Neurons In Dorsal Column Nuclei Research Articles

Temporal Patterns of Individual Neuronal Firing in Rat Dorsal Column Nuclei Provide Information Required for Somatosensory Discrimination.

A wealth of mechanical information from the body generates various forms of sensory experience during touch or kinesthesia. Dorsal column nuclei (DCN) in the medulla are the first relay station for somatosensory inputs from peripheral receptors. These nuclei integrate somatosensory information and send the output to higher-order centers; therefore, investigating the firing patterns of DCN neurons should elucidate coding principles within the somatosensory system. In this study, we quantified the firing patterns of DCN neurons and examined whether the firing patterns of particular neurons are altered when moving tactile stimuli are applied in different directions. The activities of 17 neurons in the DCN of anesthetized rats were selected and their firing patterns were analyzed using LvR, which refers to the local variation of intervals of action potentials (i.e., the cross-correlation between consecutive intervals of action potentials) compensated by the refractoriness constant, R. The LvR of the 17 neurons ranged widely from 0.35 to 2.28. Of the 17 neurons, 12 responded to hair deflection (hair neurons), whereas five responded specifically to movement of forelimb joints. In 11 of 12 hair neurons, moving stimuli were applied in two to four different directions, which yielded 25 pairs of comparisons. Of these, 14 pairs (56%) showed significant differences in LvR. Among these 14 pairs, the range of LvR fluctuation was 0.13 ± 0.06 (mean ± standard deviation) and its effect size (Cohen's d) was 0.6 ± 0.2. These results suggest that the firing pattern of individual DCN neurons may contribute to somatosensory discrimination.

Reorganization of sensory pathways after neonatal hemidecortication in rats

We investigated ascending somatosensory pathways in neonatally hemidecorticated rats. Injection of an anterograde tracer, biotinylated dextran amine (BDA), into the contralesional dorsal root ganglions revealed ipsilateral projections to the dorsal column nuclei (DCN) in hemidecorticated rats as well as in normal rats. Injection of BDA into the DCN on the same side revealed that while most axons projected to the contralateral thalamus, some axons were detected in the ipsilateral thalamus in hemidecorticated rats while such projections were rarely detected in normal rats. The results suggest that aberrant ipsilateral projections of DCN neurons contralateral to the lesion developed after the hemidecortication.

Effect of movement on SEPs generated by dorsal column nuclei

To investigate the effect of the voluntary movement on the amplitude of the somatosensory evoked potentials (SEPs) recorded by an epidural electrode at level of the dorsal column nuclei (DCN). Five patients, suffering from chronic pain resistant to pharmacological treatment, underwent an epidural electrode implant at high cervical spinal cord level (C2) for neuromodulation. After tibial nerve stimulation, SEPs were recorded from the epidural electrode contacts, from a Cz lead, and from two electrodes placed over the 12th dorsal vertebra and 4th lumbar vertebra, respectively. SEPs were recorded at rest and during a voluntary flexo-extension movement of the stimulated foot. Beyond the low-frequency SEPs, also the high-frequency oscillations (HFOs), obtained by filtering the recorded traces by means of a 1000-2000 Hz bandpass offline, were analysed. The epidural electrode contacts recorded a triphasic potential (P1-N1-P2), whose negative peak showed a latency similar to that of the P30 far-field response obtained from the scalp. The epidural potential amplitude was significantly decreased by the voluntary movement, as compared to the rest (p<0.01). A main HFO peak, identifiable at around 1200 Hz, was significantly lower in amplitude during movement than at rest (p=0.008). Our findings suggest that the epidural C2 triphasic wave is a potential arising from DCN. The low-frequency epidural SEP component is subtended by a 1200 Hz HFO, probably generated by post-synaptic events. The amplitude reduction of the DCN response during movement is possibly due to decreased excitability of the DCN neurons receiving the somatosensory ascending input.

