Functional GABAA-Receptor–Mediated Inhibition in the Neonatal Dorsal Horn

2006 ◽  
Vol 95 (6) ◽  
pp. 3893-3897 ◽  
Author(s):  
L. Bremner ◽  
M. Fitzgerald ◽  
M. Baccei
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Spike Activity ◽  
Receptive Fields ◽  
Descending Pathways ◽  
Apparent Lack ◽  
Dorsal Horn Neurons ◽  
Rat Pups ◽  
Sensory Activity

Neonatal nociceptive circuits and dorsal horn cells are characterized by an apparent lack of inhibitory control: receptive fields are large and thresholds low in the first weeks of life. It has been suggested that this may reflect immature GABAA-receptor (GABAAR) signaling whereby an early developmental shift in transmembrane anion gradient is followed by a longer period of low Cl− extrusion capacity. To investigate whether functional GABAAR-mediated inhibition does indeed undergo postnatal regulation at the level of dorsal horn circuits, we applied the selective GABAAR antagonist gabazine to the spinal cord in anesthetized rat pups [postnatal day (P) 3 or 21] while recording spike activity in single lumbar dorsal horn cells in vivo. At both ages, blockade of GABAAR activity resulted in enlarged hind paw receptive field areas and increased activity evoked by low- and high-intensity cutaneous stimulation, revealing comparable inhibition of dorsal horn cell firing by spinal GABAARs at P3 and P21. This inhibition did not require descending pathways to the spinal cord because perforated patch-clamp recordings of deep dorsal horn neurons in P3 spinal cord slices also showed an increase in evoked spike activity after application of gabazine. We conclude that spinal GABAergic inhibitory transmission onto single dorsal horn cells “in vivo” is functional at P3 and that low Cl− extrusion capacity does not restrict GABAergic function over the normal range of evoked sensory activity. The excitability of neonatal spinal sensory circuits could reflect immaturity in other intrinsic or descending inhibitory networks rather than weak spinal GABAergic inhibition.

Developmental Changes in the Fidelity and Short-Term Plasticity of GABAergic Synapses in the Neonatal Rat Dorsal Horn

2008 ◽  
Vol 99 (6) ◽  
pp. 3144-3150 ◽  
Author(s):  
Rachel A. Ingram ◽  
Maria Fitzgerald ◽  
Mark L. Baccei
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Receptive Fields ◽  
Neuronal Firing ◽  
Neonatal Rat ◽  
Superficial Dorsal Horn ◽  
Short Term ◽  
Dorsal Horn Neurons ◽  
Gabaergic Synapses

The lower thresholds and increased excitability of dorsal horn neurons in the neonatal rat suggest that inhibitory processing is less efficient in the immature spinal cord. This is unlikely to be explained by an absence of functional GABAergic inhibition because antagonism of γ-aminobutyric acid (GABA) type A receptors augments neuronal firing in vivo from the first days of life. However, it is possible that more subtle deficits in GABAergic signaling exist in the neonate, such as decreased reliability of transmission or greater depression during repetitive stimulation, both of which could influence the relative excitability of the immature spinal cord. To address this issue we examined monosynaptic GABAergic inputs onto superficial dorsal horn neurons using whole cell patch-clamp recordings made in spinal cord slices at a range of postnatal ages (P3, P10, and P21). The amplitudes of evoked inhibitory postsynaptic currents (IPSCs) were significantly lower and showed greater variability in younger animals, suggesting a lower fidelity of GABAergic signaling at early postnatal ages. Paired-pulse ratios were similar throughout the postnatal period, whereas trains of stimuli (1, 5, 10, and 20 Hz) revealed frequency-dependent short-term depression (STD) of IPSCs at all ages. Although the magnitude of STD did not differ between ages, the recovery from depression was significantly slower at immature GABAergic synapses. These properties may affect the integration of synaptic inputs within developing superficial dorsal horn neurons and thus contribute to their larger receptive fields and enhanced afterdischarge.

Intraaxonal injection of neurobiotin reveals the long-ranging projections of A beta-hair follicle afferent fibers to the cat dorsal horn

1996 ◽  
Vol 76 (1) ◽  
pp. 242-254 ◽  
Author(s):  
P. Wilson ◽  
P. D. Kitchener ◽  
P. J. Snow
Keyword(s):  
Spinal Cord ◽  
Horseradish Peroxidase ◽  
Hair Follicle ◽  
Dorsal Horn ◽  
Receptive Fields ◽  
Dorsal Horn Neurons ◽  
Somatotopic Organization ◽  
Afferent Fibers ◽  
Synaptic Boutons

