Antonio Canedo

Spatial and cortical influences exerted on cuneothalamic and thalamocortical neurons of the cat

This work aimed to study the responses of cuneothalamic and thalamocortical cells to electrical stimulation of the body surface in α‐chloralose‐anaesthetized cats. It was found that both classes of cells had a central excitatory receptive field, an edge overlapping the field centre whose stimulation elicited inhibitory–excitatory (cuneothalamic cells) and excitatory–inhibitory (thalamocortical cells) sequences, and a surrounding or peripheral area usually being inhibitory. Manipulating the descending corticofugal activity by removing the fronto‐parietal cortex, electrical stimulation, or by placing picrotoxin or muscimol over the sensorimotor cortex demonstrated that the cortical feedback potentiated effects driven from the field centre and the surround. In particular this potentiated centre‐driven excitation and surround‐driven inhibition, but some of the data points to more complex patterns. The inhibition elicited in cuneothalamic cells from the edge and the surround of the field was faster than the excitation induced from the field centre. Effects at the edge of the field centre included late excitatory responses relayed via the cerebral cortex. There were also direct corticofugal excitatory inputs to the field centre. Excitatory surrounds were occasionally observed, the assumption being that in most cases these were suppressed by the enhanced inhibition driven from the cortex. The data indicate that the cortico‐subcortical feedback contributes not only to enhance the surround antagonism of a centre response but also to increase the time resolution of thalamic and cuneate relay somesthetic neurons.

Lemniscal recurrent and transcortical influences on cuneate neurons

Intracellular recordings were obtained from cuneate neurons of chloralose-anesthetized, paralysed cats to study the synaptic responses induced by electrical stimulation of the contralateral medial lemniscus. From a total of 178 cells sampled, 109 were antidromically fired from the medial lemniscus, 82 of which showed spontaneous bursting activity. In contrast, the great majority (58/69) of the non-lemniscal neurons presented spontaneous single spike activity. Medial lemniscus stimulation induced recurrent excitation and inhibition on cuneolemniscal and non-lemniscal cells. Some non-lemniscal neurons were activated by somatosensory cortex and inhibited by motor cortex stimulation. Some other non-lemniscal cells that did not respond to medial lemniscus stimulation in control conditions were transcortically affected by stimulating the medial lemniscus after inducing paroxysmal activity in the sensorimotor cortex. These findings indicate that different sites in the sensorimotor cortex can differentially influence the sensory transmission through the cuneate, and that the distinct available corticocuneate routes are selected within the cerebral cortex. From a total of 92 cells tested, the initial effect induced by low-frequency stimulation of the sensorimotor cortex was inhibition on most of the cuneolemniscal neurons (32/52) and excitation on the majority of the non-lemniscal cells (25/40). The fact that a substantial proportion of cuneolemniscal and non-lemniscal cells was excited and inhibited, respectively, suggests that the cerebral cortex may potentiate certain inputs by exciting and disinhibiting selected groups of cuneolemniscal cells. Finally, evidence is presented demonstrating that the tendency of the cuneolemniscal neurons to fire in high-frequency spike bursts is due to different mechanisms, including excitatory synaptic potentials, recurrent activation through lemniscal axonal collaterals, and via the lemnisco-thalamo-cortico-cuneate loop.A corticocuneate network circuit to explain the results is proposed.

The lemniscal–cuneate recurrent excitation is suppressed by strychnine and enhanced by GABAA antagonists in the anaesthetized cat

In the somatosensory system, cuneolemniscal (CL) cells fire high frequency doublets of spikes facilitating the transmission of sensory information to diencephalic target cells. We studied how lemniscal feedback affects ascending transmission of cutaneous neurons of the middle cuneate nucleus. Electrical stimulation of the contralateral medial lemniscus and of the skin at sites evoking responses with minimal threshold induced recurrent activation of CL cells at a latency of 1–3.5u2003ms. The lemniscal feedback activation was suppressed by increasing the stimulating intensity at the same sites, suggesting recurrent‐mediated lateral inhibition. The glycine antagonist strychnine blocked the recurrent excitatory responses while GABAA antagonists uncovered those obscured by stronger stimulation. CL cells sharing a common receptive field (RF) potentiate one another by recurrent activation and disinhibition, the disinhibition being produced by serial interactions between glycinergic and GABAergic interneurons. Conversely, CL cells with different RFs inhibit each other through recurrent GABA‐mediated inhibition. The lemniscal feedback would thus enhance the surround antagonism of a centre response by increasing the spatial resolution and the transmission of weak signals.

