A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn
© Yasaka et al.; licensee BioMed Central Ltd. 2014
Received: 17 December 2013
Accepted: 14 January 2014
Published: 17 January 2014
Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons. Vertical cells in lamina II provide a potential route through which tactile stimuli can activate lamina I projection neurons, since their dendrites extend into the region where tactile afferents terminate, while their axons can innervate the projection cells. The aim of this study was to determine whether vertical cell dendrites were contacted by the central terminals of low-threshold mechanoreceptive primary afferents.
We initially demonstrated contacts between dendritic spines of vertical cells that had been recorded in spinal cord slices and axonal boutons containing the vesicular glutamate transporter 1 (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive afferents. To confirm that the VGLUT1 boutons included primary afferents, we then examined vertical cells recorded in rats that had received injections of cholera toxin B subunit (CTb) into the sciatic nerve. We found that over half of the VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating that they were of primary afferent origin.
These results show that vertical cell dendritic spines are frequently contacted by the central terminals of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines are associated with excitatory synapses, it is likely that most of these contacts were synaptic. Vertical cells in lamina II are therefore a potential route through which tactile afferents can activate lamina I projection neurons, and this pathway could play a role in tactile allodynia.
Lamina II of the spinal dorsal horn contains numerous densely packed neurons, which have axons that arborise locally and remain within the spinal cord [1, 2]. Between a quarter and a third of these cells are GABAergic/glycinergic inhibitory interneurons [3, 4], while the remainder are excitatory, glutamatergic interneurons [5–7]. Lamina II interneurons are diverse, and numerous attempts have been made to classify them into functional populations, based on morphological, electrophysiological or neurochemical criteria [2, 5, 6, 8–14]. Among the excitatory interneurons, one class that has been recognised in several studies consists of vertical cells, which usually have their cell body in the outer part of the lamina (IIo) and cone-shaped dendritic trees that extend in a ventral direction [5, 6, 9, 11, 13, 15–18]. Many vertical cells have numerous spines, or stalk-like appendages, and these were previously known as stalked cells in studies of the cat spinal cord and spinal trigeminal nucleus [19–21].
Lamina I projection neurons represent a major output from the superficial dorsal horn. They have axons that cross the midline and pass through the contralateral ventral quadrant, constituting a significant part of the ascending anterolateral tract (ALT). They project to a variety of brainstem structures, including the lateral parabrachial area (LPb), periaqueductal grey matter, nucleus of the solitary tract and thalamus [2, 22, 23]. We have shown that the vast majority of lamina I projection neurons in the rat lumbar enlargement can be retrogradely labelled from the LPb [23–25], and the electrophysiological properties of lamina I spinoparabrachial neurons [26–29] are therefore likely to reflect those of all ALT cells in this lamina. Recordings from these cells in anaesthetised rats indicate that virtually all (96–100%) respond to noxious stimuli, with a few also being activated by innocuous mechanical stimulation [26, 28]. Some lamina I projection neurons also respond to pruritic stimuli, and are thus likely to convey information perceived as itch .
Primary afferent input to the dorsal horn is arranged in a highly organised way, with nociceptive and thermoreceptive afferents terminating mainly in laminae I and IIo, while low-threshold mechanoreceptive (LTMR) inputs arborise in a region extending ventrally from the inner half of lamina II (IIi) . It has been reported that the proportion of lamina I projection neurons that respond to low-threshold mechanical stimuli increases following nerve injury , and this is thought to contribute to the tactile allodynia seen in neuropathic pain. Following blockade of spinal inhibitory transmission there is an increased input from large myelinated (Aβ) afferents (presumed LTMRs) to lamina I neurons, and it has been suggested that this is conveyed through polysynaptic pathways involving excitatory interneurons [31, 32].
Vertical cells in lamina II could potentially provide a route through which myelinated LTMR (A-LTMR) primary afferents activate lamina I projection neurons, since their dendrites often extend into the region where these afferents terminate, and their axons frequently arborise in lamina I [5, 6, 9, 17, 19, 20]. The aim of this study was therefore to determine whether vertical cells receive contacts from boutons belonging to A-LTMRs. Since many of these afferents express the vesicular glutamate transporter VGLUT1, and these are the main source of VGLUT1-immunoreactive terminals in this region , we initially looked for contacts between VGLUT1+ boutons and vertical cell dendrites. However, since not all VGLUT1-immunoreactive boutons are of primary afferent origin , we also examined three vertical cells that were identified in rats that had received an injection of cholera toxin B subunit (CTb) into the sciatic nerve, in order to bulk label A-LTMRs.
All animal experiments were approved by the Ethical Review Process Applications Panel of the University of Glasgow or the Saga University Animal Care and Use Committee. They were performed in accordance with the European Community directive 86/609/EC, the UK Animals (Scientific Procedures) Act 1986 and the “Guiding Principles for the Care and Use of Animals in the Field of Physiological Science” of the Physiological Society of Japan.
VGLUT1 contacts on vertical cells
Seven of the glutamatergic vertical cells that were identified in our previous study  were tested for the presence of contacts from VGLUT1-immunoreactive boutons. The cells had been recorded with the blind whole-cell patch-clamp method in sagittal spinal cord slices taken from young adult (6–10 week old) Wistar rats, using Neurobiotin-filled pipettes, as described previously . A single 60 μm thick section that had been reacted with avidin conjugated to Rhodamine Red (1:1000; Jackson Immunoresearch, West Grove, PA, USA) and contained part of the dendritic tree of the recorded cell was taken from each of these slices. This was incubated free-floating in goat antibody against VGLUT1  (1:500), followed by species-specific donkey anti-goat IgG conjugated to Alexa 488 or Alexa 555 (Life Technologies, Paisley, UK; 1:500) or DyLight 649 (Jackson Immunoresearch; 1:500). Sections were scanned with a Zeiss LSM 710 confocal microscope (with Argon multi-line, 405 nm diode, 561 nm solid state and 633 nm HeNe lasers) through a 63× oil-immersion lens (NA 1.4) with the pinhole set to 1 Airy unit, to create image stacks (0.3 or 0.5 μm z-separation) of those parts of the dendritic trees that lay within the plexus of VGLUT1-immunoreactive axons. These image stacks were analysed with Neurolucida for Confocal software (MBF Bioscience; Williston, VT, USA).
