Synaptic activation of the interneurons of the thoracic portion of the spinal cord by reticulospinal fibers of the lateral funiculus

Synaptic processes evoked in various functional groups of thoracic interneurons (Th10,11) by stimulation of ipsi- and contralateral bulbar reticular formation were studied in anesthetized cats with lesions of the spinal cord that remained intact only the ipsilateral funiculus. Activation of reticulospinal fibres of the lateral funiculus with conduction velocities of 30-100 m/s evoked monosynaptic EPSPs in the following types of cells tested: monosynaptically excited by group la muscle afferents; excited by flexor reflex afferents; excited mainly by descending systems; excited by low-threshold cutaneous afferents to a less extent. All these neurons with responses to reticular stimulation were located predominantly in the central and lateral regions of Rexed's lamina VII. Most of the cells in the dorsal horn were not affected by short-latency reticulofugal influences. The only exception were 6 neurons located in the horn most dorsal laminae. Functional organization of connections between the lateral reticulospinal pathways and spinal neurons is discussed as compared to that of medial reticulo-spinal pathways as well as to the organization of "lateral" descending systems: cortico- and rubro-spinal.     

The conduction velocity of the descending spinal pathway to the renal sympathetic nerve in the cat

The conduction velocity of the descending spinal excitatory pathway to the renal sympathetic nerve was measured in five chloralose-anaesthetised, spinal cats (C1 transection). Electrical stimuli were delivered to the dorsolateral funiculus at three levels between segments C3 and T6, and responses recorded from the ipsilateral renal nerve. Spinal conduction velocity was calculated as 4.4 +/- 0.4 m/s (mean +/- SEM), from the latency difference of renal nerve volleys to stimulation at different cord levels. A contralateral pathway to the renal nerve was identified: this also ran in the dorsolateral funiculus, and crossed below segment T5. It conducted at 4.1 and 7.9 m/s (two cats). Renal preganglionic conduction velocity (greater splanchnic nerve) was 4.1 and 5.0 m/s (two cats). As the renal sympathetic nerve is functionally homogeneous, these conduction velocity measurements are of a functionally-defined sympathoexcitatory pathway.     

Presynaptic GABAB receptor activation attenuates synaptic transmission to rat sympathetic preganglionic neurons in vitro.

Intracellular recordings were made from sympathetic preganglionic neurons (SPNs) in transverse neonate rat spinal cord slices. Superfusion of gamma-aminobutyric acid (GABA; 25-100 microM) or (-)-baclofen (1-30 microM) consistently attenuated the excitatory postsynaptic potentials (EPSPs) evoked by stimulation of dorsal rootlets or lateral funiculus, without causing a significant change of the resting membrane potential and input resistance of the SPNs or of the depolarizations induced by pressure applications of glutamate; the IC50 for baclofen was 2.5 microM. When superfused at a higher concentration (greater than or equal to 500 microM) or ejected by pressure GABA caused a bicuculline-sensitive membrane hyperpolarization. The enantiomer (+)-baclofen (10-50 microM) and the GABAA agonist muscimol (1-10 microM) had no significant effect on the EPSPs. The GABAB receptor antagonist 2-hydroxy-saclofen caused a 10 fold rightward shift of the baclofen dose-response curve, whereas the GABAA receptor antagonist bicuculline (10-50 microM) was ineffective. Glycine had no significant effects on the EPSPs in the concentrations (10-100 microM) tested here. The results indicate that of the two putative inhibitory transmitters in the spinal cord GABA but not glycine depresses EPSPs evoked in the rat SPNs by acting on presynaptic GABAB receptors, the activation of which results in a reduction of excitatory transmitter release.     