SENSORIMOTOR CORTICAL INFLUENCES ON CUNEATE NUCLEUS RHYTHMIC ACTIVITY IN THE ANESTHETIZED CAT

This work aimed to study whether the sensorimotor cerebral cortex spreads down its rhythmic patterns of activity to the dorsal column nuclei. Extracellular and intracellular recordings were obtained from the cuneate nucleus of chloralose-anesthetized cats. From a total of 140 neurons tested (106 cuneolemniscal), 72 showed spontaneous rhythmic activity within the slow (< 1 Hz), delta (1-4 Hz), spindle (5-15 Hz) and higher frequencies, with seven cells having the delta rhythm coupled to slow oscillations. The spindle activity recorded in the cuneate was tightly coupled to the thalamo-cortico-thalamic spindle rhythmicity. Bilateral or contralateral removal of the frontoparietal cortex abolished the cuneate slow and spindle oscillations. Oscillatory paroxysmal activity generated by fast electrical stimulation (50-100 Hz/1-2 s) of the sensorimotor cortex induced burst firing synchronized with the paroxysmal cortical spike on all the non-lemniscal neurons, and inhibitory responses also coincident with the cortical paroxysmal spike in the majority (71%) of the cuneolemniscal cells. The remaining lemniscal-projecting neurons showed bursting activity (11%) or sequences of excitation-inhibition (18%) also time-locked to the cortical paroxysmal spike. Additionally, the cerebral cortex induced coherent oscillatory activity between thalamic ventroposterolateral and cuneate neurons. Electrolytic lesion of the pyramidal tract abolished the cortically induced effects on the contralateral cuneate nucleus, as well as on the ipsilateral medial lemniscus. The results demonstrate that the sensorimotor cortex imposes its rhythmic patterns on the cuneate nucleus through the pyramidal tract, and that the corticocuneate network can generate normal and abnormal patterns of synchronized activity, such as delta waves, spindles and spike-and-wave complexes. The cuneate neurons, however, are able to generate oscillatory activity above 1 Hz in the absence of cortical input, which implies that the cerebral cortex probably imposes its rhythmicity on the cuneate by matching the intrinsic preferred oscillatory frequency of cuneate neurons.

Intracuneate mechanisms underlying primary afferent cutaneous processing in anaesthetized cats.

The cutaneous primary afferents from the upper trunk and forelimbs reach the medial cuneate nucleus in their way towards the cerebral cortex. The aim of this work was twofold: (i) to study the mechanisms used by the primary afferents to relay cutaneous information to cuneate cuneolemniscal (CL) and noncuneolemniscal (nCL) cells, and (ii) to determine the intracuneate mechanisms leading to the elaboration of the output signal by CL cells. Extracellular recordings combined with microiontophoresis demonstrated that the primary afferent cutaneous information is communicated to CL and nCL cells through AMPA, NMDA and kainate receptors. These receptors were sequentially activated: AMPA receptors participated mainly during the initial phase of the response, whereas kainate‐ and NMDA‐mediated activity predominated during a later phase. The involvement of NMDA receptors was confirmed by in vivo intracellular recordings. The cutaneous‐evoked activation of CL cells was decreased by GABA and increased by glycine acting at a strychnine‐sensitive site, indicating that glycine indirectly affects CL cells. Two subgroups of nCL cells were distinguished based on their sensitivity to iontophoretic ejection of glycine and strychnine. Overall, the results support a model whereby the primary afferent cutaneous input induces a centre‐surround antagonism in the cuneate nucleus by activating (via AMPA, NMDA and kainate receptors) and disinhibiting (via serial glycinergic–GABAergic interactions) a population of CL cells with overlapped receptive fields that at the same time inhibit (via GABAergic cells) other neighbouring CL cells with different receptive fields.

Processing Afferent Proprioceptive Information at the Main Cuneate Nucleus of Anesthetized Cats

Medial lemniscal activity decreases before and during movement, suggesting prethalamic modulation, but the underlying mechanisms are largely unknown. Here we studied the mechanisms underlying proprioceptive transmission at the midventral cuneate nucleus (mvCN) of anesthetized cats using standard extracellular recordings combined with electrical stimulation and microiontophoresis. Dual simultaneous recordings from mvCN and rostroventral cuneate (rvCN) proprioceptive neurons demonstrated that microstimulation through the rvCN recording electrode induced dual effects on mvCN projection cells: potentiation when both neurons had excitatory receptive fields in muscles acting at the same joint, and inhibition when rvCN and mvCN cells had receptive fields located in different joints. GABA and/or glycine consistently abolished mvCN spontaneous and sensory-evoked activity, an effect reversed by bicuculline and strychnine, respectively; and immunohistochemistry data revealed that cells possessing strychnine-sensitive glycine receptors were uniformly distributed throughout the cuneate nucleus. It was also found that proprioceptive mvCN projection cells sent ipsilateral collaterals to the nucleus reticularis gigantocellularis and the mesencephalic locomotor region, and had slower antidromic conduction speeds than cutaneous fibers from the more dorsally located cluster region. The data suggest that (1) the rvCN–mvCM network is functionally related to joints rather than to single muscles producing an overall potentiation of proprioceptive feedback from a moving forelimb joint while inhibiting, through GABAergic and glycinergic interneurons, deep muscular feedback from other forelimb joints; and (2) mvCN projection cells collateralizing to or through the ipsilateral reticular formation allow for bilateral spreading of ascending proprioceptive feedback information.

