Repetitive Cortical Stimulation Research Articles

Mechanical effects of repetitive transcranial magnetic stimulation of upper airway muscles in awake obstructive sleep apnoea subjects.

What is the central question of this study? Can repetitive transcranial magnetic stimulation (rTMS) of the genioglossus enhance the beneficial effects observed with transcranial magnetic stimulation single twitches on upper airway mechanical properties? What is the main finding and its importance? We found that both inspiratory and expiratory rTMS protocols induce a different activation pattern of upper airway muscles, with evidence for an increase in genioglossus corticomotor excitability in response to rTMS. This is of major importance because it might open the door for rTMS protocols with the goal of increasing corticomotor excitability and, thus, possibly increasing the tonic genioglossus activity, which is known to be diminished during sleep in subjects with sleep apnoea. Stimulation of upper airway (UA) muscles during sleep by isolated transcranial magnetic stimulation (TMS) twitch can improve airflow dynamics without arousal, but the effect of repetitive TMS (rTMS) on UA dynamics is unknown. Phrenic nerve magnetic stimulation (PNMS) can be used to produce painless experimental twitch-induced flow limitation during wakefulness. The aim of this study was to quantify the effects of rTMS applied during wakefulness on UA mechanical properties using PNMS in subjects with obstructive sleep apnoea (OSA). Phrenic nerve magnetic stimulation was applied to 10 subjects, with and without simultaneous rTMS, during inspiration and expiration. Flow-limitation characteristics and UA obstruction level were determined [maximal (V̇I,max)and minimal inspiratory airflow (V̇I,min),V̇I,max-V̇I,min flow drop (ΔV̇I),oropharyngeal (POro,peak ) and velopharyngeal peak pressures, oropharyngeal k1 /k2 ratios with k1 and k2 determined by the polynomial regression model between instantaneous flow and pharyngeal pressure and UA resistance]. Both genioglossus and diaphragm root mean squares and motor-evoked potential amplitudes (geniolossus, GGAmp ) and latencies were computed. A flow-limitation pattern always occurred after PNMS. A decrease in V̇I,max and an increase in ΔV̇I occurred following rTMS applied during inspiration, and POro,peak values were more negative with both inspiratory and expiratory rTMS. The GGAmp also increased significantly from the second to the last rTMS expiratory train twitch. All other parameters remained unchanged. These results suggest the following conclusions: (i)rTMS does not improve UA mechanical properties in awake subjects with OSA; (ii)the activation pattern of UA muscles differs following isolated twitch and repetitive cortical stimulation of the genioglossus; and (iii)rTMS applied during expiration induces corticomotor facilitation.

757 Evidence for Alteration in Anorectal Sensation to Non-Invasive Repetitive Lumbosacral and Cortical Magnetic Stimulation in Patients With IBS

757 Evidence for Alteration in Anorectal Sensation to Non-Invasive Repetitive Lumbosacral and Cortical Magnetic Stimulation in Patients With IBS

Trans-spinal direct current enhances corticospinal output and stimulation-evoked release of glutamate analog, D-2,3-3H-aspartic acid

Trans-spinal direct current (tsDC) stimulation is a modulator of spinal excitability and can influence cortically elicited muscle contraction in a polarity-dependent fashion. When combined with low-frequency repetitive cortical stimulation, cathodal tsDC [tsDC(-)] produces a long-term facilitation of cortically elicited muscle actions. We investigated the ability of this combined stimulation paradigm to facilitate cortically elicited muscle actions in spinal cord-injured and noninjured animals. The effect of tsDC-applied alone or in combination with repetitive spinal stimulation (rSS) on the release of the glutamate analog, D-2,3-(3)H-aspartate (D-Asp), from spinal cord preparations in vitro-was also tested. In noninjured animals, tsDC (-2 mA) reproducibly potentiated cortically elicited contractions of contralateral and ipsilateral muscles tested at various levels of baseline muscle contraction forces. Cortically elicited muscle responses in animals with contusive and hemisectioned spinal cord injuries (SCIs) were similarly potentiated. The combined paradigm of stimulation caused long-lasting potentiation of cortically elicited bilateral muscle contraction in injured and noninjured animals. Additional analysis suggests that at higher baseline forces, tsDC(-) application does not increase the rising slope of the muscle contraction but causes repeated firing of the same motor units. Both cathodal and anodal stimulations induced a significant increase of D-Asp release in vitro. The effect of the combined paradigm of stimulation (tsDC and rSS) on the concentration of extracellular D-Asp was polarity dependent. These results indicate that tsDC can powerfully modulate the responsiveness of spinal cord neurons. The results obtained from the in vitro preparation suggest that the changes in neuronal excitability were correlated with an increased concentration of extracellular glutamate. The combined paradigm of stimulation, used in our experiments, could be noninvasively applied to restore motor control in humans with SCI.