Modulation of neuronal activity in dorsal column nuclei by upper cervical spinal cord stimulation in rats

Clinical human and animal studies show that upper cervical spinal cord stimulation (cSCS) has beneficial effects in treatment of some cerebral disorders, including those due to deficient cerebral circulation. However, the underlying mechanisms and neural pathways activated by cSCS using clinical parameters remain unclear. We have shown that a cSCS-induced increase in cerebral blood flow is mediated via rostral spinal dorsal column fibers implying that the dorsal column nuclei (DCN) are involved. The aim of this study was to examine how cSCS modulated neuronal activity of DCN. A spring-loaded unipolar ball electrode was placed on the left dorsal column at cervical (C2) spinal cord in pentobarbital anesthetized, ventilated and paralyzed male rats. Stimulation with frequencies of 1, 10, 20, 50 Hz (0.2 ms, 10 s) and an intensity of 90% of motor threshold was applied. Extracellular potentials of single neurons in DCN were recorded and examined for effects of cSCS. In total, 109 neurons in DCN were isolated and tested for effects of cSCS. Out of these, 56 neurons were recorded from the cuneate nucleus and 53 from the gracile nucleus. Mechanical somatic stimuli altered activity of 87/109 (83.2%) examined neurons. Of the neurons receiving somatic input, 62 were classified as low-threshold and 25 as wide dynamic range. The cSCS at 1 Hz changed the activity of 96/109 (88.1%) of the neurons. Neuronal responses to cSCS exhibited multiple patterns of excitation and/or inhibition: excitation (E, n=21), inhibition (I, n=19), E–I ( n=37), I–E ( n=8) and E–I–E ( n=11). Furthermore, cSCS with high-frequency (50 Hz) altered the activity of 92.7% (51/55) of tested neurons, including 30 E, 24 I, and 2 I–E responses to cSCS. These data suggested that cSCS significantly modulates neuronal activity in DCN. These nuclei might serve as a neural relay for cSCS-induced effects on cerebral dysfunction and diseases.

Cortical influences on rapid brainstem plasticity

Cortical contributions to brainstem plasticity in the somatosensory system are poorly understood. Tactile receptive fields (RFs) of brainstem dorsal column nuclei (DCN) neurons rapidly enlarge when peripheral inputs are disrupted by local anesthetic blocks with lidocaine (LID). Cortical inputs appear to influence this plasticity because enlargements have been shown to be greater when cortical inputs are disrupted. Like disruptions of peripheral inputs, disruptions of DCN inhibition by DCN administration of the GABAA receptor antagonist bicuculline methiodide (BMI) also cause rapid enlargements of DCN RFs when cortical inputs are intact. These findings leave questions about interactions between cortical inputs, DCN inhibition, and DCN RF plasticity. To study potential interactions, the present experiments evaluated RF sizes of DCN tactilely responsive neurons in anesthetized rats following DCN microinjection of BMI when cortical inputs were acutely disrupted or intact. These tests were also supplemented by subsequent LID tests to directly compare post-BMI and post-LID effects on the same RF. BMI caused DCN RF enlargements when cortical inputs were disrupted or intact; however, enlargements after cortical input disruption were greater than when cortical inputs were intact. Following RF enlargement and retraction after BMI, LID often caused a second enlargement of the same RF, across skin that partially matched skin involved in the enlargement after BMI. This occurred when cortical inputs were disrupted or intact. We hypothesize that cortical inputs are not required for BMI and LID to initiate partially matching enlargements in individual DCN tactile RFs, however, cortical inputs constrain magnitudes of these enlargements.