1. The morphology and somatotopic organization of the spinal arborizations of identified A beta-hair follicle afferent fibers (HFAs) with receptive fields (RFs) on the digits have been investigated in the cat by the use of intraaxonal injection of the tracer n-(2 aminoethyl) biotinamide. 2. In three cats, the long-ranging projections of six HFAs were examined by selectively injecting afferents with RFs on digit 2, 4, or 5, directly over the digit 3 representation, and examining their collateral morphology in transverse sections of the spinal cord. The rostral and caudal boundaries of the digit 3 representation were determined by mapping the RFs of identified spinocervical tract (SCT) neurons. 3. In two more cats, three HFAs were injected at random rostrocaudal positions and their morphology was examined in parasagittal sections. In one animal (2 HFAs), the somatotopy of the digit representation was again determined by mapping the RFs of SCT neurons. In the remaining cat (1 HFA), the somatotopy of the dorsal horn was mapped from the RFs of unidentified dorsal horn neurons. 4. Hair follicle afferents emitted many more collaterals, over much greater rostrocaudal distances, than indicated by previous horseradish peroxidase studies, and all collaterals gave rise to synaptic boutons. 5. HFAs that have RFs confined to a small part of a digit give rise to bouton-bearing axonal branches throughout the entire rostrocaudal extent of the hindpaw representation.

In vivo characterization of colorectal and cutaneous inputs to lumbosacral dorsal horn neurons in the mouse spinal cord

Neuroscience ◽  
2016 ◽  
Vol 316 ◽  
pp. 13-25 ◽  
Author(s):  
K.E. Farrell ◽  
M.M. Rank ◽  
S. Keely ◽  
A.M. Brichta ◽  
B.A. Graham ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Mouse Spinal Cord ◽  
Dorsal Horn Neurons ◽  
In Vivo Characterization

scholarly journals Comparison of the Immediate Effects of Surgical Incision on Dorsal Horn Neuronal Receptive Field Size and Responses during Postnatal Development

2008 ◽  
Vol 109 (4) ◽  
pp. 698-706 ◽  
Author(s):  
Douglas G. Ririe ◽  
Lindsay R. Bremner ◽  
Maria Fitzgerald
Keyword(s):  
Receptive Field ◽  
Dorsal Horn ◽  
Spike Activity ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Skin Incision ◽  
Dorsal Horn Neuron ◽  
Field Size ◽  
Long Term Effects ◽  
Rat Pups

Background Pain behavior in response to skin incision is developmentally regulated, but little is known about the underlying neuronal mechanisms. The authors hypothesize that the spatial activation and intensity of dorsal horn neuron responses to skin incision differ in immature and adult spinal cord. Methods Single wide-dynamic-range dorsal horn cell spike activity was recorded for a minimum of 2 h from anesthetized rat pups aged 7 and 28 days. Cutaneous pinch and brush receptive fields were mapped and von Frey hair thresholds were determined on the plantar hind paw before and 1 h after a skin incision was made. Results Baseline receptive field areas for brush and pinch were larger and von Frey thresholds lower in the younger animals. One hour after the incision, brush and pinch receptive field area, spontaneous firing, and evoked spike activity had significantly increased in the 7-day-old animals but not in the 28-day-old animals. Von Frey hair thresholds decreased at both ages. Conclusions Continuous recording from single dorsal horn cells both before and after injury shows that sensitization of receptive fields and of background and afferent-evoked spike activity at 1 h is greater in younger animals. This difference is not reflected in von Frey mechanical thresholds. These results highlight the importance of studying the effects of injury on sensory neuron physiology. Injury in young animals induces a marked and rapid increase in afferent-evoked activity in second-order sensory neurons, which may be important when considering long-term effects and analgesic interventions.

Control of Size and Excitability of Mechanosensory Receptive Fields in Dorsal Column Nuclei by Homolateral Dorsal Horn Neurons

1998 ◽  
Vol 80 (1) ◽  
pp. 120-129 ◽  
Author(s):  
Robert W. Dykes ◽  
A. D. Craig
Keyword(s):  
Spinal Cord ◽  
Receptive Field ◽  
Dorsal Horn ◽  
Cobalt Chloride ◽  
Receptive Fields ◽  
Dorsal Column ◽  
Field Size ◽  
Dorsal Column Nuclei ◽  
Receptive Field Size ◽  
Dorsal Horn Neurons