Long-lasting neuronal activity in rat dorsal horn evoked by impulses in cutaneous C fibres during noxious mechanical stimulation

The responses of 44 nociceptive neurones in the lumbar dorsal horn evoked by controlled mechanical stimulation of the skin, with or without conduction block in myelinated afferent fibres, were studied in the halothane-anaesthetized rat, in order to evaluate the effects of impulses in cutaneous nociceptive C fibres on dorsal horn neurones. Continuous non-noxious pinch of the skin evoked a short-latency discharge (mean latency 15 ms) in all the 13 class 2 neurones (i.e. neurones responding to both non-noxious and noxious stimulation of the skin) tested. The short-latency discharge was followed by weak prolonged activity in 6 neurones. Following noxious pinch of the skin a prominent late discharge (peak latency 150 ms-2 s) was evoked, which in all but two class 2 neurones outlasted the stimulation period (5-10 s). The discharge evoked by noxious pinch in class 3 neurones (i.e. neurones responding to noxious stimulation only) did not usually outlast the stimulation period. In all but two nociceptive neurones tested (n = 26) the late activity evoked by noxious pinch remained, albeit at a lower frequency in some neurones, during a conduction block in A fibres2,3. Hence this late discharge is probably mainly generated by impulses in nociceptive C fibers. It is concluded that nociceptive C fibres have an important role in sustaining long-lasting activation of class 2 neurones during noxious stimulation of the skin and that long-lasting discharges in these neurones indicates tissue damage to their receptive fields.     

Supraspinal connections of neurones in the thoracic spinal cord of the cat: Ascending projections and effects of descending impulses

Single unit electrical activity has been recorded extracellularly from 103 neurones in the thoracic spinal cord of decerebrate cats. The responses of these neurons to electrical stimulation of cutaneous and visceral afferent fibres, their projection through ascending sensory pathways and the effects of descending impulses on the neurones have been studied. Of the 103 neurones recorded, 45 (43.7%) responded only to activation of cutaneous afferent fibres (‘Somatic’ neurones). Their recording sites were located mainly in laminae II, III and IV of the dorsal horn. The remaining 58 neurones (56.3%) responded to stimulation of cutaneous and visceral afferent fibres (‘Viscero-somatic’ neurones). Their recording sites were located in laminae I, V, VII and VIII of the grey matter. Sixteen neurones had axons projecting through ascending pathways: 6 were post-synaptic dorsal column cells (PSDC), 2 were spino-cervical tract cells (SCT), 5 projected through the contralateral ventro-lateral funiculus (VLQ) and 3 through the ipsilateral dorso-lateral funiculus (DLF). All PSDC cells were somatic and all VLQ neurones were viscero-somatic. Reversible spinalization of the animals by cold block resulted in a selective increase of the responses of viscero-somatic neurones to cutaneous and visceral C-fibre input. In some viscero-somatic neurones, cold block induced a reduction or abolition of the visceral input suggesting its mediation via supraspinal loops. Electrical stimulation of the ipsilateral DLF evoked non-specific inhibitions of all inputs to viscero-somatic neurones. These results are discussed in relation with the mechanisms of visceral sensation.     

Supraspinal regulation of spinal reflex discharge into cardiac sympathetic nerves

(1) In chloralose anaesthetized cats, reflex responses were recorded in inferior cardiac nerves following stimulation of intercostal nerves and hind limb afferent nerves. (2) In 80% of cats, a long latency reflex response alone was recorded, whereas, in the others, a short and long latency response was present to intercostal nerve stimulation. (3) In cats displaying only a long latency somatocardiac reflex response, damage to the ventral quadrant of the ipsilateral cervical spinal cord, through which runs a bulbospinal inhibitory pathway, resulted in the appearance of shorter latency reflexes to intercostal nerve stimulation. Lesions elsewhere in the cervical cord did not do this. (4) The characteristics of the early responses indicated that they were somatosympathetic reflexes and not dorsal root reflexes. (5) The early reflexes remained and the late reflex disappeared on subsequent complete transection of the spinal cord. The early reflexes were therefore spinal reflexes, and suppressed in the animal with cord intact. (6) Lesions at C4, which included a contralateral hemisection and a section of dorsal columns extending into the dorsal part of the lateral funiculus, abolished the inhibition of a sympathetic reflex that followed stimulation of some somatic afferent nerve fibres. These sections did not release the spinal reflex. Therefore, this reflex inhibition was not responsible for the suppression of the spinal somatosympathetic reflex. (7) The descending inhibitory influence on the segmental reflex pathway was not antagonized by strychnine, bicuculline or picrotoxin. (8) The possibility is discussed that the spinal reflex pathway into cardiac sympathetic nerves is tonically inhibited by a bulbospinal pathway originating from the classical depressor region of the ventromedial reticular formation.     