Trans-spinal direct current stimulation modulates motor cortex-induced muscle contraction in mice

The present study investigated the effect of trans-spinal direct current (tsDC) on the firing rate, pattern, and amplitude of spontaneous activity of the tibial nerve and on the magnitude of cortically elicited triceps surae (TS) muscle contractions. The effect of combined tsDC and repetitive cortical electrical stimulation (rCES) on the amplitude of cortically elicited TS twitches was also investigated. Stimulation was applied by two disk electrodes (0.79 cm(2)): one was located subcutaneously over the vertebral column (T(10)-L(1)) and was used to deliver anodal DC (a-tsDC) or cathodal DC (c-tsDC) (density range: ± 0.64 to ± 38.2 A/m(2)), whereas the other was located subcutaneously on the lateral aspect of the abdomen and served as a reference. While the application of a-tsDC significantly increased the spike frequency and amplitude of spontaneous discharges compared with c-tsDC, c-tsDC made the spontaneous discharges more rhythmic. Cortically elicited TS twitches were depressed during a-tsDC and potentiated after termination. Conversely, cortically elicited TS twitches were enhanced during c-tsDC and depressed after termination. While combined a-tsDC and rCES produced similar effects as a-tsDC alone, combined c-tsDC and rCES showed the greatest increase in cortically elicited TS twitches. tsDC appears to be a powerful neurostimulation tool that can differentially modulate spinal cord excitability and corticospinal transmission.

The effects of electric cortical stimulation on the cortical excitability in the epileptic rats

Objective To study the effects of repetitive electric cortical stimulation on the cortical excitability in the chronic epileptic rats induced by ferric chloride. Methods The chronic epileptic rats induced by intracortical injection of ferric chloride solution in the sensorimotor area were used. So we studied the effects of the low frequency (1 Hz) low amplitude (0.1 mA)and low frequency (1 Hz)high amplitude (1.0 mA)and high frequency(100 Hz)low amplitude(0.1 mA)and high frequency(100 Hz)high amplitude(1.0 mA)electric cortical stimulation on the cortical excitability by investigated the threshold and duration of cortical after discharge and the behavior score in the chronic epileptic rat. At the same time rats were treated with the sham-stimulation as control group. Results After 1 Hz and 0.1 mA repetitive electric cortical stimulation in 5 d, the cortical afterdischarge threshold (2.10 ±0.38)mA significantly ascended compared with that of the control group (1.5 ±0.33) mA, P ＜ 0.05. There was no statistic difference of behavior score and duration of cortical afterdischarge after repetitive electric cortical stimulation in 5 d compared with that of the control group. The ratio of behavior score and cortical afterdischarge threshold after 1 Hz and 0. 1 mA (1.88 ±0.60) or 1 Hz and 1.0 mA (2.18 ±0.38) repetitive electric cortical stimulation in 5 d was significantly lower than that of the control group (3.22 ±0.67, P ＜0.01 and P ＜0.05, respectively). Conclusion After the repetitive low frequency(1 Hz)low amplitude (0.1 mA)electric cortical stimulation the cortical afterdischarge threshold significantly ascended in the chronic epileptic rat induced by intracortical injection of ferric chloride solution. It means the depression of cortical excitability. The results of this study showed that electric cortical stimulation with suitable parameter can produce a suppressive effect on the epileptic rat induced by intracortical injection of ferric chloride solution. Key words: Epilepsy; Electric stimulation; Cerebral coretex; Models,animal; Rat