The dorsal limit of the dense plexus of VGLUT1 staining, which occupies laminae IIi-VI [33, 36], was initially drawn, and then the VGLUT1 channel was hidden. All dendritic spines belonging to the recorded cells that lay below this limit (i.e. within the VGLUT1 plexus) were identified. The VGLUT1 channel was then switched on, and any VGLUT1-immunoreactive boutons that contacted the spines were recorded.
VGLUT1 contacts on vertical cells in rats that had received sciatic nerve injections
The methods used for injection of CTb into the sciatic nerve, and for obtaining spinal cord slices from adult rats were similar to those described previously [6, 37, 38]. Briefly, 2 male Wistar rats (7 weeks old) were deeply anaesthetized with isoflurane. The left sciatic nerve was exposed and injected with 5 μl of 1% CTb (Sigma-Aldrich, St Louis, MO, USA). Four days later, the animals were deeply anaesthetized with isoflurane. After thoracolumbar laminectomy, the spinal cord was removed into ice-cold dissection solution (mM: NaCl 0, KCl 1.8, KH2PO4 1.2, CaCl2 0.5, MgCl2 7, NaHCO3 26, glucose 15, sucrose 254, oxygenated with 95% O2, 5% CO2). The rats were then killed by anaesthetic overdose and decapitation. All dorsal and ventral roots were removed. The spinal cord was then glued onto an agar block and cut into 500 μm thick parasagittal slices with a microslicer (DTK-1000; Dosaka EM Co., Ltd., Kyoto, Japan). From each rat, a slice that included the sciatic nerve territory of the L4 and L5 segments was selected and transferred to a recording chamber where it was perfused with normal Krebs’ solution (identical to the dissection solution except for (mM): NaCl 127, CaCl2 2.4, MgCl2 1.3 and sucrose 0) at 10 ml min-1 at room temperature. Slices were perfused for at least 30 min before recording. Lamina II was identified as a translucent band across the dorsal horn under a dissecting microscope. Blind whole-cell voltage- or current-clamp recordings were made from neurons in this region as previously described , by using glass pipettes (7–12 MΩ) filled with a solution containing the following (mM): potassium gluconate 120, KCl 20, MgCl2 2, Na2ATP 2, NaGTP 0.5, Hepes 20, EGTA 0.5, and 0.2% Neurobiotin (pH 7.28 adjusted with KOH). Signals were acquired with a patch-clamp amplifier (Axopatch 200B, Molecular Devices, Sunnyvale, CA) and acquisition software (pCLAMP 10, Molecular Devices). Signals were lowpass filtered at 5 kHz, amplified 10-fold in voltage-clamp mode or 50-fold in current-clamp mode, sampled at 10 kHz and analysed offline using pCLAMP 9 or 10. No correction was made for the liquid junction potential.
The resting membrane potential was determined immediately after establishing the whole-cell configuration. Neurons that had a resting membrane potential less negative than -40 mV were not used for electrophysiological recording. The built-in pCLAMP membrane test was used to monitor membrane properties during recording. The protocol used to test firing patterns in this study was based on that described by Sandkühler and co-workers [13, 39, 40]. In our previous study, we found that all excitatory vertical cells showed firing patterns associated with A-type potassium (I A) currents (delayed or reluctant firing) [6, 41]. These firing patterns depend on the holding potential, because removing inactivation of A-type potassium channels requires a hyperpolarized membrane potential. To optimise detection of I A-related firing patterns, we used a standardised protocol that involved testing each cell from three different potentials (one from between -50 and -65 mV, one from between -65 and -80 mV and one from a potential more negative than -80 mV). If an I A-related firing pattern was observed, however, the remaining firing patterns from more negative membrane potentials were not assessed. A voltage step protocol was used to assess the presence of I A, hyperpolarisation-activated currents (H-currents, I h), and currents through low threshold calcium channels (I Ca). The membrane potential was held at -50 mV (or in some cases at -40 or -30 mV) and increasing negative voltage steps of 1 s duration were applied (usually over the range -60 to -140 mV, with 10 mV steps).
The slices from these rats were initially incubated in avidin conjugated to Alexa 488 (Life Technologies; 1:500). They were then cut into 60 μm thick sections with a vibrating microtome, and these were scanned to reveal the morphology of the recorded cells. Three of these were classified as vertical cells, and sections that contained most of the dendritic trees of these cells were incubated for 3 days in a cocktail consisting of guinea pig or rabbit antibody against VGLUT1 (Millipore; 1:5,000 and Synaptic Systems, Göttingen, Germany; 1:5,000, respectively) and goat anti-CTb (List Biological Laboratories, Campbell, CA, USA; 1:500). For one of the cells, several boutons belonging to its axon were present in the section, and for this section guinea pig anti-VGLUT2 (Millipore; 1:5,000) was also included in the primary antibody cocktail. The sections were incubated overnight in species-specific fluorescent secondary antibodies (Jackson Immunoresearch) conjugated to Rhodamine Red, Pacific Blue (both 1:100) or DyLight 649 (1:500). The sections were scanned and analysed in a similar way to that described above, except that in this case, VGLUT1 boutons that contacted dendritic spines of the cells were tested for the presence of CTb-immunoreactivity. For the cell with labelled axonal boutons, we examined these for the presence of VGLUT2-immunoreactivity, which can be used to confirm that the cell is glutamatergic [5, 6, 33, 42].
Characterisation of antibodies
The goat and rabbit VGLUT1 antibodies were raised against the C terminal amino acid sequence (531–560, 456–561, respectively) of the rat protein, and both show a band of the appropriate size on Western blots [35, 43]. The guinea pig anti-VGLUT1 antibody was raised against a 19 amino acid sequence from the rat protein and stains identical structures to the rabbit anti-VGLUT1 . The anti-CTb antibody was raised against the purified protein and specificity was demonstrated by the lack of staining in regions that did not contain transported CTb. The guinea pig VGLUT2 antibody was raised against an 18 amino acid sequence from rat VGLUT2 and stains identical structures to a well-characterised rabbit antibody against VGLUT2 .