GABAB receptor-mediated modulation of cutaneous input at the cuneate nucleus in anesthetized cats

This study examined the modulatory influence exerted by GABA(B) receptors on the transmission of cutaneous afferent input to cuneate nucleus neurons in anesthetized cats. Electrical stimulation at the center of a receptive field activated cuneate nucleus cells at latencies of < or = 7 ms whereas stimulation at neighboring sites (receptive field edge) increased the response latency. Extracellular recording combined with microiontophoresis demonstrated that GABA(B) receptors are tonically active. Blockade of GABA(B) receptors prolonged sensory-evoked response durations and decreased times of occurrence of successive bursts whereas the agonist baclofen suppressed both these effects. Ejection of baclofen delayed the evoked response from the receptive field edge with respect to the receptive field center response and inhibited responses from the receptive field edge more effectively than responses from the receptive field center. From these results it is concluded that activation of GABA(B) receptors precludes cuneate cells from reaching firing threshold when afferent inputs are weak, spatially modulate cuneate nucleus excitability, play a major role in temporal pattern of discharges, and shape cutaneous receptive fields.

Cortico-subcortical synchronization in the chloralose-anesthetized cat

The spontaneous and paroxysmal cerebral cortical synchronized activity was used as reference to study the cortical impact exerted on subcortical neurons. The sensorimotor cortical synchronized activity spread down to subcortical structures receiving direct cortical input, including neuronal populations that originate descending rubrospinal, tectospinal and reticulospinal motor axons, and to a somatosensory relay station, the cuneate nucleus. Lesion of the pyramidal tract abolished the cortically induced synchronization of the activity of contralateral cuneate nucleus neurons.

Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms.

Non‐technical summaryu2002 The electrophysiological properties of subnucleus reticularis dorsalis (SRD) neurones were intracellularly studied. The work describes three different classes of cells differentiated by the absence (class I) or presence (classes II and III) of a fast postspike hyperpolarisation followed by depolarising sags and activation of low threshold calcium channels (class II) or type A potassium channels (class III); properties that entitle the different SRD cells to intrinsically regulate their temporal firing. All three classes showed subthreshold oscillatory activity leading to cumulative excitation (windup) in response to low frequency C‐fibre afferent input as well as to low frequency injection of depolarising currents, thus allowing SRD cells to generate windup intrinsically. The three neuronal classes sent collateral branches to the nucleus reticularis gigantocellularis (NRGc) and the spinal cord which would provide simultaneous regulation of pain‐related motor responses through the NRGc, and ascending nociceptive information via the SRD‐descending fibres ending at the spinal dorsal horn.

Electrophysiological Study of Supraspinal Input and Spinal Output of Cat's Subnucleus Reticularis Dorsalis (SRD) Neurons

This work addressed the study of subnucleus reticularis dorsalis (SRD) neurons in relation to their supraspinal input and the spinal terminating sites of their descending axons. SRD extracellular unitary recordings from anesthetized cats aimed to specifically test, 1) the rostrocaudal segmental level reached by axons of spinally projecting (SPr) neurons collateralizing or not to or through the ipsilateral nucleus reticularis gigantocellularis (NRGc), 2) whether SPr fibers bifurcate to the thalamus, and 3) the effects exerted on SRD cells by electrically stimulating the locus coeruleus, the periaqueductal grey, the nucleus raphe magnus, and the mesencephalic locomotor region. From a total of 191 SPr fibers tested to cervical 2 (Ce2), thoracic 5 (Th5) and lumbar5 (Lu5) stimulation, 81 ended between Ce2 and Th5 with 39 of them branching to or through the NRGc; 21/49 terminating between Th5 and Lu5 collateralized to or through the same nucleus, as did 34/61 reaching Lu5. The mean antidromic conduction velocity of SPr fibers slowed in the more proximal segments and increased with terminating distance along the cord. None of the 110 axons tested sent collaterals to the thalamus; instead thalamic stimulation induced long-latency polysynaptic responses in most cells but also short-latency, presumed monosynaptic, in 7.9% of the tested neurons (18/227). Antidromic and orthodromic spikes were elicited from the locus coeruleus and nucleus raphe magnus, but exclusively orthodromic responses were observed following stimulation of the periaqueductal gray or mesencephalic locomotor region. The results suggest that information from pain-and-motor-related supraspinal structures converge on SRD cells that through SPr axons having conduction velocities tuned to their length may affect rostral and caudal spinal cord neurons at fixed delays, both directly and in parallel through different descending systems. The SRD will thus play a dual functional role by simultaneously regulating dorsal horn ascending noxious information and pain-related motor responses.