Cortico-striatal spike-timing dependent plasticity after activation of subcortical pathways

Cortico-striatal spike-timing dependent plasticity (STDP) is modulated by dopamine in vitro. The present study investigated STDP in vivo using alternative procedures for modulating dopaminergic inputs. Postsynaptic potentials (PSP) were evoked in intracellularly recorded spiny neurons by electrical stimulation of the contralateral motor cortex. PSPs often consisted of up to three distinct components, likely representing distinct cortico-striatal pathways. After baseline recording, bicuculline (BIC) was ejected into the superior colliculus (SC) to disinhibit visual pathways to the dopamine cells and striatum. Repetitive cortical stimulation (∼60; 0.2 Hz) was then paired with postsynaptic spike discharge induced by an intracellular current pulse, with each pairing followed 250 ms later by a light flash to the contralateral eye (n = 13). Changes in PSPs, measured as the maximal slope normalized to 5-min pre, ranged from potentiation (∼120%) to depression (∼80%). The determining factor was the relative timing between PSP components and spike: PSP components coinciding or closely following the spike tended towards potentiation, whereas PSP components preceding the spike were depressed. Importantly, STDP was only seen in experiments with successful BIC-mediated disinhibition (n = 10). Cortico-striatal high-frequency stimulation (50 pulses at 100 Hz) followed 100 ms later by a light flash did not induce more robust synaptic plasticity (n = 9). However, an elevated post-light spike rate correlated with depression across plasticity protocols (R2 = 0.55, p = 0.009, n = 11 active neurons). These results confirm that the direction of cortico-striatal plasticity is determined by the timing of pre- and postsynaptic activity and that synaptic modification is dependent on the activation of additional subcortical inputs.

Spontaneous voltage oscillations in striatal projection neurons in a rat corticostriatal slice.

In a rat corticostriatal slice, brief, suprathreshold, repetitive cortical stimulation evoked long-lasting plateau potentials in neostriatal neurons. Plateau potentials were often followed by spontaneous voltage transitions between two preferred membrane potentials. While the induction of plateau potentials was disrupted by non-NMDA and NMDA glutamate receptor antagonists, the maintenance of spontaneous voltage transitions was only blocked by NMDA receptor and L-type Ca2+ channel antagonists. The frequency and duration of depolarized events, resembling up-states described in vivo, were increased by NMDA and L-type Ca2+ channel agonists as well as by GABAA receptor and K+ channel antagonists. NMDA created a region of negative slope conductance and a positive slope crossing indicative of membrane bistability in the current-voltage relationship. NMDA-induced bistability was partially blocked by L-type Ca2+ channel antagonists. Although evoked by synaptic stimulation, plateau potentials and voltage oscillations could not be evoked by somatic current injection--suggesting a dendritic origin. These data show that NMDA and L-type Ca2+ conductances of spiny neurons are capable of rendering them bistable. This may help to support prolonged depolarizations and voltage oscillations under certain conditions.

Effects of repetitive cortical stimulation on the silent period evoked by magnetic stimulation.

The effects of repetitive transcranial stimulation (rTMS) on brain activity remain unknown. In healthy subjects, we studied the effects of rTMS on the duration of the cortical silent period (SP). Repetitive stimuli were delivered with a Cadwell High Speed Magnetic Stimulator and a figure-of-eight coil placed over the hand motor area. rTMS was delivered in trains of 11 or 20 stimuli at frequencies of 3 and 5 Hz and at stimulation intensities of 110 and 120% of motor threshold. The SP was recorded from the forearm muscles during a voluntary contraction (20% of maximum effort). rTMS delivered at a frequency of 3 and 5 Hz and intensities of 110 and 120% motor threshold prolonged the duration of the SP, without modifying either the size or the latency of the muscle-evoked potentials (MEP). A conditioning train of 11 stimuli at 3 Hz had no effect on the duration of the SP evoked by a single magnetic shock delivered 600 ms after the train. These findings show that rTMS increases the duration of the cortical SP, but does so only during the train of stimuli. rTMS probably changes the duration of the SP by facilitating cortical inhibitory interneurons.