Involvement of Dorsal Column Nucleus Neurons in Nociceptive Transmission in Aged Rats

To clarify the functional role of the dorsal column nucleus (DCN) in nociception in rats with advancing age, single neuronal activity and substance P-like immunoreactivity (SP-LI) of the gracile nucleus (GN) were studied in aged rats (29 to 34 mo old) and adult rats (9 to 12 mo old). A total of 122 neurons [aged: 34 wide-dynamic-range (WDR), two nociceptive-specific (NS), and 32 low-threshold mechanical (LTM) neurons; adult: 22 WDR and 32 LTM neurons] were recorded from GN. For WDR neurons, the latency to antidromic activation of the ventral posterior lateral nucleus of the thalamus showed no difference between the aged and adult rats. Sciatic nerve stimulation with C-fiber intensity induced responses of GN with significantly longer latency in aged rats than in adults, whereas there was no difference in the response latency to A-fiber intensity stimulation. Background activity and afterdischarges were significantly higher in the aged rats than those in the adult rats. Responses to noxious mechanical and thermal stimuli were significantly greater in the aged rats during application of graded stimuli. There were no significant differences in responses to nonnoxious mechanical stimulus, mechanical response threshold, and the size of the receptive fields between neurons in the aged and adult rats. The area occupied by SP-LI fibers in the GN and the size of SP-LI dorsal root ganglia neurons were significantly larger in aged rats than in adults. The present findings suggest that the hyperexcitability of GN neurons could be involved in abnormal noxious pain sensations with advancing age.

Processing of Vibrotactile Inputs From Hairy Skin by Neurons of the Dorsal Column Nuclei in the Cat

The capacity of single neurons of the dorsal column nuclei (DCN) for coding vibrotactile information from the hairy skin has been investigated in anesthetized cats to permit quantitative comparison first with the capacities of DCN neurons responding to glabrous skin vibrotactile inputs and second with those of spinocervical tract neurons responding to vibrotactile inputs from hairy skin. Dynamically sensitive tactile neurons of the DCN the input of which came from hairy skin could be divided into two classes, one associated with hair follicle afferent (HFA) input, the other with Pacinian corpuscle (PC) input. The HFA-related class was most sensitive to low-frequency (<50 Hz) vibration and had a graded response output as a function of vibrotactile intensity changes. PC-related neurons had a broader vibrotactile sensitivity, extending to > or =300 Hz and appeared to derive their input from the margins of hairy skin, near the footpads, or from deeper PC sources such as the interosseous membranes or joints. HFA-related neurons had phaselocked responses to vibration frequencies up to approximately 75 Hz, whereas PC neurons retained this capacity up to frequencies of approximately 300 Hz with tightest phaselocking between 50 and 200 Hz. Quantitative measures of phaselocking revealed that the HFA-related neurons provide the better signal of vibrotactile frequency up to approximately 50 Hz with a switch-over to the PC-related neurons above that value. In conclusion, the functional capacities of these two classes of cuneate neuron appear to account for behavioral vibrotactile frequency discriminative performance in hairy skin, in contrast to the limited capacities of vibrotactile-sensitive neurons within the spinocervical tract system.

Localization and function of the Kv3.1b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii.

The voltage-gated potassium channel subunit Kv3.1 confers fast firing characteristics to neurones. Kv3.1b subunit immunoreactivity (Kv3.1b-IR) was widespread throughout the medulla oblongata, with labelled neurones in the gracile, cuneate and spinal trigeminal nuclei. In the nucleus of the solitary tract (NTS), Kv3.1b-IR neurones were predominantly located close to the tractus solitarius (TS) and could be GABAergic or glutamatergic. Ultrastructurally, Kv3.1b-IR was detected in NTS terminals, some of which were vagal afferents. Whole-cell current-clamp recordings from neurones near the TS revealed electrophysiological characteristics consistent with the presence of Kv3.1b subunits: short duration action potentials (4.2 +/- 1.4 ms) and high firing frequencies (68.9 +/- 5.3 Hz), both sensitive to application of TEA (0.5 mm) and 4-aminopyridine (4-AP; 30 mum). Intracellular dialysis of an anti-Kv3.1b antibody mimicked and occluded the effects of TEA and 4-AP in NTS and dorsal column nuclei neurones, but not in dorsal vagal nucleus or cerebellar Purkinje cells (which express other Kv3 subunits, but not Kv3.1b). Voltage-clamp recordings from outside-out patches from NTS neurones revealed an outward K(+) current with the basic characteristics of that carried by Kv3 channels. In NTS neurones, electrical stimulation of the TS evoked EPSPs and IPSPs, and TEA and 4-AP increased the average amplitude and decreased the paired pulse ratio, consistent with a presynaptic site of action. Synaptic inputs evoked by stimulation of a region lacking Kv3.1b-IR neurones were not affected, correlating the presence of Kv3.1b in the TS with the pharmacological effects.

