scholarly journals Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn

2019 ◽  
Author(s):  
Kwan Yeop Lee ◽  
Stéphanie Ratté ◽  
Steven A. Prescott
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Receptive Fields ◽  
Cell Types ◽  
Excitatory Input ◽  
Inhibitory Neurons ◽  
Somatosensory Processing ◽  
Spinal Dorsal ◽  
Excitatory Neurons ◽  
Strong Excitation

ABSTRACTNeuropathic pain is a debilitating condition caused by the abnormal processing of somatosensory input. Synaptic inhibition in the spinal dorsal horn plays a key role in that processing. Mechanical allodynia – the misperception of light touch as painful – occurs when inhibition is compromised. Disinhibition is due primarily to chloride dysregulation caused by hypofunction of the potassium-chloride co-transporter KCC2. Here we show, in rats, that excitatory neurons are disproportionately affected. This is not because chloride is differentially dysregulated in excitatory and inhibitory neurons, but, rather, because excitatory neurons rely more heavily on inhibition to counterbalance strong excitation. Receptive fields in both cell types have a center-surround organization but disinhibition unmasks more excitatory input to excitatory neurons. Differences in intrinsic excitability also affect how chloride dysregulation affects spiking. These results deepen understanding of how excitation and inhibition are normally balanced in the spinal dorsal horn, and how their imbalance disrupts somatosensory processing.

scholarly journals Excitatory neurons are more disinhibited than inhibitory neurons by chloride dysregulation in the spinal dorsal horn

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kwan Yeop Lee ◽  
Stéphanie Ratté ◽  
Steven A Prescott
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Receptive Fields ◽  
Cell Types ◽  
Excitatory Input ◽  
Inhibitory Neurons ◽  
Somatosensory Processing ◽  
Spinal Dorsal ◽  
Excitatory Neurons ◽  
Strong Excitation

Neuropathic pain is a debilitating condition caused by the abnormal processing of somatosensory input. Synaptic inhibition in the spinal dorsal horn plays a key role in that processing. Mechanical allodynia – the misperception of light touch as painful – occurs when inhibition is compromised. Disinhibition is due primarily to chloride dysregulation caused by hypofunction of the potassium-chloride co-transporter KCC2. Here we show, in rats, that excitatory neurons are disproportionately affected. This is not because chloride is differentially dysregulated in excitatory and inhibitory neurons, but, rather, because excitatory neurons rely more heavily on inhibition to counterbalance strong excitation. Receptive fields in both cell types have a center-surround organization but disinhibition unmasks more excitatory input to excitatory neurons. Differences in intrinsic excitability also affect how chloride dysregulation affects spiking. These results deepen understanding of how excitation and inhibition are normally balanced in the spinal dorsal horn, and how their imbalance disrupts somatosensory processing.

scholarly journals Metabotropic glutamate receptor 5 regulates excitability and Kv4.2-containing K+ channels primarily in excitatory neurons of the spinal dorsal horn

2011 ◽  
Vol 105 (6) ◽  
pp. 3010-3021 ◽  
Author(s):  
Hui-Juan Hu ◽  
Robert W. Gereau
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Neuronal Excitability ◽  
Gabaergic Neurons ◽  
Erk Signaling ◽  
Metabotropic Glutamate ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Excitatory Neurons

Metabotropic glutamate (mGlu) receptors play important roles in the modulation of nociception. Previous studies demonstrated that mGlu5 modulates nociceptive plasticity via activation of ERK signaling. We have reported recently that the Kv4.2 K+ channel subunit underlies A-type currents in spinal cord dorsal horn neurons and that this channel is modulated by mGlu5-ERK signaling. In the present study, we tested the hypothesis that modulation of Kv4.2 by mGlu5 occurs in excitatory spinal dorsal horn neurons. With the use of a transgenic mouse strain expressing enhanced green fluorescent protein (GFP) under control of the promoter for the γ-amino butyric acid (GABA)-synthesizing enzyme, glutamic acid decarboxylase 67 (GAD67), we found that these GABAergic neurons express less Kv4.2-mediated A-type current than non-GAD67-GFP neurons. Furthermore, the mGlu1/5 agonist, (R,S)-3,5-dihydroxyphenylglycine, had no modulatory effects on A-type currents or neuronal excitability in this subgroup of GABAergic neurons but robustly modulated A-type currents and neuronal excitability in non-GFP-expressing neurons. Immunofluorescence studies revealed that Kv4.2 was highly colocalized with markers of excitatory neurons, such as vesicular glutamate transporter 1/2, PKCγ, and neurokinin 1, in cultured dorsal horn neurons. These results indicate that mGlu5-Kv4.2 signaling is associated with excitatory dorsal horn neurons and suggest that the pronociceptive effects of mGlu5 activation in the spinal cord likely involve enhanced excitability of excitatory neurons.