Postsynaptic processes in rubrospinal neurons of the cat brain exposed to different corticofugal influences

EPSPs of the red nucleus neurons evoked in response to stimulation of the cerebellar nucleus interpositus as well as the sensorimotor and associative parietal region of the cerebral cortex were studied in acute experiments on nembutalized cats. As in the case of the two previous structures mentioned a monosynaptic connection of the associative cortex with the rubrospinal neurons was shown to exist. Unitary EPSPs having latent periods 1.5-2.7 ms, time to peak 1.1-3.1 ms and amplitude of 0.22-0.65 mV were observed in the rubrospinal neurons in response to associative cortex stimulation. Analysis of the time parameters of the unitary EPSPs showed that synapses formed by fibres from the associative cortex are located on the somadendritic membrane of the neuron more proximally comparing with synapses formed by fibres from the sensorimotor cortex.     

Identification and properties of sub-retrofacial bulbospinal neurones: a descending cardiovascular pathway in the cat

Experiments were performed on 21 chloralose-anaesthetized, paralyzed cats to identify electrophysiologically the bulbospinal vasomotor neurones of the rostral ventrolateral medulla. Neurones were recorded from a small region close to the ventral medullary surface (sub-retrofacial nucleus), where previous studies had localized points where microinjected excitant amino acids produced large pressor responses. A total of 157 neurones in this region were antidromically activated by electrical stimulation in the spinal cord, 132 from the ipsilateral dorsolateral funiculus at lower cervical level and 25 from the intermediolateral horn at T1. Of the cells tested, 33/34 were excited by iontophoresis of homocysteic acid, indicating that recordings originated from cell bodies rather than axons. The positions of 16 were marked by dye deposition, and located histologically to the sub-retrofacial nucleus. Stimulation of baroreceptors by inflating a carotid sinus blind sac to 200 mm Hg powerfully inhibited 41/48 bulbospinal neurones tested. The threshold for this effect was 80-100 mm Hg. Baroreceptor-sensitive neurones all had axonal conduction velocities between 2 and 8.8 m/s, and within this range, all but two cells were barosensitive. Barosensitive cells were unaffected by low threshold somatosensory stimulation. Baroreceptor stimulation was still able to silence these neurones' activity even when this was raised several-fold by iontophoresis of homocysteic acid. It is argued that sub-retrofacial bulbospinal neurones probably constitute a major descending vasomotor pathway, and that baroreceptors act by inhibiting them postsynaptically.     

Fast inhibitory postsynaptic potentials and responses to inhibitory amino acids of sympathetic preganglionic neurons in the adult cat.

