Modulation of synaptic transmission from primary afferents to spinal substantia gelatinosa neurons by group III mGluRs in GAD65-EGFP transgenic mice

2011 ◽  
Vol 105 (3) ◽  
pp. 1102-1111 ◽  
Author(s):  
Lian Cui ◽  
Yoo Rim Kim ◽  
Hye Young Kim ◽  
Seok Chan Lee ◽  
Hee-Sup Shin ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Action Potential ◽  
Synaptic Transmission ◽  
Dorsal Horn ◽  
Firing Pattern ◽  
Primary Afferents ◽  
Substantia Gelatinosa ◽  
Primary Afferent ◽  
Group Iii ◽  
Physiological Properties

Group III metabotropic glutamate receptors (mGluRs) are involved in nociceptive transmission in the spinal cord. However, the cellular mechanism underlying the modulation of synaptic transmission from nociceptive primary afferents to dorsal horn neurons by group III mGluRs has yet to be explored. In this study, we used transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the glutamate decarboxylase (GAD) 65 promoter to identify specific subpopulations of GABAergic inhibitory interneurons. By GABA immunolabeling, we confirmed the majority of GAD65-EGFP-expressing neurons were GABAergic. Because GAD65-EGFP-expressing neurons have not been examined in detail before, we first investigated the physiological properties of GAD65-EGFP- and non-EGFP-expressing neurons in substantia gelatinosa (SG) of the spinal dorsal horn. Membrane properties, such as the resting membrane potential, membrane capacitance, action potential threshold, and action potential height, differed significantly between these two groups of neurons. Most EGFP-expressing neurons displayed a tonic firing pattern (73% of recorded neurons) and received monosynaptic Aδ and/or C primary afferent inputs (85% of recorded neurons). In contrast, we observed a delayed firing pattern in 53% of non-EGFP-expressing neurons. After identifying the physiological properties of EGFP-expressing neurons, we tested the effects of group III mGluRs on synaptic transmission pharmacologically. A group III mGluR agonist, L-AP4, attenuated Aδ fiber-evoked synaptic transmission but did not affect C fiber-evoked synaptic transmission to EGFP-expressing neurons. Similar primary afferent-specific inhibition by L-AP4 was also observed in non-EGFP-expressing neurons. Moreover, Aδ fiber-evoked synaptic transmission was suppressed by a selective mGluR7 agonist, AMN082. These results suggest that modulation of the synaptic transmission from primary afferents to SG neurons by group III mGluR agonist is specific to the type of nociceptive primary afferents but not to the type of target neurons.

The excitability of dorsal horn neurons is affected by cerebrospinal fluid from humans with osteoarthritis

2012 ◽  
Vol 90 (6) ◽  
pp. 783-790
Author(s):  
Van B. Lu ◽  
Peter A. Smith ◽  
Saifee Rashiq
Keyword(s):  
Synaptic Transmission ◽  
Dorsal Horn ◽  
Sensory Processing ◽  
Human Subjects ◽  
Substantia Gelatinosa ◽  
Inhibitory Neurons ◽  
Membrane Properties ◽  
Electrophysiological Properties ◽  
Osteoarthritis Pain ◽  
Cultured Slices

Changes in central neural processing are thought to contribute to the development of chronic osteoarthritis pain. This may be reflected as the presence of inflammatory mediators in the cerebral spinal fluid (CSF). We therefore exposed organotypically cultured slices of rat spinal cord to CSF from human subjects with osteoarthritis (OACSF) at a ratio of 1 part CSF in 9 parts culture medium for 5–6 days, and measured changes in neuronal electrophysiological properties by means of whole-cell recording. Although OACSF had no effect on the membrane properties and excitability of neurons in the substantia gelatinosa, synaptic transmission was clearly altered. The frequency of spontaneous excitatory postsynaptic currents (sEPSC) in delay-firing putative excitatory neurons was increased, as was sEPSC amplitude and frequency in tonic-firing inhibitory neurons. These changes could affect sensory processing in the dorsal horn, and may affect the transfer of nociceptive information. Although OACSF also affected inhibitory synaptic transmission (frequency of spontaneous inhibitory synaptic currents; sIPSC), this may have little bearing on sensory processing by substantia gelatinosa neurons, as sEPSC frequency is >3× greater than sIPSC frequency in this predominantly excitatory network. These results support the clinical notion that changes in nociceptive processing at the spinal level contribute to the generation of chronic osteoarthritis pain.

scholarly journals Prior perineural or neonatal treatment with capsaicin does not alter the development of spinal microgliosis induced by peripheral nerve injury

2020 ◽  
Author(s):  
Ivett Dorina Szeredi ◽  
Gábor Jancsó ◽  
Orsolya Oszlács ◽  
Péter Sántha
Keyword(s):  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Spinal Dorsal Horn ◽  
Primary Afferents ◽  
Primary Afferent ◽  
Spinal Dorsal ◽  
C Fiber ◽  
Spinal Afferents

