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.

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.

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.

Recording Temperature Affects the Excitability of Mouse Superficial Dorsal Horn Neurons, In Vitro

2008 ◽  
Vol 99 (5) ◽  
pp. 2048-2059 ◽  
Author(s):  
B. A. Graham ◽  
A. M. Brichta ◽  
R. J. Callister
Keyword(s):  
Spinal Cord ◽  
Elevated Temperature ◽  
Dorsal Horn ◽  
Current Injection ◽  
Resting Membrane Potential ◽  
Temperature Sensitive ◽  
Superficial Dorsal Horn ◽  
Pain Mechanisms

Superficial dorsal horn (SDH) neurons in laminae I–II of the spinal cord play an important role in processing noxious stimuli. These neurons represent a heterogeneous population and are divided into various categories according to their action potential (AP) discharge during depolarizing current injection. We recently developed an in vivo mouse preparation to examine functional aspects of nociceptive processing and AP discharge in SDH neurons and to extend investigation of pain mechanisms to the genetic level of analysis. Not surprisingly, some in vivo data obtained at body temperature (37°C) differed from those generated at room temperature (22°C) in spinal cord slices. In the current study we examine how temperature influences SDH neuron properties by making recordings at 22 and 32°C in transverse spinal cord slices prepared from L3–L5 segments of adult mice (C57Bl/6). Patch-clamp recordings (KCH3SO4 internal) were made from visualized SDH neurons. At elevated temperature all SDH neurons had reduced input resistance and smaller, briefer APs. Resting membrane potential and AP afterhyperpolarization amplitude were temperature sensitive only in subsets of the SDH population. Notably, elevated temperature increased the prevalence of neurons that did not discharge APs during current injection. These reluctant firing neurons expressed a rapid A-type potassium current, which is enhanced at higher temperatures and thus restrains AP discharge. When compared with previously published whole cell recordings obtained in vivo (37°C) our results suggest that, on balance, in vitro data collected at elevated temperature more closely resemble data collected under in vivo conditions.

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

Serotonin Increases the Incidence of Primary Afferent-Evoked Long-Term Depression in Rat Deep Dorsal Horn Neurons

2001 ◽  
Vol 85 (5) ◽  
pp. 1864-1872 ◽  
Author(s):  
Sandra M. Garraway ◽  
Shawn Hochman
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Long Term Potentiation ◽  
Neonatal Rat ◽  
Long Term Depression ◽  
Primary Afferent ◽  
Dorsal Horn Neurons ◽  
Sensory Evoked ◽  
Synaptic Responses

5-hydroxytryptamine (5-HT) is released in spinal cord by descending systems that modulate somatosensory transmission and can potently depress primary afferent-evoked synaptic responses in dorsal horn neurons. Since primary afferent activity-induced long-term potentiation (LTP) may contribute to central sensitization of nociception, we studied the effects of 5-HT on the expression of sensory-evoked LTP and long-term depression (LTD) in deep dorsal horn (DDH) neurons. Whole cell, predominantly current clamp, recordings were obtained from DDH neurons in transverse slices of neonatal rat lumbar spinal cord. The effect of 5-HT on dorsal-root stimulation-evoked synaptic responses was tested before, during, or after high-frequency conditioning stimulation (CS). In most cells (80%), 5-HT caused a depression of the naı̈ve synaptic response. Even though 5-HT depressed evoked responses, CS in the presence of 5-HT was not only still capable of inducing LTD but also increased its incidence from 54% in controls to 88% ( P < 0.001). Activation of ligands selective for 5-HT1A/1B and 5-HT1B, but not 5-HT2A/2C or 5-HT3receptors, best reproduced these actions. 5-HT also potently depressed postconditioning synaptic responses regardless of whether the induced plasticity was LTP or LTD. Our results demonstrate that in addition to depressing the amplitude of evoked sensory input, 5-HT can also control the direction of its long-term modifiability, favoring the expression of LTD. These findings demonstrate cellular mechanisms that may contribute to the descending serotonergic control of nociception.

Sign in / Sign up

Export Citation Format

Share Document