Intracellular recordings were obtained from sympathetic preganglionic neurons (SPNs) of the intermediolateral nucleus (IML) in slices of upper thoracic spinal cord of the anesthetized cat. A total of 44 neurons was studied. Single shock stimulation of an area of white matter dorsolateral to the IML, close to the recording electrode (< 0.5 mm), evoked fast IPSPs with rise time of 3.8 ms and 1/2 decay time of 14.7 ms (n = 12). In 17 other cells only fast EPSPs were recorded but, after suppression of the EPSPs by the excitatory amino acid receptor antagonists CNQX (20 microM) and APV (100-250 microM), fast IPSPs were unmasked. The IPSP reversed polarity at -63 mV (-67 mV in the presence of CNQX and APV). The reversal potential shifted to a less negative value when the extracellular chloride concentration was reduced. The IPSP was reversibly abolished by the GABAA receptor antagonist bicuculline in 32% of the cells, by the glycine receptor antagonist strychnine in 47% of the cells and by the combination of the two in 21% of the cells. The IPSP was abolished by TTX (0.5 microM), had constant latency and showed no failures during high frequency stimulation. The IPSP presumably resulted from the excitation of inhibitory axons and/or inhibitory neuron somata with monosynaptic connections to the SPN. Glycine and GABA (1-3 mM) produced hyperpolarization associated with decreased membrane resistance. Sixty-nine percent of cells responded to both agonists, 19% to glycine only and 12% to GABA only. The GABAB agonist baclofen (5 microM) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Longitudinal distribution of negative cord dorsum potentials following stimulation of afferent fibres in the left inferior cardiac nerve

Cord dorsum potentials were recorded along the spinal cord following electrical stimulation of afferent fibres of the left inferior cardiac nerve in chloralose anaesthetized cats. The potentials were more pronounced in spinal than in intact cats. Afferent fibres which generated cord dorsum potentials in the cervical spinal cord were localized mainly in T2 and T3 and to a smaller extent in C8 and T1 dorsal roots. The responses consisted of two waves: with short (7.0 ms; N3 wave) and long (56 ms; N4 wave) latency to the onset of potentials. N3 and N4 waves were generated by group III and group IV afferent fibres, respectively. The N3 wave was maximal at C8 and T1 spinal cord level and could be detected at least 5-6 segments rostrally from the level of afferent input responsible for its generation. The N4 wave could be detected at least 4 segments rostrally from its afferent fibre input. We conclude that afferent fibres from the left inferior cardiac nerve activate neurones in the cervical spinal cord. The implications of such finding are discussed.     

Segmental origin of sympathetic preganglionic neurones regulating the tail circulation in the rat

The spinal segments of origin of the sympathetic preganglionic neurones (SPNs) influencing the activity of sympathetic postganglionic neurones innervating the tail have been studied using a neurophysiological approach. Activity was recorded from the ventral collector nerve that carries 70% of the sympathetic fibres innervating targets within the tail and provides 80% of the innervation of the caudal ventral artery. When recording activity from the ventral collector nerve at the tail base, the largest responses were evoked following electrical stimulation within spinal segments lumbar (L) 1 and 2 and smaller responses from thoracic (T) 13 (n=5). Although similar responses to those recorded from the tail base were elicited from spinal segments L1 and L2, when activity was recorded from mid-tail only minimal responses were evoked from T13 (n=6). On average robust responses were never elicited following stimulation beyond these segments. Responses had latencies compatible with conduction over C-fibre axons and were absent following ganglionic blockade. It is concluded that SPNs influencing the tail circulation reside mainly in L1 and L2 spinal segments and there is also a substantial but lesser contribution arising from segment T13.     

Bladder and urethral sphincter responses evoked by microstimulation of S2 sacral spinal cord in spinal cord intact and chronic spinal cord injured cats

Urinary bladder and urethral sphincter responses evoked by bladder distention, ventral root stimulation, or microstimulation of S2 segment of the sacral spinal cord were investigated under alpha-chloralose anesthesia in cats with an intact spinal cord and in chronic spinal cord injured (SCI) cats 6-8 weeks after spinal cord transection at T9-T10 spinal segment. Both SCI and normal cats exhibited large amplitude reflex bladder contractions when the bladder was fully distended. SCI cats also exhibited hyperreflexic bladder contractions during filling and detrusor-sphincter dyssynergia during voiding, neither was observed in normal cats. Electrical stimulation of the ventral roots revealed that the S2 sacral spinal cord was the most effective segment for evoking large amplitude bladder contractions or voiding in both types of cats. Microstimulation with a stimulus intensity of 100 microA and duration of 30-60 s via a single microelectrode in the S2 lateral ventral horn or ventral funiculus evoked large amplitude bladder contractions with small urethral contractions in both normal and SCI cats. However, this stimulation evoked incomplete voiding due to either co-activation of the urethral sphincter or detrusor-sphincter dyssynergia. Stimulation in the S2 dorsal horn evoked large amplitude sphincter responses. The effectiveness of spinal cord microstimulation with a single electrode to induce prominent bladder and urethral sphincter responses in SCI animals demonstrates the potential for using microstimulation techniques to modulate lower urinary tract function in patients with neurogenic voiding dysfunctions.     