Glutamatergic and GABAergic postsynaptic responses of striatal spiny neurons to intrastriatal and cortical stimulation recorded in slice preparations.

Glutamatergic and GABAergic responses of the neostriatal spiny neurons to intrastriatal and cortical stimulation were characterized by intracellular recording in brain slice preparations. This study also demonstrated the role of each response in the spike activity of the spiny neuron. Single neostriatal stimulation induced postsynaptic potentials consisting of multiple components. The early part of the postsynaptic potential, which was isolated by the GABAA antagonist bicuculline methiodide and the N-methyl-D-aspartate antagonist 3-(2-carboxypiperzin-4-yl)-propyl-1-phosphonic acid (CPP), was mainly an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor-mediated response. Perfusion of magnesium-free medium containing bicuculline methiodide and the AMPA/kainate antagonist 3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX) disclosed a large, slow N-methyl-D-aspartate receptor-mediated response. The N-methyl-D-aspartate response in magnesium-containing perfusing medium was small in neurons at the resting membrane potential, but became a significant component when the neurons were depolarized to subthreshold membrane potential. The duration of the N-methyl-D-aspartate response was over 300 ms. The nicotinic antagonists dihydro-beta-erythroidine hydrobromide and mecamylamine failed to change responses to single stimulation. Repetitive intrastriatal stimulation induced a large, long-duration depolarization with action potentials in the spiny neurons. This stimulation-induced response resembles that of the depolarization stage observed in anesthetized animals. Bicuculline methiodide increased the response amplitude. In contrast, CPP reduced the amplitude of the response to the below the spike generation threshold. The CPP-sensitive N-methyl-D-aspartate response was large and lasted several hundred milliseconds after the termination of repetitive stimulation. Responses of the neostriatal neurons to cortical stimulation were similar to those induced after intrastriatal stimulation. CPP greatly reduced both the response amplitude and the number of spikes triggered from the response. Bicuculline methiodide, on the other hand, greatly increased the response amplitude and the number of spikes. The AMPA/kainate response alone, which was isolated by application of bicuculline methiodide and CPP, did not induce sustained depolarization in spiny neurons to repetitive cortical stimulation. Application of NBQX diminished GABAA response to cortical stimulation. This observation indicates that, for neostriatal spiny neurons to respond with GABAA response after cortical stimulation, the AMPA/kainate response must be induced in the GABAergic secondary neurons in the neostriatum. This study indicates that the main synaptic driving forces of neostriatal spiny neurons include AMPA/kainate, N-methyl-D-aspartate and GABAA responses. Although AMPA/kainate response is the main synaptic input, the generation of the action potentials in neostriatal neurons is greatly influenced by both GABAA and N-methyl-D-aspartate responses.

Long-term Potentiation in the Striatum is Unmasked by Removing the Voltage-dependent Magnesium Block of NMDA Receptor Channels.

We have studied the effects of tetanic stimulation of the corticostriatal pathway on the amplitude of striatal excitatory synaptic potentials. Recordings were obtained from a corticostriatal slice preparation by utilizing both extracellular and intracellular techniques. Under the control condition (1.2 mM external Mg2+), excitatory postsynaptic potentials (EPSPs) evoked by cortical stimulation were reversibly blocked by 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of dl-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) ionotropic glutamate receptors, while they were not affected by 30 - 50 microM 2-amino-5-phosphonovalerate (APV), an antagonist of N-methyl-d-aspartate (NMDA) glutamate receptors. In the presence of 1.2 mM external Mg2+, tetanic activation of cortical inputs produced long-term depression (LTD) of both extracellularly and intracellularly recorded synaptic potentials. When Mg2+ was removed from the external medium, EPSP amplitude and duration increased. In Mg2+-free medium, cortically evoked EPSPs revealed an APV-sensitive component; in this condition tetanic stimulation produced long-term potentiation (LTP) of synaptic transmission. Incubation of the slices in 30 - 50 microM APV blocked striatal LTP, while it did not affect LTD. In Mg2+-free medium, incubation of the slices in 10 microM CNQX did not block the expression of striatal LTP. Intrinsic membrane properties (membrane potential, input resistance and firing pattern) of striatal neurons were altered neither by tetanic stimuli inducing LTD and LTP, nor by removal of Mg2+ from the external medium. These findings show that repetitive activation of cortical inputs can induce long-term changes of synaptic transmission in the striatum. Under control conditions NMDA receptor channels are inactivated by the voltage-dependent Mg2+ block and repetitive cortical stimulation induces LTD which does not require activation of NMDA channels. Removal of external Mg2+ deinactivates these channels and reveals a component of the EPSP which is potentiated by repetitive activation. Since the striatum has been involved in memory and in the storage of motor skills, LTD and LTP of synaptic transmission in this structure may provide the cellular substrate for motor learning and underlie the physiopathology of some movement disorders.