Contacts from VGLUT1 boutons onto vertical cells
Contacts from VGLUT1 boutons onto the dendritic spines of 7 vertical cells
Number of spines in VGLUT1 plexus
% spines with VGLUT1 contact
Cell identity in Figure three of Yasaka et al. (2010) 
Vertical cells in rats that received sciatic injections of CTb
The main findings of this study are that excitatory vertical cells in lamina II receive numerous contacts from VGLUT1-immunoreactive boutons on their dendritic spines in laminae IIi and III, and that many of these are primary afferents, as they are labelled with CTb following injection of the tracer into the sciatic nerve.
There is strong evidence that most vertical cells in lamina II are excitatory, since their axons express VGLUT2 [5, 6] and paired recordings have shown that they generate EPSCs in their postsynaptic targets [17, 18]. However, some lamina II neurons that closely resemble glutamatergic vertical cells express the vesicular GABA transporter VGAT, and are therefore inhibitory interneurons [5, 6]. This indicates that morphology alone is not reliable for identifying excitatory vertical cells. We have found a clear difference in firing pattern between these two groups, since the glutamatergic vertical cells showed delayed or reluctant firing patterns, while the inhibitory cells fired tonically . Delayed firing was also a consistent feature of vertical cells that were shown to be excitatory in paired recordings . Although we could not demonstrate VGLUT2 in the axons of two of the cells recorded in the CTb-injected animals (cells 8 and 9 in Table 1), their firing patterns (delayed and reluctant) strongly suggest that these were glutamatergic.
We have previously shown that many VGLUT1-immunoreactive boutons in laminae IIi-III belong to myelinated primary afferents (A-LTMRs), as they can be labelled with CTb injected into a periperal nerve . Consistent with this, Alvarez et al.  found that the majority of VGLUT1-immunoreactive boutons in this region were lost following multiple dorsal rhizotomies. We could not identify primary afferent-derived VGLUT1 boutons in the analysis of the first 7 vertical cells, because these were recorded in animals that had not received CTb injections. However, our findings in the 3 cells from the CTb-injected rats indicate that a significant proportion of the VGLUT1 boutons contacting the vertical cells are of primary afferent origin.
Without electron microscopy, it is not possible to confirm that the contacts we observed were synapses. However, dendritic spines are commonly associated with excitatory synapses and A-LTMRs often form the central boutons of synaptic glomeruli, which are presynaptic to several dendritic spines . It is therefore likely that many of these contacts were associated with glutamatergic synapses. Although we saw numerous contacts between VGLUT1-immunoreactive boutons and the dendritic shafts of vertical cells, it is not clear whether these respresent synaptic contacts, because most of the postsynaptic structures in synaptic glomeruli are dendritic spines, rather than shafts . For this reason, we did not quantify contacts onto dendritic shafts of the recorded neurons.
Synaptic input to vertical cells
Electrophysiological studies in spinal cord slices have shown that vertical cells receive monosynaptic input from Aδ and C fibres [9, 11, 17], but could not reveal the receptive field properties of these afferents. It is not yet known which types of C fibre innervate these cells, but they are likely to include nociceptive afferents that express TRPV1, TRPA1 and/or Mas-related G protein-coupled receptor D (Mrgd) [15, 16]. Bennett et al.  provided evidence that stalked cells in the cat are innervated by myelinated nociceptors, and the monosynaptic Aδ input to vertical cells is therefore likely to arise at least in part from Aδ nociceptors, which either terminate in lamina I/IIo or arborise diffusely throughout laminae I-V [55, 56]. However, our results suggest that some of the monosynaptic Aδ input may originate from D-hair afferents, which express VGLUT1  and project to laminae IIi-III [55, 57, 58], a region that is often penetrated by vertical cell dendrites. Gobel et al.  carried out an ultrastructural analysis of a lamina II stalked cell recorded in vivo in the cat, and reported that its dendritic spines received numerous synapses from the central axons of synaptic glomeruli. Interestingly, one of these central axons was particularly large, contained numerous mitochondria and had clusters of loosely-packed synaptic vesicles. This closely resembles the type II glomerular central endings identified in rat, which are thought to originate from Aδ D-hair afferents [54, 59].
Aβ LTMRs, all of which express VGLUT1 [33, 36], terminate throughout the deep dorsal horn (laminae III-VI), with some hair afferents and rapidly adapting afferents from glabrous skin penetrating into lamina IIi [57, 58, 60–63]. It is therefore possible that some of the contacts that vertical cell dendrites received from VGLUT1-immunoreactive boutons could represent synapses from Aβ LTMRs. Many studies have used electrical stimulation of dorsal roots to investigate primary afferent input to lamina II neurons in slice preparations, but very few of these neurons have been found to receive monosynaptic input from Aβ fibres [9, 11, 13, 64–67]. However, this may be at least in part because of the difficulty of retaining these afferents intact in spinal cord slices. Aβ fibres have a complex projection, with collaterals arising from long branches that are orientated rostrocaudally in the dorsal columns. Many of these collaterals then pass through the dorsal horn or the medial part of the dorsal columns before curving laterally and entering laminae IIi-III from the deep aspect . The preparation of the transverse, parasagittal or horizontal slices that were used in these studies, may therefore have disrupted the continuity between many Aβ LTMR boutons and their parent axons in the dorsal root, and could lead to failure to detect monosynaptic Aβ input. It is also possible that there were synapses between functionally intact Aβ LTMRs and vertical cells in these slice preparations, but that these were ineffective, either because they were silent [68, 69], or because the resulting EPSCs were highly attenuated due to their distal location. One way to determine whether Aβ LTMRs synapse directly on vertical cells would be to record from these cells in slices from mice expressing green fluorescent protein (GFP) under control of the Npy2R promoter, in which central arborisations of Aβ afferents can be visualised directly through their expression of GFP .
Taken together, these observations suggest that vertical cells are innervated by a variety of different types of myelinated and unmyelinated primary afferents, including both nociceptors and LTMRs. Consistent with this interpretation, although some of the stalked cells recorded in vivo in the cat were nociceptive-specific, others had wide dynamic range receptive fields and responded to deflection of hairs .