Neuronal mechanisms mediating the variability of somatosensory evoked potentials during sleep oscillations in cats

The slow oscillation (SO) generated within the corticothalamic system is composed of active and silent states. The studies of response variability during active versus silent network states within thalamocortical system of human and animals provided inconsistent results. To investigate this inconsistency, we used electrophysiological recordings from the main structures of the somatosensory system in anaesthetized cats. Stimulation of the median nerve (MN) elicited cortical responses during all phases of SO. Cortical responses to stimulation of the medial lemniscus (ML) were virtually absent during silent periods. At the ventral-posterior lateral (VPL) level, ML stimuli elicited either EPSPs in isolation or EPSPs crowned by spikes, as a function of membrane potential. Response to MN stimuli elicited compound synaptic responses and spiked at any physiological level of membrane potential. The responses of dorsal column nuclei neurones to MN stimuli were of similar latency, but the latencies of antidromic responses to ML stimuli were variable. Thus, the variable conductance velocity of ascending prethalamic axons was the most likely cause of the barrages of synaptic events in VPL neurones mediating their firing at different level of the membrane potential. We conclude that the preserved ability of the somatosensory system to transmit the peripheral stimuli to the cerebral cortex during all the phases of sleep slow oscillation is based on the functional properties of the medial lemniscus and on the intrinsic properties of the thalamocortical cells. However the reduced firing ability of the cortical neurones during the silent state may contribute to impair sensory processing during sleep.

Nociceptive stimuli induce changes in somatosensory responses of rat dorsal column nuclei neurons

Accumulating evidence suggest that the dorsal column nuclei (DCN) neurons play a role in nociception. To evaluate DCN neuronal responses to nociceptive stimuli, unit recordings were performed in urethane-anesthesized rats. Neurons selected for this analysis displayed a low spontaneous firing rate and some of them were antidromically activated by electrical stimulation of the ventral posterolateral thalamic nucleus. Formalin injections into receptive fields (RFs) of DCN cells, or applications of short-lasting and long-lasting thermal nociceptive stimuli were used. DCN neurons displayed smaller responses when long-lasting nociceptive thermal stimuli were applied to their RFs in comparison with values obtained from the innocuous cutaneous stimulation (5.2±1.0 and 4.0±0.6 spikes/stimuli, respectively; p=0.02). Formalin also decreased the responses to innocuous cutaneous stimuli when these stimuli were applied to the formalin injection site (2.6±0.3 spikes/stimuli in control conditions and 1.8±0.3 spikes/stimuli 20 min after formalin; p=0.002). In contrast, responses to sensory stimuli applied at the periphery of the RF after formalin injection increased (2.2±0.2 to 2.8±0.3 spikes/stimuli; p=0.005). In some cases, DCN neurons expanded their RF. Fiber input to the DCN did not modify their somatosensory responses when nociceptive stimuli were applied. Results demonstrate that thermal and formalin nociceptive stimuli modify the somatosensory responses of DCN neurons. Thus, decreasing somatosensory responses at the pain induction site or the generation of allodynia may be due to the activity of DCN neurons.

