Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

Spinothalamic and propriospinal neurones in the upper cervical cord of the rat: terminations of primary afferent fibres on soma and primary dendrites

Summary Experiments were performed on rats to determine whether primary afferents from the upper cervical region terminate directly on Spinothalamic and propriospinal neurones. The central terminations of primary afferents from the upper cervical region were identified by diffusely filling their axons with horseradish peroxidase. Spinothalamic neurones or propriospinal neurones were identified in the same experimental animals by using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Approximately 3–11 % of Spinothalamic cells in laminae 4–6 of spinal segments C2–4 received apparent synaptic contacts from primary afferents on the soma or primary dendrites. Approximately 18–36% of propriospinal neurones with axons descending to lower thoracic or lumbar levels received apparent synaptic contacts on the soma or primary dendrites. These data provide anatomical evidence that Spinothalamic and long propriospinal neurones in the upper cervical cord are excited directly by primary afferents. The data also help to clarify the neural circuitry underlying somatic sensation and reflex movements evoked by neck receptors.     

The medullary relay from neck receptors to somatosensory thalamus in the rat: a neuroanatomical study

Summary Experiments were performed on rats to determine the location of thalamic projecting neurones in the medulla which receive direct contacts from neck primary afferents. The medullary terminations of primary afferents from the cervical region were identified by silver staining their degenerating terminals, diffusely filling their axons with horseradish peroxidase (HRP), or reacting for transganglionically transported HRP applied to muscle or cutaneous nerves. Neurones projecting to the ventrobasal thalamus were identified in the same experimental animals by using retrograde transport of HRP or Fluoro-Gold. En passant swellings or terminals of neck primary afferents were found in the vicinity of neurones projecting to the thalamus in the dorsolateral part of the rostral cuneate nucleus, the ventral aspect of the external cuneate nucleus, and the border zone between the two. Terminals of neck afferents and retrogradely labelled cells also coincided in nucleus x. Putative synaptic contacts were found in the region between the dorsolateral part of the rostral cuneate nucleus and ventromedial external cuneate nucleus. Cutaneous afferents from the neck were associated with thalamic projecting cells located along the dorsolateral border of the rostral cuneate nucleus, and afferents from neck muscles were associated with thalamic projecting cells in the caudal third of the external cuneate nucleus and in nucleus x.     

GABAergic boutons establish synaptic contacts with the soma and dendrites of cuneothalamic relay neurons in the rat cuneate nucleus

This study investigates the synaptic relation between -aminobutyric acid-immunoreactive (GABA-IR) and cuneothalamic relay neurons (CTNs) in the rat cuneate nucleus. Retrograde transport of wheat germ agglutinin conjugated with horseradish peroxidase complex (WGA-HRP) was used to label CTNs while anti-GABA immunogold serum was used for the detection of GABA-IR boutons associated with CTNs. With these procedures, immunogold-labelled GABA-IR boutons were found to form axosomatic, axodendritic and axospinous synapses with the WGA-HRP-labelled but immunonegative CTNs. Quantitative estimation showed that the mean ratios of GABA-IR to GABA-immunonegative boutons making synaptic contacts with somata, proximal dendrites, and distal dendrites were 47.9%, 49.1% and 34.7%, respectively. Statistical analysis showed that the incidence of GABA-IR boutons on the somata and proximal dendrites of CTNs was significantly higher than on the distal dendrites. Our results indicate that GABA is the primary inhibitory neurotransmitter in the cuneate nucleus, thereby emphasizing the importance of postsynaptic inhibition on cuneothalamic relay neurons.     