Each of the vertical cells from animals that had received sciatic injections of CTb was contacted by boutons that were VGLUT1+/CTb-. While many of these could have belonged to myelinated afferents that had not taken up the injected tracer, some were located in lamina IIo, an area that contains virtually no labelled axons after CTb injection. Central terminals of unmyelinated primary afferents do not appear to contain detectable levels of VGLUT1 [33, 36, 44, 70], but it is possible that these VGLUT1 boutons belong to a type of myelinated primary afferent that does not transport CTb (e.g. the nociceptors that terminate diffusely in laminae I-V ). An alternative explanation is that they are derived from corticospinal tract axons, which express VGLUT1  and terminate in the superficial dorsal horn . This raises the possibility that vertical cells are involved in the cortical modulation of pain pathways.
In addition to their primary afferent inputs, there is evidence that at least two classes of interneuron in lamina II are presynaptic to vertical cells. Lu and Perl  demonstrated excitatory inputs from transient central cells, while Zheng et al.  reported inhibitory inputs from cells expressing GFP under control of the Prion promoter (PrP-GFP cells).
The role of vertical cells in sensory pathways
Gobel and colleagues were the first to suggest that stalked cells provided excitatory input to projection neurons in lamina I, since their axons can arborise extensively in this lamina [20, 21]. Lu and Perl  provided direct support for this suggestion, by demonstrating monosynaptic excitatory connections from vertical cells to lamina I neurons, some of which were retrogradely labelled from rostral thoracic spinal cord. Further evidence was provided by Cordero-Erausquin et al. , who observed numerous vertical/stalked cells that were labelled with a method that allowed transfer of GFP to cells that were presynaptic to lamina I spinoparabrachial neurons. However, lamina I projection neurons are clearly not the only postsynaptic target for vertical cells, since their dendrites generally remain in this lamina [72–76], while the axons of vertical cells can arborise in laminae I, II and III. In addition, not all vertical cells have axons that can be followed into lamina I [6, 9]. There is apparently no information about other potential targets, but these presumably include local interneurons, and possibly the dorsal dendrites of large ALT projection neurons in deeper laminae . In addition to their fast synaptic actions, vertical cells may also give rise to slower, peptide-mediated, effects. We have reported that some vertical cells express somatostatin , which will act on the sst2A receptors that are expressed by around half of the inhibitory interneurons in this region [3, 10, 78, 79]. Interestingly, all of the PrP-GFP cells express sst2A , and somatostatin released from vertical cells may therefore suppress their inhibitory input from this class of interneuron .
Some forms of tactile allodynia in neuropathic pain are evoked by activation of myelinated LTMRs [81, 82], and it is thought that loss of inhibition in the dorsal horn is an important contributor to neuropathic pain [83–86], although there is debate about the underlying mechanisms [4, 65, 87–91]. Torsney and McDermott  proposed that disinhibition could open up a polysynaptic pathway that connected myelinated LTMRs to lamina I neurons, leading to allodynia as a result of increased low-threshold drive to projection cells that are normally activated mainly by nociceptive inputs. They represented this diagramatically as a chain of excitatory interneurons that extended dorsally from lamina III, where most A-LTMR afferents terminate, because there is little evidence for lamina III interneurons with significant axonal projections to lamina I . Consistent with this suggestion, Lu et al.  have recently provided evidence for a polysynaptic pathway involving PKCγ-expressing excitatory interneurons in laminae IIi-III  that are directly innervated by Aβ afferents and activate a class of excitatory interneuron in lamina II (transient central cells), which in turn excite vertical cells. They proposed that this circuit was under feed-forward inhibition from glycinergic neurons in lamina III, and that following spinal nerve ligation , the inhibition was reduced, leading to strengthening of polysynaptic Aβ pathways . However, it is not clear whether this would contribute to tactile allodynia, since these changes were observed in the L5 segment (which had input from damaged primary afferents), but not following stimulation of the L4 root, which is thought to be responsible for conveying inputs that give rise to allodynia in this model .
The present results suggest that in addition to their nociceptive input, lamina II vertical cells may receive synapses from myelinated low-threshold mechanoreceptors on their ventral dendrites. Vertical cells could therefore sample a diverse range of sensory input, and serve to integrate this before transmitting it to projection neurons in lamina I. Strengthening of this putative disynaptic pathway between tactile afferents and projection cells could contribute to the allodynia seen in neuropathic pain.
Cholera toxin B subunit
Green fluorescent protein
A-type potassium current
Lateral parabrachial area
Vesicular glutamate transporter 1
Vesicular glutamate transporter 2.
We are grateful to Mr R Kerr and Ms C Watt for excellent technical assistance. The work was supported by the Wellcome Trust, the BBSRC and JSPS KAKENHI (Grant Number 23659320).
