists for hundreds of milliseconds, considerably longer than in other neurons. Brief trains of pulses designed to mimic action potentials caused small facilitation (19% of maximal) in a fraction (8 of 24) of opioid-inhibited neurons. 4. We conclude that 1) prepulses to extremely positive voltages can cause partial recovery of Ca2+ channels inhibited by opioids; and 2) small, but detectable, facilitation is also seen after physiological stimulation in some DRG neurons. Facilitation, largely considered a biophysical epiphenomenon because of the extreme voltages used to induce it, appears to be physiologically relevant during opioid inhibition of Ca2+ channels in DRG neurons.


2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Javier Sábado ◽  
Anna Casanovas ◽  
Olga Tarabal ◽  
Marta Hereu ◽  
Lídia Piedrafita ◽  
...  

Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs). Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations ofsuperoxide dismutase 1(SOD1) gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used theSOD1G93Amouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG) proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.


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