Intrinsic spontaneous activity and subthreshold oscillations in neurones of the rat dorsal column nuclei in culture

The basis of rhythmic activity observed at the dorsal column nuclei (DCN) is still open to debate. This study has investigated the electrophysiological properties of isolated DCN neurones deprived of any synaptic influence, using the perforated-patch technique. About half of the DCN neurones (64/130) were spontaneously active. More than half of the spontaneous neurones (36/64) showed a low threshold membrane oscillation (LTO) with a mean frequency of 11.4 Hz (range: 4.3–22.1 Hz, n= 20; I= 0). Cells showing LTOs also invariably showed a rhythmic 1.2 Hz clustering activity (groups of 2–5 action potentials separated by silent LTO periods). Also, more than one-third of the silent neurones presented clustering activity, always accompanied by LTOs, when slightly depolarised. The frequency of LTOs was voltage dependent and could be abolished by TTX (0.5 μM) and riluzole (30 μM), suggesting the participation of a sodium current. LTOs were also abolished by TEA (15 mM), which transformed clustering into tonic activity. In voltage clamp, most DCN neurones (85 %) showed a TTX-/riluzole-sensitive persistent sodium current (INa,p), which activated at about -60 mV and had a half-maximum activation at −49.8 mV. An M-like, non-inactivating outward current was present in 95 % of DCN neurones, and TEA (15 mM) inhibited this current by 73.7 %. The non-inactivating outward current was also inhibited by barium (1 mM) and linopirdine (10 μM), which suggests its M-like nature; both drugs failed to block the LTOs, but induced a reduction in their frequency by 56 and 20 %, respectively. These results demonstrate for the first time that DCN neurones have a complex and intrinsically driven clustering discharge pattern, accompanied by subthreshold membrane oscillations. Subthreshold oscillations rely on the interplay of a persistent sodium current and a non-inactivating TEA-sensitive outward current.

Intrinsic spontaneous activity and subthreshold oscillations in neurones of the rat dorsal column nuclei in culture.

The basis of rhythmic activity observed at the dorsal column nuclei (DCN) is still open to debate. This study has investigated the electrophysiological properties of isolated DCN neurones deprived of any synaptic influence, using the perforated-patch technique. About half of the DCN neurones (64/130) were spontaneously active. More than half of the spontaneous neurones (36/64) showed a low threshold membrane oscillation (LTO) with a mean frequency of 11.4 Hz (range: 4.3-22.1 Hz, n = 20; I = 0). Cells showing LTOs also invariably showed a rhythmic 1.2 Hz clustering activity (groups of 2-5 action potentials separated by silent LTO periods). Also, more than one-third of the silent neurones presented clustering activity, always accompanied by LTOs, when slightly depolarised. The frequency of LTOs was voltage dependent and could be abolished by TTX (0.5 microM) and riluzole (30 microM), suggesting the participation of a sodium current. LTOs were also abolished by TEA (15 mM), which transformed clustering into tonic activity. In voltage clamp, most DCN neurones (85%) showed a TTX-/riluzole-sensitive persistent sodium current (INa,p), which activated at about -60 mV and had a half-maximum activation at -49.8 mV. An M-like, non-inactivating outward current was present in 95% of DCN neurones, and TEA (15 mM) inhibited this current by 73.7 %. The non-inactivating outward current was also inhibited by barium (1 mM) and linopirdine (10 microM), which suggests its M-like nature; both drugs failed to block the LTOs, but induced a reduction in their frequency by 56 and 20%, respectively. These results demonstrate for the first time that DCN neurones have a complex and intrinsically driven clustering discharge pattern, accompanied by subthreshold membrane oscillations. Subthreshold oscillations rely on the interplay of a persistent sodium current and a non-inactivating TEA-sensitive outward current.

Quantitative stereological evaluation of the gracile and cuneate nuclei and their projection neurons in the rat.