- Rexed B: The cytoarchitectonic organization of the spinal cord in the cat. J Comp Neurol 1952, 96: 414–495.PubMed
- Todd AJ: Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci 2010, 11: 823–836. 10.1038/nrn2947PubMed CentralPubMedView Article
- Polgar E, Durrieux C, Hughes DI, Todd AJ: A quantitative study of inhibitory interneurons in laminae I-III of the mouse spinal dorsal horn. PLoS One 2013, 8: e78309. 10.1371/journal.pone.0078309PubMed CentralPubMedView Article
- Polgár E, Hughes DI, Riddell JS, Maxwell DJ, Puskar Z, Todd AJ: Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain. Pain 2003, 104: 229–239. 10.1016/S0304-3959(03)00011-3PubMedView Article
- Maxwell DJ, Belle MD, Cheunsuang O, Stewart A, Morris R: Morphology of inhibitory and excitatory interneurons in superficial laminae of the rat dorsal horn. J Physiol 2007, 584: 521–533. 10.1113/jphysiol.2007.140996PubMed CentralPubMedView Article
- Yasaka T, Tiong SYX, Hughes DI, Riddell JS, Todd AJ: Populations of inhibitory and excitatory interneurons in lamina II of the adult rat spinal dorsal horn revealed by a combined electrophysiological and anatomical approach. Pain 2010, 151: 475–488. 10.1016/j.pain.2010.08.008PubMed CentralPubMedView Article
- Yoshimura M, Nishi S: Excitatory amino acid receptors involved in primary afferent-evoked polysynaptic EPSPs of substantia gelatinosa neurons in the adult rat spinal cord slice. Neurosci Lett 1992, 143: 131–134. 10.1016/0304-3940(92)90249-7PubMedView Article
- Graham BA, Brichta AM, Callister RJ: Moving from an averaged to specific view of spinal cord pain processing circuits. J Neurophysiol 2007, 98: 1057–1063. 10.1152/jn.00581.2007PubMedView Article
- Grudt TJ, Perl ER: Correlations between neuronal morphology and electrophysiological features in the rodent superficial dorsal horn. J Physiol 2002, 540: 189–207. 10.1113/jphysiol.2001.012890PubMed CentralPubMedView Article
- Polgár E, Sardella TCP, Tiong SYX, Locke S, Watanabe M, Todd AJ: Functional differences between neurochemically-defined populations of inhibitory interneurons in the rat spinal cord. Pain 2013, 154: 2606–2615. 10.1016/j.pain.2013.05.001PubMed CentralPubMedView Article
- Yasaka T, Kato G, Furue H, Rashid MH, Sonohata M, Tamae A, Murata Y, Masuko S, Yoshimura M: Cell-type-specific excitatory and inhibitory circuits involving primary afferents in the substantia gelatinosa of the rat spinal dorsal horn in vitro. J Physiol 2007, 581: 603–618. 10.1113/jphysiol.2006.123919PubMed CentralPubMedView Article
- Santos SF, Rebelo S, Derkach VA, Safronov BV: Excitatory interneurons dominate sensory processing in the spinal substantia gelatinosa of rat. J Physiol 2007, 581: 241–254. 10.1113/jphysiol.2006.126912PubMed CentralPubMedView Article
- Heinke B, Ruscheweyh R, Forsthuber L, Wunderbaldinger G, Sandkuhler J: Physiological, neurochemical and morphological properties of a subgroup of GABAergic spinal lamina II neurones identified by expression of green fluorescent protein in mice. J Physiol 2004, 560: 249–266. 10.1113/jphysiol.2004.070540PubMed CentralPubMedView Article
- Zeilhofer HU, Wildner H, Yevenes GE: Fast synaptic inhibition in spinal sensory processing and pain control. Physiol Rev 2012, 92: 193–235. 10.1152/physrev.00043.2010PubMed CentralPubMedView Article
- Uta D, Furue H, Pickering AE, Rashid MH, Mizuguchi-Takase H, Katafuchi T, Imoto K, Yoshimura M: TRPA1-expressing primary afferents synapse with a morphologically identified subclass of substantia gelatinosa neurons in the adult rat spinal cord. Eur J Neurosci 2010, 31: 1960–1973. 10.1111/j.1460-9568.2010.07255.xPubMed CentralPubMedView Article
- Wang H, Zylka MJ: Mrgprd-expressing polymodal nociceptive neurons innervate most known classes of substantia gelatinosa neurons. J Neurosci 2009, 29: 13202–13209. 10.1523/JNEUROSCI.3248-09.2009PubMed CentralPubMedView Article
- Lu Y, Perl ER: Modular organization of excitatory circuits between neurons of the spinal superficial dorsal horn (laminae I and II). J Neurosci 2005, 25: 3900–3907. 10.1523/JNEUROSCI.0102-05.2005PubMedView Article
- Zheng J, Lu Y, Perl ER: Inhibitory neurones of the spinal substantia gelatinosa mediate interaction of signals from primary afferents. J Physiol 2010, 588: 2065–2075. 10.1113/jphysiol.2010.188052PubMed CentralPubMedView Article
- Bennett GJ, Abdelmoumene M, Hayashi H, Dubner R: Physiology and morphology of substantia gelatinosa neurons intracellularly stained with horseradish peroxidase. J Comp Neurol 1980, 194: 809–827. 10.1002/cne.901940407PubMedView Article
- Gobel S: Golgi studies of the neurons in layer II of the dorsal horn of the medulla (trigeminal nucleus caudalis). J Comp Neurol 1978, 180: 395–413. 10.1002/cne.901800213PubMedView Article
- Gobel S, Falls WM, Bennett GJ, Abdelmoumene M, Hayashi H, Humphrey E: An EM analysis of the synaptic connections of horseradish peroxidase-filled stalked cells and islet cells in the substantia gelatinosa of adult cat spinal cord. J Comp Neurol 1980, 194: 781–807. 10.1002/cne.901940406PubMedView Article
- Al-Khater KM, Todd AJ: Collateral projections of neurons in laminae I, III, and IV of rat spinal cord to thalamus, periaqueductal gray matter, and lateral parabrachial area. J Comp Neurol 2009, 515: 629–646. 10.1002/cne.22081PubMed CentralPubMedView Article
- Polgár E, Wright LL, Todd AJ: A quantitative study of brainstem projections from lamina I neurons in the cervical and lumbar enlargement of the rat. Brain Res 2010, 1308: 58–67.PubMed CentralPubMedView Article