Vagal afferent stimulation-produced effects on nociception in capsaicin-treated rats

1993 ◽  
Vol 69 (5) ◽  
pp. 1530-1540 ◽  
Author(s):  
K. Ren ◽  
M. Zhuo ◽  
A. Randich ◽  
G. F. Gebhart
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Receptive Fields ◽  
Tail Flick ◽  
Mechanical Stimuli ◽  
Adult Rats ◽  
Afferent Stimulation ◽  
Spinal Dorsal ◽  
Nociceptive Responses ◽  
Vagal Afferent

1. The effects of electrical stimulation of cervical vagal afferent fibers on the nociceptive tail-flick (TF) reflex and responses of spinal dorsal horn neurons to noxious cutaneous stimulation were studied in adult rats treated as neonates with either capsaicin or vehicle. 2. Vagal afferent stimulation (VAS) produced biphasic, intensity-dependent effects on the TF reflex in vehicle-treated and untreated control rats. The TF reflex was facilitated in both groups of rats at lesser intensities of VAS (2.5-50 microA) and fully inhibited at greater intensities of VAS (50-100 microA). In contrast, biphasic effects of VAS on the TF reflex generally were not produced in rats treated as neonates with capsaicin. Facilitation of the TF reflex was produced in these rats by lesser intensities of VAS as well as by typically "inhibitory" intensities of VAS; the TF reflex was never inhibited in 6/12 rats, even at the greatest intensity of VAS tested (1,000 microA). When the TF reflex was inhibited by VAS in capsaicin-treated rats, the intensities required were significantly greater than those required in vehicle-treated or untreated rats. 3. In electrophysiological experiments, 77 neurons were recorded in the lumbar spinal dorsal horn of pentobarbital sodium-anesthetized, paralyzed rats treated as neonates with either vehicle or capsaicin. The neurons had receptive fields on the glabrous skin of the plantar surface of the ipsilateral hind foot, and all responded to mechanical stimuli of both nonnoxious and noxious intensities; 16/77 neurons also responded to noxious thermal stimulation. In vehicle-treated rats, nociceptive responses of 50% of 30 units studied were biphasically modulated by VAS, 33% were only inhibited, and 17% were only facilitated by VAS at the intensities tested (5-500 microA). In capsaicin-treated rats, nociceptive responses of 32% of 47 units studied were biphasically modulated by VAS, 15% were only inhibited, and 34% were only facilitated by VAS at the intensities tested (5-500 microA). In addition, nociceptive responses of neurons facilitated at lesser intensities of VAS and not affected at greater intensities of VAS were observed in capsaicin-treated rats (19% of the 47-unit sample). Overall, the proportion of the neuronal sample inhibited by VAS was less, and the proportion of the sample facilitated by VAS was greater in capsaicin-treated rats compared with vehicle-treated rats. 4. The efficacy of the capsaicin treatment was evaluated immunocytochemically.(ABSTRACT TRUNCATED AT 400 WORDS)

Development of putative inhibitory neurons in the embryonic and postnatal mouse superficial spinal dorsal horn

2016 ◽  
Vol 222 (5) ◽  
pp. 2157-2171 ◽  
Author(s):  
Anita Balázs ◽  
Zoltán Mészár ◽  
Krisztina Hegedűs ◽  
Annamária Kenyeres ◽  
Zoltán Hegyi ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Inhibitory Neurons ◽  
Spinal Dorsal

scholarly journals Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli

Pain ◽  
2017 ◽  
Vol 158 (3) ◽  
pp. 440-456 ◽  
Author(s):  
Maria Gutierrez-Mecinas ◽  
Andrew M. Bell ◽  
Alina Marin ◽  
Rebecca Taylor ◽  
Kieran A. Boyle ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Distinct Population ◽  
Spinal Dorsal ◽  
Excitatory Neurons
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