Dykes, Robert W. and A. D. Craig. Control of size and excitability of mechanosensory receptive fields in dorsal column nuclei by homolateral dorsal horn neurons. J. Neurophysiol. 80: 120–129 1998. Both accidental and experimental lesions of the spinal cord suggest that neuronal processes occurring in the spinal cord modify the relay of information through the dorsal column-lemniscal pathway. How such interactions might occur has not been adequately explained. To address this issue, the receptive fields of mechanosensory neurons of the dorsal column nuclei were studied before and after manipulation of the spinal dorsal horn. After either a cervical or lumbar laminectomy and exposure of the dorsal column nuclei in anesthetized cats, the representation of the hindlimb or of the forelimb was defined by multiunit recordings in both the dorsal column nuclei and in the ipsilateral spinal cord. Next, a single cell was isolated in the dorsal column nuclei, and its receptive field carefully defined. Each cell could be activated by light mechanical stimuli from a well-defined cutaneous receptive field. Generally the adequate stimulus was movement of a few hairs or rapid skin indentation. Subsequently a pipette containing either lidocaine or cobalt chloride was lowered into the ipsilateral dorsal horn at the site in the somatosensory representation in the spinal cord corresponding to the receptive field of the neuron isolated in the dorsal column nuclei. Injection of several hundred nanoliters of either lidocaine or cobalt chloride into the dorsal horn produced an enlargement of the receptive field of the neuron being studied in the dorsal column nuclei. The experiment was repeated 16 times, and receptive field enlargements of 147–563% were observed in 15 cases. These data suggest that the dorsal horn exerts a tonic inhibitory control on the mechanosensory signals relayed through the dorsal column-lemniscal pathway. Because published data from other laboratories have shown that receptive field size is controlled by signals arising from the skin, we infer that the control of neuronal excitability, receptive field size and location for lemniscal neurons is determined by tonic afferent activity that is relayed through a synapse in the dorsal horn. This influence of dorsal horn neurons on the relay of mechanosensory information through the lemniscal pathways must modify our traditional views concerning the relative independence of these two systems.

scholarly journals In vivo patch-clamp analysis of dopaminergic antinociceptive actions on dorsal horn neurons in the spinal cord

PAIN RESEARCH ◽  
2011 ◽  
Vol 26 (3) ◽  
pp. 137-144
Author(s):  
Wataru Taniguchi ◽  
Terumasa Nakatsuka ◽  
Nobuyuki Miyazaki ◽  
Noboru Takiguchi ◽  
Yae Sugimura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Patch Clamp ◽  
Dorsal Horn ◽  
Dorsal Horn Neurons

scholarly journals Differential Modulation of Dorsal Horn Neurons by Various Spinal Cord Stimulation Strategies

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 568
Author(s):  
Kwan Yeop Lee ◽  
Dongchul Lee ◽  
Zachary B. Kagan ◽  
Dong Wang ◽  
Kerry Bradley
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Spinal Cord Stimulation ◽  
Low Frequency ◽  
Inhibitory Interneurons ◽  
Dependent Manner ◽  
Dorsal Horn Neurons ◽  
Low Intensity ◽  
Mechanistic Basis

New strategies for spinal cord stimulation (SCS) for chronic pain have emerged in recent years, which may work better via different analgesic mechanisms than traditional low-frequency (e.g., 50 Hz) paresthesia-based SCS. To determine if 10 kHz and burst SCS waveforms might have a similar mechanistic basis, we examined whether these SCS strategies at intensities ostensibly below sensory thresholds would modulate spinal dorsal horn (DH) neuronal function in a neuron type-dependent manner. By using an in vivo electrophysiological approach in rodents, we found that low-intensity 10 kHz SCS, but not burst SCS, selectively activates inhibitory interneurons in the spinal DH. This study suggests that low-intensity 10 kHz SCS may inhibit pain-sensory processing in the spinal DH by activating inhibitory interneurons without activating DC fibers, resulting in paresthesia-free pain relief, whereas burst SCS likely operates via other mechanisms.

scholarly journals Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebecca Rani Das Gupta ◽  
Louis Scheurer ◽  
Pawel Pelczar ◽  
Hendrik Wildner ◽  
Hanns Ulrich Zeilhofer
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Functional Organization ◽  
Affinity Purification ◽  
Expression Patterns ◽  
Inhibitory Neurons ◽  
Dorsal Horn Neurons ◽  
Expression Of Genes ◽  
Excitatory Neurons ◽  
Genes Encoding

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (vGluT2+) and inhibitory GABA and/or glycinergic (vGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are not only set apart, as expected, by the expression of genes related to the production, release or re-uptake of their principal neurotransmitters and by genes encoding for transcription factors, but also by a differential engagement of neuromodulator, especially neuropeptide, signaling pathways. Subsequent multiplex in situ hybridization revealed eleven neuropeptide genes that are strongly enriched in excitatory dorsal horn neurons and display largely non-overlapping expression patterns closely adhering to the laminar and presumably also functional organization of the spinal cord grey matter.

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