- Al Ghamdi KS, Polgar E, Todd AJ: Soma size distinguishes projection neurons from neurokinin 1 receptor-expressing interneurons in lamina I of the rat lumbar spinal dorsal horn. Neuroscience 2009, 164: 1794–1804. 10.1016/j.neuroscience.2009.09.071PubMed CentralPubMedView Article
- Spike RC, Puskar Z, Andrew D, Todd AJ: A quantitative and morphological study of projection neurons in lamina I of the rat lumbar spinal cord. Eur J Neurosci 2003, 18: 2433–2448. 10.1046/j.1460-9568.2003.02981.xPubMedView Article
- Andrew D: Sensitization of lamina I spinoparabrachial neurons parallels heat hyperalgesia in the chronic constriction injury model of neuropathic pain. J Physiol 2009, 587: 2005–2017. 10.1113/jphysiol.2009.170290PubMed CentralPubMedView Article
- Andrew D: Quantitative characterization of low-threshold mechanoreceptor inputs to lamina I spinoparabrachial neurons in the rat. J Physiol 2010, 588: 117–124. 10.1113/jphysiol.2009.181511PubMed CentralPubMedView Article
- Bester H, Chapman V, Besson JM, Bernard JF: Physiological properties of the lamina I spinoparabrachial neurons in the rat. J Neurophysiol 2000, 83: 2239–2259.PubMed
- Keller AF, Beggs S, Salter MW, De Koninck Y: Transformation of the output of spinal lamina I neurons after nerve injury and microglia stimulation underlying neuropathic pain. Mol Pain 2007, 3: 27. 10.1186/1744-8069-3-27PubMed CentralPubMedView Article
- Davidson S, Giesler GJ: The multiple pathways for itch and their interactions with pain. Trends Neurosci 2010, 33: 550–558. 10.1016/j.tins.2010.09.002PubMed CentralPubMedView Article
- Torsney C, MacDermott AB: Disinhibition opens the gate to pathological pain signaling in superficial neurokinin 1 receptor-expressing neurons in rat spinal cord. J Neurosci 2006, 26: 1833–1843. 10.1523/JNEUROSCI.4584-05.2006PubMedView Article
- Lu Y, Dong H, Gao Y, Gong Y, Ren Y, Gu N, Zhou S, Xia N, Sun YY, Ji RR, Xiong L: A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia. J Clin Invest 2013, 123: 4050–4062. 10.1172/JCI70026PubMed CentralPubMedView Article
- Todd AJ, Hughes DI, Polgar E, Nagy GG, Mackie M, Ottersen OP, Maxwell DJ: The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn. Eur J Neurosci 2003, 17: 13–27. 10.1046/j.1460-9568.2003.02406.xPubMedView Article
- Du Beau A, Shakya Shrestha S, Bannatyne BA, Jalicy SM, Linnen S, Maxwell DJ: Neurotransmitter phenotypes of descending systems in the rat lumbar spinal cord. Neuroscience 2012, 227: 67–79.PubMedView Article
- Kawamura Y, Fukaya M, Maejima T, Yoshida T, Miura E, Watanabe M, Ohno-Shosaku T, Kano M: The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. J Neurosci 2006, 26: 2991–3001. 10.1523/JNEUROSCI.4872-05.2006PubMedView Article
- Alvarez FJ, Villalba RM, Zerda R, Schneider SP: Vesicular glutamate transporters in the spinal cord, with special reference to sensory primary afferent synapses. J Comp Neurol 2004, 472: 257–280. 10.1002/cne.20012PubMedView Article
- Naim MM, Shehab SA, Todd AJ: Cells in laminae III and IV of the rat spinal cord which possess the neurokinin-1 receptor receive monosynaptic input from myelinated primary afferents. Eur J Neurosci 1998, 10: 3012–3019. 10.1111/j.1460-9568.1998.00335.xPubMedView Article
- Shehab SA, Spike RC, Todd AJ: Evidence against cholera toxin B subunit as a reliable tracer for sprouting of primary afferents following peripheral nerve injury. Brain Res 2003, 964: 218–227. 10.1016/S0006-8993(02)04001-5PubMedView Article
- Ruscheweyh R, Ikeda H, Heinke B, Sandkuhler J: Distinctive membrane and discharge properties of rat spinal lamina I projection neurones in vitro. J Physiol 2004, 555: 527–543. 10.1113/jphysiol.2003.054049PubMed CentralPubMedView Article
- Ruscheweyh R, Sandkuhler J: Lamina-specific membrane and discharge properties of rat spinal dorsal horn neurones in vitro. J Physiol 2002, 541: 231–244. 10.1113/jphysiol.2002.017756PubMed CentralPubMedView Article
- Graham BA, Brichta AM, Callister RJ: Pinch-current injection defines two discharge profiles in mouse superficial dorsal horn neurones, in vitro. J Physiol 2007, 578: 787–798. 10.1113/jphysiol.2006.123349PubMed CentralPubMedView Article
- Schneider SP, Walker TM: Morphology and electrophysiological properties of hamster spinal dorsal horn neurons that express VGLUT2 and enkephalin. J Comp Neurol 2007, 501: 790–809. 10.1002/cne.21292PubMedView Article
- Takamori S, Rhee JS, Rosenmund C, Jahn R: Identification of differentiation-associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT2). J Neurosci 2001, 21: RC182.PubMed
- Brumovsky P, Watanabe M, Hokfelt T: Expression of the vesicular glutamate transporters-1 and -2 in adult mouse dorsal root ganglia and spinal cord and their regulation by nerve injury. Neuroscience 2007, 147: 469–490. 10.1016/j.neuroscience.2007.02.068PubMedView Article
- Landry M, Bouali-Benazzouz R, El Mestikawy S, Ravassard P, Nagy F: Expression of vesicular glutamate transporters in rat lumbar spinal cord, with a note on dorsal root ganglia. J Comp Neurol 2004, 468: 380–394. 10.1002/cne.10988PubMedView Article
- Llewellyn-Smith IJ, Martin CL, Fenwick NM, Dicarlo SE, Lujan HL, Schreihofer AM: VGLUT1 and VGLUT2 innervation in autonomic regions of intact and transected rat spinal cord. J Comp Neurol 2007, 503: 741–767. 10.1002/cne.21414PubMedView Article
- Oliveira AL, Hydling F, Olsson E, Shi T, Edwards RH, Fujiyama F, Kaneko T, Hokfelt T, Cullheim S, Meister B: Cellular localization of three vesicular glutamate transporter mRNAs and proteins in rat spinal cord and dorsal root ganglia. Synapse 2003, 50: 117–129. 10.1002/syn.10249PubMedView Article