Stereological methods were employed to estimate the volume and neuron numbers of the rat dorsal column nuclei (DCN). These methods were applied to Nissl-stained sections from control animals and cases that received injections of horseradish peroxidase in the thalamus, the cerebellum, or the spinal cord. Additional cases received combinations of fluorescent tracers in the same structures, to examine whether some of the retrogradely labeled neurons sent collaterals to different targets. The mean volume of the DCN is 0.81 mm(3) (range 0.65-1.10 mm(3)), of which 3%, 39%, and 59% correspond, respectively, to the nucleus of Bischoff (Bi), the gracile (Gr), and the cuneate (Cu) nuclei. Within Cu, the middle division (CuM) is the largest (42%), followed by the rostral (CuR; 36%) and caudal (CuC; 22%) divisions. The mean total number of neurons in the DCN is 16,000 (range 12,400-19,500), of which 2.4%, 34.0% and 63.6% correspond, respectively, to Bi, Gr, and Cu. Within Cu, CuM contains 48% of all neurons, and 27% correspond to CuR and 25% to CuC. Interanimal variability is moderate for the whole DCN and Cu but increases when individual nuclei are considered. About 80% of DCN neurons project to the thalamus, 3% to the spinal cord, and 7% to the cerebellum. Thalamic-projecting cells are more numerous in CuM and Gr (83%), and relatively less common in Bi and CuC (72-74%). Most of the DCN neurons projecting to the spinal cord appear in CuC and CuM. Two-thirds of the neurons projecting to the cerebellum are located in CuR, 20% in CuM, and 15% in Gr. A small fraction of neurons projects simultaneously to spinal cord and thalamus.

Insulin-like growth factor I modifies electrophysiological properties of rat brain stem neurons.

On systemic injection, insulin-like growth factor I (IGF-I) elicits a prolonged increase in the excitability of dorsal column nuclei (DCN) cells in the brain stem as well as other target neurons within the brain. We have explored the cellular mechanisms involved in the stimulatory effects of IGF-I as well as its functional consequences. In a rat slice preparation, IGF-I induced a sustained depolarization of 2-5 mV in 81% of DCN neurons. Depolarization was accompanied with an increase in the input resistance (15%). Voltage-clamp recordings displayed that IGF-I decreased a K+-mediated A current (60%). Furthermore, IGF-I increased, in 78% of cells, the peak amplitude (25%), and rising slope (32%) of the excitatory postsynaptic potential evoked by dorsal column stimulation; in this case, a presynaptic facilitatory process appears to be involved. When anesthetized adult rats are injected in the carotid artery with IGF-I, extracellularly recorded propioceptive DCN neurons not only show increased spike activity but also an expansion of their cutaneous receptive field in 83% of DCN cells. Significantly, the increased excitability evoked by IGF-I in the DCN cells depends both in vivo and in vitro, on activation of p38 mitogen-activated protein kinase (MAPK), a Ser-kinase known to modulate K+ channel activity. We concluded that systemic IGF-I modulated the electrophysiological properties of target neurons within the brain. In turn, these changes probably contribute to functional reorganization processes such as expansion of neuronal receptive fields.

Midbrain projecting dorsal column nucleus neurons in a reptile

The origin of midbrain projecting cells in the dorsal column nucleus (DCN) was investigated in reptiles, Caiman crocodilus, using a retrograde tracer. Labeled neurons were confined to a caudal–central portion of the DCN. Midbrain projecting DCN neurons had round, oval, or triangular soma and were small. While neurons that project to the spinal cord in Caiman are also located in the caudal half of the DCN, midbrain projecting cells are located more dorsally and are smaller than those whose axons terminate in the spinal cord. Taken together, these observations suggest that the DCN in Caiman is subdivided, at least in part, according to target location. In view of similar findings in certain birds and mammals, subdivisions of the DCN into sectors is likely a phylogenetically ancient feature of amniote sensory systems transmitting somatosensory information from the body surface.