Abstract Peripheral nerve injury is associated with spinal microgliosis which plays a pivotal role in the development of neuropathic pain behavior. Several agents of primary afferent origin causing the microglial reaction have been identified, but the type(s) of primary afferents that release these mediators are still unclear. In this study, specific labeling of C-fiber spinal afferents by lectin histochemistry and selective chemodenervation by capsaicin were applied to identify the type(s) of primary afferents involved in the microglial response. Comparative quantitative morphometric evaluation of the microglial reaction in central projection territories of intact and injured peripheral nerves in the superficial (laminae I and II) and deep (laminae III and IV) spinal dorsal horn revealed a significant, about three-fold increase in microglial density after transection of the sciatic or the saphenous nerve. Prior perineural treatment of these nerves with capsaicin, resulting in a selective defunctionalization of C-fiber afferent fibers failed to affect spinal microgliosis. Similarly, peripheral nerve injury-induced increase in microglial density was unaffected in rats treated neonatally with capsaicin known to result in a near-total loss of C-fiber dorsal root fibers. Perineural treatment with capsaicin per se did not evoke a significant increase in microglial density. These observations indicate that injury-induced spinal microgliosis may be attributed to phenotypic changes in injured myelinated primary afferent neurons, whereas the contribution of C-fiber primary sensory neurons to this neuroimmune response is negligible. Spinal myelinated primary afferents may play a hitherto unrecognized role in regulation of neuroimmune and perisynaptic microenvironments of the spinal dorsal horn.

Adenosine inhibition of synaptic transmission in the substantia gelatinosa

1994 ◽  
Vol 72 (4) ◽  
pp. 1611-1621 ◽  
Author(s):  
J. Li ◽  
E. R. Perl
Keyword(s):  
Synaptic Transmission ◽  
Dorsal Root ◽  
Potassium Conductance ◽  
Outward Current ◽  
Postsynaptic Membrane ◽  
Substantia Gelatinosa ◽  
Equilibrium Potential ◽  
Primary Afferent ◽  
Primary Afferent Fibers ◽  
Sustained Outward Current

1. We studied adenosine's action on synaptic transmission from primary afferent fibers to neurons of the substantia gelatinosa (SG) using tight-seal whole cell recordings in transverse slices of hamster spinal cord. Adenosine had two actions, hyperpolarization of the postsynaptic membrane and depression of the excitatory postsynaptic currents (EPSCs) evoked by dorsal root stimulation. 2. Under voltage clamp adenosine elicited a sustained outward current at a holding potential of -70 mV. The outward current was blocked by a combination of intracellular cesium and tetraethylammonium, an effect characteristic of potassium channels. The adenosine-induced current reversed at -97 +/- 6 (SD) mV, close to the potassium equilibrium potential. These observations suggest that adenosine activates a potassium conductance in SG neurons so as to inhibit primary afferent synaptic transmission postsynaptically. 3. Adenosine reduced the miniature EPSC frequency without significantly changing the amplitude. In contrast, the glutamate receptor competitive antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) substantially reduced the amplitudes of miniature EPSCs while producing a much smaller effect on the miniature frequency than adenosine. In evoked EPSCs adenosine reduced unitary content without reducing unitary amplitude. The effects on both miniature and evoked EPSCs suggest that adenosine inhibits synaptic currents by suppressing presynaptic transmitter release. 4. EPSCs evoked by dorsal root stimuli were subdivided into monosynaptic and polysynaptic categories. Adenosine at superfusion concentrations of 20-300 microM suppressed all polysynaptic EPSCs. Less than half of monosynaptic EPSCs were inhibited, usually those evoked by the slowest-conducting primary afferents. These observations were interpreted to indicate that a principal action of adenosine in SG is on interneuronal communication.

Sciatic Chronic Constriction Injury Produces Cell-Type-Specific Changes in the Electrophysiological Properties of Rat Substantia Gelatinosa Neurons

2006 ◽  
Vol 96 (2) ◽  
pp. 579-590 ◽  
Author(s):  
Sridhar Balasubramanyan ◽  
Patrick L. Stemkowski ◽  
Martin J. Stebbing ◽  
Peter A. Smith
Keyword(s):  
Action Potential ◽  
Dorsal Horn ◽  
Chronic Constriction Injury ◽  
Input Resistance ◽  
Substantia Gelatinosa ◽  
Resting Membrane Potential ◽  
Cellular Mechanisms ◽  
Electrophysiological Properties ◽  
Putative Role ◽  
Cell Recording

Peripheral nerve injury increases spontaneous action potential discharge in spinal dorsal horn neurons and augments their response to peripheral stimulation. This “central hypersensitivity, ” which relates to the onset and persistence of neuropathic pain, reflects spontaneous activity in primary afferent fibers as well as long-term changes in the intrinsic properties of the dorsal horn (centralization). To isolate and investigate cellular mechanisms underlying “centralization,” sciatic nerves of 20-day-old rats were subjected to 13–25 days of chronic constriction injury (CCI; Mosconi-Kruger polyethylene cuff model). Spinal cord slices were then acutely prepared from sham-operated or CCI animals, and whole cell recording was used to compare the properties of five types of substantia gelatinosa neuron. These were defined as tonic, irregular, phasic, transient, or delay according to their discharge pattern in response to depolarizing current. CCI did not affect resting membrane potential, rheobase, or input resistance in any neuron type but increased the amplitude and frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) in delay, transient, and irregular cells. These changes involved alterations in the action potential-independent neurotransmitter release machinery and possible increases in the postsynaptic effectiveness of glutamate. By contrast, in tonic cells, CCI reduced the amplitude and frequency of spontaneous and miniature EPSCs. Such changes may relate to the putative role of tonic cells as inhibitory GABAergic interneurons, whereas increased synaptic drive to delay cells may relate to their putative role as the excitatory output neurons of the substantia gelatinosa. Complementary changes in synaptic excitation of inhibitory and excitatory neurons may thus contribute to pain centralization.

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