- Persson S, Boulland JL, Aspling M, Larsson M, Fremeau RT Jr, Edwards RH, Storm-Mathisen J, Chaudhry FA, Broman J: Distribution of vesicular glutamate transporters 1 and 2 in the rat spinal cord, with a note on the spinocervical tract. J Comp Neurol 2006, 497: 683–701. 10.1002/cne.20987PubMedView Article
- Varoqui H, Schafer MK, Zhu H, Weihe E, Erickson JD: Identification of the differentiation-associated Na+/PI transporter as a novel vesicular glutamate transporter expressed in a distinct set of glutamatergic synapses. J Neurosci 2002, 22: 142–155.PubMed
- Robertson B, Grant G: A comparison between wheat germ agglutinin-and choleragenoid-horseradish peroxidase as anterogradely transported markers in central branches of primary sensory neurones in the rat with some observations in the cat. Neuroscience 1985, 14: 895–905. 10.1016/0306-4522(85)90152-6PubMedView Article
- LaMotte CC, Kapadia SE, Shapiro CM: Central projections of the sciatic, saphenous, median, and ulnar nerves of the rat demonstrated by transganglionic transport of choleragenoid-HRP (B-HRP) and wheat germ agglutinin-HRP (WGA-HRP). J Comp Neurol 1991, 311: 546–562. 10.1002/cne.903110409PubMedView Article
- Woolf CJ, Shortland P, Reynolds M, Ridings J, Doubell T, Coggeshall RE: Reorganization of central terminals of myelinated primary afferents in the rat dorsal horn following peripheral axotomy. J Comp Neurol 1995, 360: 121–134. 10.1002/cne.903600109PubMedView Article
- Rivero-Melian C, Grant G: Distribution of lumbar dorsal root fibers in the lower thoracic and lumbosacral spinal cord of the rat studied with choleragenoid horseradish peroxidase conjugate. J Comp Neurol 1990, 299: 470–481. 10.1002/cne.902990407PubMedView Article
- Ribeiro-da-Silva A, Coimbra A: Two types of synaptic glomeruli and their distribution in laminae I-III of the rat spinal cord. J Comp Neurol 1982, 209: 176–186. 10.1002/cne.902090205PubMedView Article
- Light AR, Perl ER: Spinal termination of functionally identified primary afferent neurons with slowly conducting myelinated fibers. J Comp Neurol 1979, 186: 133–150. 10.1002/cne.901860203PubMedView Article
- Woodbury CJ, Koerber HR: Widespread projections from myelinated nociceptors throughout the substantia gelatinosa provide novel insights into neonatal hypersensitivity. J Neurosci 2003, 23: 601–610.PubMed
- Abraira VE, Ginty DD: The sensory neurons of touch. Neuron 2013, 79: 618–639. 10.1016/j.neuron.2013.07.051PubMedView Article
- Li L, Rutlin M, Abraira VE, Cassidy C, Kus L, Gong S, Jankowski MP, Luo W, Heintz N, Koerber HR, et al.: The functional organization of cutaneous low-threshold mechanosensory neurons. Cell 2011, 147: 1615–1627. 10.1016/j.cell.2011.11.027PubMed CentralPubMedView Article
- Ribeiro-da-Silva A, Coimbra A: Capsaicin causes selective damage to type I synaptic glomeruli in rat substantia gelatinosa. Brain Res 1984, 290: 380–383. 10.1016/0006-8993(84)90961-2PubMedView Article
- Brown AG, Fyffe RE, Rose PK, Snow PJ: Spinal cord collaterals from axons of type II slowly adapting units in the cat. J Physiol 1981, 316: 469–480.PubMed CentralPubMedView Article
- Shortland P, Woolf CJ: Morphology and somatotopy of the central arborizations of rapidly adapting glabrous skin afferents in the rat lumbar spinal cord. J Comp Neurol 1993, 329: 491–511. 10.1002/cne.903290406PubMedView Article
- Shortland P, Woolf CJ, Fitzgerald M: Morphology and somatotopic organization of the central terminals of hindlimb hair follicle afferents in the rat lumbar spinal cord. J Comp Neurol 1989, 289: 416–433. 10.1002/cne.902890307PubMedView Article
- Hughes DI, Scott DT, Todd AJ, Riddell JS: Lack of evidence for sprouting of Abeta afferents into the superficial laminas of the spinal cord dorsal horn after nerve section. J Neurosci 2003, 23: 9491–9499.PubMed
- Kohno T, Moore KA, Baba H, Woolf CJ: Peripheral nerve injury alters excitatory synaptic transmission in lamina II of the rat dorsal horn. J Physiol 2003, 548: 131–138. 10.1113/jphysiol.2002.036186PubMed CentralPubMedView Article
- Moore KA, Kohno T, Karchewski LA, Scholz J, Baba H, Woolf CJ: Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J Neurosci 2002, 22: 6724–6731.PubMed
- Yoshimura M, Jessell TM: Primary afferent-evoked synaptic responses and slow potential generation in rat substantia gelatinosa neurons in vitro. J Neurophysiol 1989, 62: 96–108.PubMed
- Nakatsuka T, Ataka T, Kumamoto E, Tamaki T, Yoshimura M: Alteration in synaptic inputs through C-afferent fibers to substantia gelatinosa neurons of the rat spinal dorsal horn during postnatal development. Neuroscience 2000, 99: 549–556. 10.1016/S0306-4522(00)00224-4PubMedView Article
- Bardoni R, Magherini PC, MacDermott AB: NMDA EPSCs at glutamatergic synapses in the spinal cord dorsal horn of the postnatal rat. J Neurosci 1998, 18: 6558–6567.PubMed
- Li P, Zhuo M: Silent glutamatergic synapses and nociception in mammalian spinal cord. Nature 1998, 393: 695–698. 10.1038/31496PubMedView Article
- Seal RP, Wang X, Guan Y, Raja SN, Woodbury CJ, Basbaum AI, Edwards RH: Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors. Nature 2009, 462: 651–655. 10.1038/nature08505PubMed CentralPubMedView Article
- Casale EJ, Light AR, Rustioni A: Direct projection of the corticospinal tract to the superficial laminae of the spinal cord in the rat. J Comp Neurol 1988, 278: 275–286. 10.1002/cne.902780210PubMedView Article
- Cordero-Erausquin M, Allard S, Dolique T, Bachand K, Ribeiro-da-Silva A, De Koninck Y: Dorsal horn neurons presynaptic to lamina I spinoparabrachial neurons revealed by transynaptic labeling. J Comp Neurol 2009, 517: 601–615. 10.1002/cne.22179PubMedView Article