Stimulation in the rat fastigial nucleus enhances the responses of neurons in the dorsal column nuclei to innocuous stimuli

The cerebellum was recently proposed to play a role in cognition and sensation in addition to motor phenomena. We have shown that the cerebellum is involved in the processing of sensory nociceptive information. In this study, the activity of neurons in the dorsal column nuclei (DCN) was tested following stimulation in the rat fastigial nucleus. The results showed an enhancement of the extracellularly recorded responses of DCN neurons to somatic non-noxious stimuli following injection of d,l-homocysteic acid (0.1 M, 1 μl) into the area of the fastigial nucleus. We conclude that the cerebellum influences the processing of non-noxious somatosensory information at the level of the DCN, an important relay and a center for the processing of fine tactile and vibratory information. This observation is not yet supported by clinical data.

Nerve injury-induced changes in opioid modulation of wide dynamic range dorsal column nuclei neurones

In the present study we investigated the effects of spinal morphine on the electrically and naturally evoked responses of gracile nuclei neurones in a rat model of neuropathy, induced by the tight ligation of lumbar L5/6 spinal nerves. Two weeks after surgery, animals were prepared for electrophysiological recordings and neuronal responses were characterised to a range of controlled natural (brush, low- and high-intensity von Frey filaments, heat 45°C) and peripheral electrical stimuli. Morphine (0.1, 0.25, 1 and 5 μg) was applied spinally and its effect was compared to that in sham-operated or naive animals. Following surgery, all neuropathic rats exhibited signs of mechanical allodynia. Nerve injury induced a significant increase in the receptive field size of gracile nuclei neurones, and also produced a non-significant increase in the proportion and level of spontaneous activity in these neurones. The baseline electrical and natural evoked responses remained unaltered. Spinal morphine reduced both the Aδ-fibre- and C-fibre-evoked responses of gracile nuclei neurones, and similarly inhibited the heat-evoked responses of neuropathic, sham-operated and naive rats. Morphine, however, produced only minor reductions (<30% inhibition of pre-drug control responses) of the Aβ-fibre- and brush-evoked responses of gracile nuclei neurones. These drug effects were similar in all animal groups. In complete contrast, morphine produced a marked inhibition of the low-intensity punctate mechanical evoked responses (von Freys 2 and 9 g) after nerve injury, an effect that was totally lacking in the sham-operated or naive animal groups. This dramatic shift was selective for the low-intensity punctate mechanical stimuli and such an effect was not seen with the noxious mechanical punctate stimulus (von Frey 75 g) where there was a modest inhibition in all groups. Our results suggest that there is plasticity in the opioid modulation of dorsal column projection pathways following spinal nerve ligation and these alterations appear to interact with sensory pathways conveying low-threshold punctate stimuli.

Inflammatory pain reduces correlated activity in the dorsal column nuclei

Persistent pain can result in sensitization of neurons in the spinal cord dorsal horn and produce physiological changes in sites such as the thalamus, that receive projections from the dorsal horn. Although the dorsal column nuclei receive both primary afferent input and projections from the dorsal horn, their participation in persistent pain states is relatively unexplored, perhaps because they play a limited role in acute, cutaneous nociception. We have used a model of inflammatory pain to examine the physiological properties of dorsal column nucleus neurons during persistent pain. We used this model in order to minimize direct damage to large myelinated primary afferents that project directly to the dorsal column nuclei. Inflammation was produced by injection of complete Freund’s adjuvant into one hindpaw in rats, and neurons in the gracile nucleus were recorded 2–8 days later. Inflammation resulted in increased responsiveness to nociceptive (pinch) stimulation and increased incidence of afterdischarge firing 2–3 days after injection. Spontaneous activity was increased 6–8 days after injection. Inflammation decreased the strength of correlated firing in neuron pairs that shared common inputs, but did not affect the strength of monosynaptic interactions between neurons. These results suggest that the dorsal column nuclei can participate in persistent pain processes. Based on their anatomical connections, the dorsal column nuclei may contribute to thalamic changes during persistent pain as well as to supraspinal centers that modulate pain transmission in the spinal cord.