The subcortical generated somatosensory evoked potentials in non-cephalic,cephalic, and anterior neck referenced recordings in a patient with a cervico-medullary lesion: a clue to the identification of the P14/N14 and N13 generators

Summary Median nerve somatosensory evoked potentials (SEPs) were studied in a patient before and after the development of a cervico-medullary lesion. The first examination demonstrated normal subcortical generated potentials N13 and N14. The second examination, following a subarachnoid haemorrhage at the cervico-medullary junction, displayed a delayed and reduced amplitude P14/N14 peak on both sides. P14/N14 showed the same latency in all montages, using noncephalic, cephalic and anterior neck references. The N13 component was not significantly changed in latency compared with the first examination. The latencies of the N13 peak were variable in the different montages. They increased from the lower (C7) to the upper (C2) neck, whereas the latency of the N13 onset was identical in all montages. This alteration might be caused by a delayed near-field activity at C2 overlapping the N13 component. These results fit the hypothesis of two major generators responsible for subcortical SEPs; a near-field N13 component at the level of the lower neck and a far-field P14 component arising from the level of the cervico-medullary junction. An additional minor near-field activity generated by the cuneate nucleus is suspected.     

Cortical and subcortical plasticity in the brains of humans, primates, and rats after damage to sensory afferents in the dorsal columns of the spinal cord

The failure of injured axons to regenerate following spinal cord injury deprives brain neurons of their normal sources of activation. These injuries also result in the reorganization of affected areas of the central nervous system that is thought to drive both the ensuing recovery of function and the formation of maladaptive neuronal circuitry. Better understanding of the physiological consequences of novel synaptic connections produced by injury and the mechanisms that control their formation are important to the development of new successful strategies for the treatment of patients with spinal cord injuries. Here we discuss the anatomical, physiological and behavioral changes that take place in response to injury-induced plasticity after damage to the dorsal column pathway in rats and monkeys. Complete section of the dorsal columns of the spinal cord at a high cervical level in monkeys and rats interrupts the ascending axon branches of low threshold mechanoreceptor afferents subserving the forelimb and the rest of the lower body. Such lesions render the corresponding part of the somatotopic representation of primary somatosensory cortex totally unresponsive to tactile stimuli. There are also behavioral consequences of the sensory loss, including an impaired use of the hand/forelimb in manipulating small objects. In monkeys, if some of the afferents from the hand remain intact after dorsal column lesions, these remaining afferents extensively reactivate portions of somatosensory cortex formerly representing the hand. This functional reorganization develops over a postoperative period of 1 month, during which hand use rapidly improves. These recoveries appear to be mediated, at least in part, by the sprouting of preserved afferents within the cuneate nucleus of the dorsal column-trigeminal complex. In rats, such functional collateral sprouting has been promoted by the post-lesion digestion of the perineuronal net in the cuneate nucleus. Thus, this and other therapeutic strategies have the potential of enhancing sensorimotor recoveries after spinal cord injuries in humans.     

The differentiation of axonal and soma-dendritic spike activity

Summary Experiments were performed to examine the usefulness of mean spike duration measurements as a means of distinguishing between axonal and soma-dendritic activity recorded from the C.N.S. by glass insulated platinum microelectrodes. Units recorded from cat gracile and cuneate nuclei were separated into presynaptic and postsynaptic groups on the basis of: a) the maximum number of spikes evoked from a single electrical stimulus to the skin receptor area; b) the maximum frequency at which evoked spikes would follow every stimulus; c) the variability of latency at threshold stimulus intensity; d) the decrement of this variability upon increasing the intensity; e) the reduction of mean latency upon increasing stimulus intensity above threshold. Fifteen presynaptic units were recorded, all of which had short mean spike durations. Of the 41 postsynaptic units 5 exhibited short mean spike durations in the range associated with presynaptic units and were consequently classed as postsynaptic axons. The remaining postsynaptic units had long mean spike durations. On the basis of mean spike duration alone no presynaptic (i.e. primary afferent fibre) unit would have been erroneously classified as a postsynaptic (soma-dendritic) unit.     