Study of the pathways of the cat spinal cord using the method of experimental retrograde axon transport of horseradish peroxidase]

Funicular trajectories of descending brain stem pathways in the cat were identified by means of retrograde horseradish peroxidase (HPR) transport. In sixteen cats TH1 HRP injections preceded by a large C6-C7 lesion sparing the ventral or ventrolateral funiculi and by such a lesion sparing the dorsolateral funiculus were made. It was found that the descending fibres from the nucleus locus coeruleus and the nucleus subcoeruleus are distributed ipsilaterally through the ventrolateral funiculus. The fibres from the hypothalamus which descend throughout the spinal cord are located mainly in the lateral funiculus, but some of them also descend through the ventral and dorsolateral funiculi. A diagram summarizing the distribution of the descending fibres from the various brain stem cell groups over the different C6-C7 funiculi is presented.     

Inhibitory influences of reticulospinal fibers of the lateral funiculus on neurons of the reflex arc of the thoracic region of the spinal cord

Experiments on anesthetized cats with partial lesions of the spinal cord show that reticulospinal pathways in the ventral part of the lateral funiculus take part in the polysynaptic reflex inhibition caused by stimulation of ipsi- and contralateral reticular formation. The reticulofugal volley in the ventrolateral funiculus produced relatively short (up to 7 ms) inhibitory PSP in some motoneurons of the internal intercostal nerve and at the same time long-lasting depression of EPSPs evoked by high-threshold segmentary afferents. This volley also caused inhibitory PSP in segmental interneurons (in 14 out of 91, i.e. 15.5%). The IPSPs lasted no longer than 100 ms, while the segmentary excitatory responses of 21 out of 43 interneurons were depressed for 120-500 ms. The described inhibitory action of the lateral reticulospinal system on segmentary reflex pathways is suggested to be caused by several synaptic mechanisms which do not necessarily include hyperpolarization of spinal neurons. Possible mechanisms of such inhibition are discussed.     

Evaluation of transcranial magnetic stimulation for investigating transmission in descending motor tracts in the rat

In the rat, non-invasive transcranial magnetic stimulation (TMS) has shown promise for evaluation of transmission through the spinal cord before and after repair strategies, but it is still unclear which pathways are activated by TMS. The aim of the present study was therefore to identify these pathways and to analyse the effect of TMS on spinal neurons. In 19 rats, TMS evoked responses bilaterally in forelimb (biceps brachii; BB) and hindlimb muscles (tibialis anterior). The latency and amplitude of these motor-evoked responses (MEPs) were highly variable and depended strongly on the coil position and the stimulation intensity. The most frequently observed latencies for the BB MEPs could be divided into three groups: 3-6 ms, 8-12 ms and 14-18 ms. Lesions in the dorsal columns, which destroyed the corticospinal tract at C2 and C5, significantly depressed MEPs in the mid- and high-latency ranges, but not those in the low-latency range. Lesions in the dorsolateral funiculus, which interrupted the rubrospinal tract, had no effect on MEPs in any of the latency ranges. By contrast, bilateral lesion of the reticulospinal tract and other ventro-laterally located descending pathways abolished all responses. Intracellular recordings from 54 cervical motoneurons in five rats revealed that TMS evoked excitatory postsynaptic potentials (EPSPs) at latencies that corresponded well with those of the BB MEPs. The short-latency EPSPs had rise times of around 1 ms, suggesting that they were mediated by a monosynaptic pathway. EPSPs with longer latencies had considerably longer rise times, which indicated conduction through polysynaptic pathways. Selective electrical stimulation of the pyramidal tract in the brainstem was performed in seven rats, where intracellular recordings from 70 motoneurons revealed that the earliest EPSPs and MEPs evoked by TMS were not mediated by the corticospinal tract, but by other descending motor pathways. Together, these results showed that in the rat TMS activates several descending pathways that converge on common spinal interneurons and motoneurons. Our observations confirm that the corticospinal tract has weak (and indirect) projections to cervical spinal motoneurons.     