- Lima D, Coimbra A: Morphological types of spinomesencephalic neurons in the marginal zone (lamina I) of the rat spinal cord, as shown after retrograde labelling with cholera toxin subunit B. J Comp Neurol 1989, 279: 327–339. 10.1002/cne.902790212PubMedView Article
- Zhang ET, Han ZS, Craig AD: Morphological classes of spinothalamic lamina I neurons in the cat. J Comp Neurol 1996, 367: 537–549. 10.1002/(SICI)1096-9861(19960415)367:4<537::AID-CNE5>3.0.CO;2-5PubMedView Article
- Almarestani L, Waters SM, Krause JE, Bennett GJ, Ribeiro-da-Silva A: Morphological characterization of spinal cord dorsal horn lamina I neurons projecting to the parabrachial nucleus in the rat. J Comp Neurol 2007, 504: 287–297. 10.1002/cne.21410PubMedView Article
- Todd AJ, Puskar Z, Spike RC, Hughes C, Watt C, Forrest L: Projection neurons in lamina I of rat spinal cord with the neurokinin 1 receptor are selectively innervated by substance P-containing afferents and respond to noxious stimulation. J Neurosci 2002, 22: 4103–4113.PubMed
- Naim M, Spike RC, Watt C, Shehab SA, Todd AJ: Cells in laminae III and IV of the rat spinal cord that possess the neurokinin-1 receptor and have dorsally directed dendrites receive a major synaptic input from tachykinin-containing primary afferents. J Neurosci 1997, 17: 5536–5548.PubMed
- Todd AJ, Spike RC, Polgar E: A quantitative study of neurons which express neurokinin-1 or somatostatin sst2a receptor in rat spinal dorsal horn. Neuroscience 1998, 85: 459–473. 10.1016/S0306-4522(97)00669-6PubMedView Article
- Nakatsuka T, Fujita T, Inoue K, Kumamoto E: Activation of GIRK channels in substantia gelatinosa neurones of the adult rat spinal cord: a possible involvement of somatostatin. J Physiol 2008, 586: 2511–2522. 10.1113/jphysiol.2007.146076PubMed CentralPubMedView Article
- Iwagaki N, Garzillo F, Polgar E, Riddell JS, Todd AJ: Neurochemical characterisation of lamina II inhibitory interneurons that express GFP in the PrP-GFP mouse. Mol Pain 2013, 9: 56. 10.1186/1744-8069-9-56PubMed CentralPubMedView Article
- Campbell JN, Raja SN, Meyer RA, Mackinnon SE: Myelinated afferents signal the hyperalgesia associated with nerve injury. Pain 1988, 32: 89–94. 10.1016/0304-3959(88)90027-9PubMedView Article
- Ochoa JL, Yarnitsky D: Mechanical hyperalgesias in neuropathic pain patients: dynamic and static subtypes. Ann Neurol 1993, 33: 465–472. 10.1002/ana.410330509PubMedView Article
- Hwang JH, Yaksh TL: The effect of spinal GABA receptor agonists on tactile allodynia in a surgically-induced neuropathic pain model in the rat. Pain 1997, 70: 15–22. 10.1016/S0304-3959(96)03249-6PubMedView Article
- Malan TP, Mata HP, Porreca F: Spinal GABA(A) and GABA(B) receptor pharmacology in a rat model of neuropathic pain. Anesthesiology 2002, 96: 1161–1167. 10.1097/00000542-200205000-00020PubMedView Article
- Sivilotti L, Woolf CJ: The contribution of GABAA and glycine receptors to central sensitization: disinhibition and touch-evoked allodynia in the spinal cord. J Neurophysiol 1994, 72: 169–179.PubMed
- Miraucourt LS, Moisset X, Dallel R, Voisin DL: Glycine inhibitory dysfunction induces a selectively dynamic, morphine-resistant, and neurokinin 1 receptor- independent mechanical allodynia. J Neurosci 2009, 29: 2519–2527. 10.1523/JNEUROSCI.3923-08.2009PubMedView Article
- Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y: BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005, 438: 1017–1021. 10.1038/nature04223PubMedView Article
- Scholz J, Broom DC, Youn DH, Mills CD, Kohno T, Suter MR, Moore KA, Decosterd I, Coggeshall RE, Woolf CJ: Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury. J Neurosci 2005, 25: 7317–7323. 10.1523/JNEUROSCI.1526-05.2005PubMedView Article
- Yowtak J, Wang J, Kim HY, Lu Y, Chung K, Chung JM: Effect of antioxidant treatment on spinal GABA neurons in a neuropathic pain model in the mouse. Pain 2013, 154: 2469–2476. 10.1016/j.pain.2013.07.024PubMedView Article
- Ibuki T, Hama AT, Wang XT, Pappas GD, Sagen J: Loss of GABA-immunoreactivity in the spinal dorsal horn of rats with peripheral nerve injury and promotion of recovery by adrenal medullary grafts. Neuroscience 1997, 76: 845–858.PubMedView Article
- Polgár E, Todd AJ: Tactile allodynia can occur in the spared nerve injury model in the rat without selective loss of GABA or GABA(A) receptors from synapses in laminae I-II of the ipsilateral spinal dorsal horn. Neuroscience 2008, 156: 193–202. 10.1016/j.neuroscience.2008.07.009PubMed CentralPubMedView Article
- Schneider SP: Functional properties and axon terminations of interneurons in laminae III-V of the mammalian spinal dorsal horn in vitro. J Neurophysiol 1992, 68: 1746–1759.PubMed
- Polgár E, Fowler JH, McGill MM, Todd AJ: The types of neuron which contain protein kinase C gamma in rat spinal cord. Brain Res 1999, 833: 71–80. 10.1016/S0006-8993(99)01500-0PubMedView Article
- Kim SH, Chung JM: An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992, 50: 355–363. 10.1016/0304-3959(92)90041-9PubMedView Article
- Todd AJ: How to recognise collateral damage in partial nerve injury models of neuropathic pain. Pain 2012, 153: 11–12. 10.1016/j.pain.2011.10.031PubMedView Article
- Hughes DI, Sikander S, Kinnon CM, Boyle KA, Watanabe M, Callister RJ, Graham BA: Morphological, neurochemical and electrophysiological features of parvalbumin-expressing cells: a likely source of axo-axonic inputs in the mouse spinal dorsal horn. J Physiol 2012, 590: 3927–3951. 10.1113/jphysiol.2012.235655PubMed CentralPubMedView Article
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.