Synaptophysin immunoreactivity and distributions of calcium-binding proteins highlight the functional organization of the rat's dorsal column nuclei

The mammalian dorsal column nuclei (DCN) are principally composed of the cuneate (CN) and gracile (GN) nuclei. Data presented here support previously published anatomical and functional evidence that the longitudinal organization of the CN and GN reflect the complex role of the DCN in somatosensory processing. The CN is organized longitudinally into three parts. Within the middle portion of this nucleus, primary afferent projections and cuneothalamic cells are concentrated. Although traditional cytoarchitectonic analyses had failed to detect this tripartite organization in rats, we found evidence for it, with a functional middle region, extending approximately 0.2–0.9 mm caudal to the obex, characterized by precise somatotopy of primary afferent terminations and corresponding somatotopy of cytochrome oxidase (CO) blotches. Additional evidence is presented here consistent with a functionally distinct middle region within the rat's CN: (1) patches of dense synaptophysin (a synaptic-vesical-associated protein)-immunoreactivity (SYN-IR) are limited to the middle CN region, coincident with the dense CO blotches; (2) neurons immunoreactive for the calcium-binding proteins calbindin-D₂₈ (CB), calretinin (CR) and parvalbumin (PV) are concentrated in the middle CN region. Furthermore, in adult rats subjected to perinatal forepaw removal, (1) the patterns of SYN-IR in the middle region of the CN are disrupted, as had previously been shown for the patterns of CO blotches; (2) in contrast, however, distributions of CN cells with PV-, CB- and CR-IR are unaffected. Evidence for a tripartite division in the GN is also presented, based on the distributions of cells with PV-, CB- and CR-IR.     

Neurons in the dorsal column nuclei of the rat emit a moderate projection to the ipsilateral ventrobasal thalamus

The dorsal column nuclei (DCN; gracile and cuneate nuclei) give rise to the medial lemniscus, the fibre system that provides an organised somatosensory input to the thalamus. Unlike the spinothalamic and trigeminothalamic tracts that project, also to the ipsilateral thalamus, the medial lemniscus system is believed to be entirely crossed. We demonstrate that DCN emit a small number of axons that reach the ipsilateral thalamus. As retrograde fluorescent neuronal tracer Fluoro-gold was stereotaxically injected in the ventrobasal thalamus of nine young adult Wistar rats. The injection foci were voluminous and encroached upon adjacent nuclei, but the periphery of the injection halo never spilled over to the contralateral thalamus. All sections of the contralateral gracile and cuneate nuclei and the midline nucleus of Bischoff contained abundant retrogradely labelled neurons. The comparison with the Nissl-stained parallel sections suggests that approximately 70–80% of the DCN neurons project to the contralateral thalamus. Counting of retrogradely labelled neurons in two cases revealed 4,809 and 4,222 neurons in the contralateral and 265 and 214 in the ipsilateral DCN, respectively. Thus, although less prominent than the ipsilateral spinothalamic tract, the lemniscal system also emits an ipsilateral projection that accounts for about 5% of the neuronal population in DCN that innervates the ventrobasal thalamus.     

Aβ-fiber intensity stimulation of chronically constricted median nerve induces c-fos expression in thalamic projection neurons of the cuneate nucleus in rats with behavioral signs of neuropathic pain

This study was aimed to investigate the possible involvement of neurons in the cuneate nucleus (CN) in the processing of Aβ afferent inputs evoked by electrical stimulation of constricted median nerve in rats with behavioral signs of neuropathic pain. Immunohistochemical localization of Fos protein was used to examine the neuronal activation, and the combination of Fos immunohistochemistry with the retrograde labeling of Fluoro-Gold (FG) injected into the ventrobasal complex of the thalamus was used to characterize the activated neurons. Two weeks after unilateral median nerve constriction injury, the rats exhibited behavioral signs of neuropathic pain in the affected forepaws. In rats after nerve injury but without electrical stimulation, some Fos-like immunoreactive (Fos-LI) neurons were detected in the dorsal horn of the seventh cervical segment (C7) but none was found in the CN. Similar features were also noted when the stimulation of the intact median nerve served as an additional control. After Aβ-fiber intensity stimulation of the previously constricted median nerve, an increase in number of Fos-LI neurons occurred in the medial half of the ipsilateral C7 dorsal horn as well as in the ipsilateral CN. In the latter, the Fos-LI neurons were located in the median nerve projection territory throughout the nucleus. Most of the Fos-LI neurons were distributed in the middle region of the CN, with about 78% of them emitting FG fluorescence indicating that they were cuneothalamic projection neurons. The results of this study suggest that the dorsal column-medial lemniscal system may contribute to the transmission and modulation of Aβ-fiber mediated neuropathic pain signals.