Sympathetic preganglionic neurones in neonatal rat spinal cord in vitro: electrophysiological characteristics and the effects of selective excitatory amino acid receptor agonists

Intracellular recordings were made from 52 lateral horn neurones in thin slices of neonatal rat thoracolumbar spinal cord. Of these neurones 12 were spontaneously active and the remainder silent. A number of these cells could be activated antidromically by stimulation of ventral roots. The conduction velocity of the antidromic potential was estimated to be 0.9–2 m/s which is within the range reported for axons of sympathetic preganglionic neurones (SPNs). The membrane properties of antidromically identified SPNs were similar to other lateral horn neurones included in this study and comparable to those reported for SPNs by others. Spontaneous burst firing was recorded in 3 neurones and activity in a further 5 neurones was characterized by the discharge of an action potential followed by an afterhyperpolarization potential (AHP) of peak amplitude 3–13 mV and duration 0.5–4 s. The AHP had an initial fast component (fAHP) which was sensitive to the potassium channel blocker tetraethylammonium (TEA), and a second slower component (sAHP) which was both sensitive to extracellular calcium and TEA. The effects of the selective excitatory amino acid receptor agonists N-methyl-d-aspartate (NMDA), kainate and quisqualate were investigated by superfusion of the agonists, at known concentrations (100 nM to 100 μM). These agonists induced concentration-dependent depolarizations which were primarily associated with a reduction in neuronal input resistance. NMDA-induced depolarizations were potentiated in the absence of magnesium. In a number of neurones NMDA, kainate and quisqualate (1–50 μM) induced, in addition to a depolarizing response, the discharge of small (1.5–6.5 mV), brief (7–20 ms) IPSPs which were reversed just below resting membrane potential at −64 mV. These results suggest that both NMDA and non-NMDA receptors may have an important role in the excitation of SPNs and of inhibitory interneurones presynaptic to SPNs.     

Lesions of dorsolateral funiculi (DLF) do not affect the depressive effects of systemic morphine upon dorsal horn convergent neuronal activities related to pain in the rat

It has been shown that morphine could interact with supraspinal inhibitory controls which modulate the transmission of nociceptive messages at the spinal level. However, the way in which such interactions occur is still a subject of controversy. Based on behavioural experiments, it has been proposed that systemic morphine increases descending inhibitory controls travelling via the dorsolateral funiculus (DLF). To directly test this hypothesis from an electrophysiological standpoint, we have investigated the effects of morphine upon C-fibre responses of dorsal horn convergent neurones in rats with bilateral lesions of the DLF. Previous studies by our group have shown that 6 mg/kg morphine chlorhydrate was the intravenous mean effective dose for depressing by 50% (ED50) the C-fibre evoked responses of convergent neurones recorded at the lumbar level. In the present work, the effects of 6 mg/kg morphine were investigated under identical experimental conditions, except that a bilateral destruction of the dorsolateral funiculus (DLF) was performed previously. These lesions did not change the mean C-fibre evoked responses. Following morphine administration, the C-fibre evoked responses were depressed by 47.1 ± 10.1% (n= 13) and reversal of these effects by naloxone was always observed. The A-fibre evoked responses, cuncurrently recorded, were not modified by the drug. As the depressive effects observed with this dose of morphine appear to be essentially of the same magnitude as those previously found in the intact or spinal preparations, we conclude that the DLF is not involved in the depressive effects of systemic morphine on dorsal horn convergent neurones.     