Rhythmic neuronal interactions and synchronization in the rat dorsal column nuclei

Single-unit and multiunit activities were recorded from dorsal column nuclei of anesthetized rats in order to study the characteristics of the oscillatory activity expressed by these cells and their neuronal interactions. On the basis of their firing rate characteristics in spontaneous conditions, two types of dorsal column nuclei cell have been identified. Low-frequency cells (74%) were silent or displayed a low firing rate (1.9±0.48 spikes/s), and were identified as thalamic-projecting neurons because they were activated antidromically by medial lemniscus stimulation. High-frequency cells (26%) were characterized by higher discharge rates (27.2±5.1 spikes/s). None of them was antidromically activated by medial lemniscus stimulation. Low-frequency neurons showed a non-rhythmic discharge pattern spontaneously which became rhythmic under sensory stimulation of their receptive fields (48% of cases; 4.8±0.23 Hz). All high-frequency neurons showed a rhythmic discharge pattern at 13.8± 0.68 Hz either spontaneously or during sensory stimulation of their receptive fields. The shift predictor analysis indicated that oscillatory activity is not phase-locked to the stimulus onset in either type of cell, although the stimulus can reset the phase of the rhythmic activity of high-frequency cells. Cross-correlograms between pairs of low-frequency neurons typically revealed synchronized rhythmic activity when the overlapping receptive fields were stimulated. Rhythmic synchronization of high-frequency discharges was rarely observed spontaneously or under sensory stimulation. High-frequency neuronal firing could be correlated with the low-frequency neuronal activity or more often with the multiunit activity during sensory stimulation. Moreover, the presence of oscillatory activity modulated the sensory responses of dorsal column nuclei cells, favoring their responses. These findings indicate that thalamic-projecting and non-projecting neurons in dorsal column nuclei exhibited distinct oscillatory characteristics. However, both types of neuron may be entrained into an oscillatory rhythmic pattern when their overlapping receptive fields are stimulated, suggesting that in those conditions the dorsal column nuclei generate a populational oscillatory output to the somatosensory thalamus which could modulate and amplify the effectiveness of the somatosensory transmission.

Dorsal column nuclei neurons recorded in a brain stem-spinal cord preparation: characteristics and their responses to dorsal root stimulation.

Recordings were obtained from dorsal column nucleus (DCN) neurons in a neonatal rat brain stem-spinal cord preparation to study their basic electrophysiological properties and responses to stimulation of a dorsal root. Whole-cell patch-clamp recordings were made from 21 neurons that responded to dorsal root stimulation with a fast excitatory postsynaptic potential (EPSP). These neurons were located lateral to, but at the level of, the area postrema at depths of 100-268 microm below the dorsal surface of the brain. The neurons could be divided into groups according to the shape of their action potentials or voltage responses to hyperpolarizing current steps; however, the response profiles of the groups of neurons to dorsal root stimulation were not significantly different and all neurons were considered together. Dorsal root stimulation elicited excitatory postsynaptic potentials (EPSPs) in all neurons with a very low variability in onset latency and an ability to follow 100-Hz stimulation, indicating that they were mediated by activation of a monosynaptic pathway. The peak amplitude of the EPSP increased with membrane hyperpolarization, and applications of the non-NMDA receptor antagonists 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2, 3-dione (NBQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) decreased the amplitude of the EPSP to 14.2% of the control response (n = 6). The descending phase of the EPSP decreased with membrane hyperpolarization and was reduced by the N-methyl-D-aspartate (NMDA) receptor antagonist AP-5 (n = 2). The EPSPs were also reduced in amplitude by applications of the gamma-aminobutyric acid-B (GABA(B)) receptor agonist baclofen, which had no effect on membrane potential or input resistance. These results show that fast EPSPs in DCN neurons elicited by dorsal root stimulation are mediated by an excitatory amino acid acting at both non-NMDA and, to a lesser extent, NMDA receptors. In addition, GABA acting at presynaptic GABA(B) receptors can inhibit these responses.