Long C3-C5 propriospinal neurones in the cat

Intracellular recording was made in the C3-C5 segments of cats from cells identified as long propriospinal neurones (PNs) by antidromic activation from the lower thoracic segments. The cell bodies were in laminae VII and VIII and their ventrally located axons were either uncrossed or crossed. Stimulation of higher motor centres revealed monosynaptic excitatory postsynaptic potentials (EPSPs) from cortico-, rubro-, tecto-, reticulo-, interstitio-, fastigio- and trigeminospinal fibres. Monosynaptic inhibitory postsynaptic potentials (IPSPs) were evoked from reticulospinal fibres. These PSPs were in addition to the separately described effects from the vestibular nuclei. Monosynaptic EPSPs were also evoked in some cells from neck or forelimb afferents and disynaptic EPSPs or IPSPs from forelimb afferents.     

The cortically evoked secondary depolarization affects the integrative properties of thalamic reticular neurons

Corticothalamic terminals on thalamic reticular (RE) neurons account for most synapses from afferent pathways onto this nucleus and these inputs are more powerful than those from axon collaterals of thalamocortical neurons. Given the supremacy of cortical inputs, we analysed here the characteristics and possible mechanisms underlying a secondary component of the cortically elicited depolarization in RE neurons, recorded in cats under barbiturate anesthesia. Electrical stimulation of corticothalamic axons in the internal capsule evoked fixed and short-latency excitatory postsynaptic potentials (EPSPs) that, by increasing stimulation intensity and at hyperpolarized levels (< -70 mV), developed into low-threshold spikes and spindle oscillations. The threshold for spindle oscillations was 60% higher than that required for evoking minimal EPSPs. The evoked EPSPs included a secondary depolarizing component, which appeared approximately 5 ms after the peak of the initial component and was voltage dependent, i.e. most prominent between -70 mV and -85 mV, while being greatly reduced or absent at more hyperpolarized levels. The secondary depolarizing component was sensitive to QX-314 in the recording micropipette. We suggest that the secondary component of cortically evoked EPSPs in RE neurons is due to the dendritic activation of T-currents, with a probable contribution of the persistent Na+ current. This late component affected the integrative properties of RE neurons, including their spiking output and temporal summation of incoming cortical inputs.     

Responses of globus pallidus neurons to cortical stimulation: intracellular study in the rat.

The responses of globus pallidus (GP) neurons to stimulation of the sensorimotor cortex, the neostriatum, and the subthalamic nucleus were intracellularly recorded in anesthetized rats. Stimulation of the cortex evoked a sequence of postsynaptic responses including an initial short EPSP, a short IPSP, and a late EPSP with multiple spikes in most of the repetitively firing GP neurons. The response pattern was very similar to those evoked by striatal stimulation, except that the latencies were longer. An acute knife cut placed immediately caudal to the substantia nigra caused no significant change in the responses to cortical and striatal stimulation. Stimulation of the subthalamic nucleus evoked a short latency EPSP overlapped with an IPSP. The polarity of all the IPSPs was reversed by a Cl- injection. A systemic injection of picrotoxin abolished all the IPSPs and unmasked large depolarizations with multiple spikes. An ibotenic acid lesion of the subthalamic nucleus eliminated both the initial short latency and late EPSPs to cortical and striatal stimulation and disclosed a prominent IPSP. Stimulation of the lesioned subthalamic nucleus also evoked large, short latency IPSPs without noticeable EPSPs. These results indicate that (i) the IPSPs evoked by cortical, striatal, and subthalamic stimulation were mediated by a GABAA receptor, (ii) both the initial and late EPSPs to cortical and striatal stimulation involved activation of the subthalamic nucleus but not brainstem nuclei, and (iii) cortically derived signals mediated through the neostriatum (i.e. long latency IPSPs) and the subthalamic nucleus (i.e. short latency EPSPs) converged on most GP neurons.