An iontophoretic analysis of the pharmacologic mechanisms responsible for trigeminal motoneuronal discharge during masticatory-like activity in the guinea pig

1. The effects of iontophoretic application of the excitatory amino acid antagonists kynurenic acid (KYN) and DL-2-amino-5-phosphonovaleric acid (APV), as well as the monoamines serotonin (5-HT) and norepinephrine (NE), on extracellularly recorded jaw opener motoneuron [digastric motoneuron (DIG)] discharge during cortically induced rhythmical masticatory-like activity (RMA) were examined in the anesthetized guinea pig. 2. Iontophoretic application of KYN, a broad-spectrum amino acid antagonist, suppressed the motoneuronal discharge evoked by short pulse train stimulation of the cortex for most cells tested. In contrast, iontophoretic application of APV, a specific N-methyl-D-aspartate (NMDA) antagonist, was usually without effect on the motoneuronal discharge evoked by short pulse train stimulation. 3. During RMA evoked by repetitive cortical stimulation, both KYN and APV suppressed rhythmical DIG motoneuronal discharge in many cells tested. 4. These data suggest that excitatory amino acid receptors on jaw opener motoneurons are involved in activation of RMA. It is proposed that the short-latency rapid excitation of jaw opener motoneurons, which occurs during both short pulse train cortical stimulation and RMA induced by repetitive cortical stimulation, is mediated, at least in part, by non-NMDA receptors. It is further suggested that the large-amplitude, long-duration slow rhythmical oscillations, which occur in the membrane potential of jaw opener motoneurons during RMA induced by repetitive cortical stimulation, are mediated, at least in part, by NMDA receptors. 5. Iontophoretic application of NE or 5-HT with low currents (less than 20 nA) produced a facilitation of digastric motoneuronal discharge during cycle-triggered glutamate application, short pulse train cortical stimulation, and RMA evoked by repetitive cortical stimulation. These facilitatory effects on motoneuronal discharge started within 1 min of drug application, reached a peak at approximately 3 min that persisted for several minutes after the application period, and recovered to control levels within 10-15 min. Direct application of NE or 5-HT, in the absence of chemical or synaptic activation, failed to activate these motoneurons. However, iontophoretic application of either monoamine could facilitate and bring to threshold rhythmical motoneuronal discharges during subthreshold repetitive cortical stimulation. 6. Iontophoretic application of methysergide, a 5-HT antagonist, and phentolamine, an alpha adrenoreceptor blocker, both produced a selective and reversible blockade of the facilitatory effects of 5-HT and NE, respectively, on motoneuronal discharge during cortically induced RMA. In contrast, iontophoretic application of sotalol, a beta adrenoreceptor blocker, had no effect on the NE-induced facilitation of RMA.(ABSTRACT TRUNCATED AT 400 WORDS)

Intracellular analysis of trigeminal motoneuron rhythmical activity during stimulation of pontomedullary reticular formation in anesthetized guinea pig.

1. The effects of repetitive stimulation of the nucleus pontis caudalis and nucleus gigantocellularis (PnC-Gi) of the reticular formation on jaw opener and closer motoneurons were examined. The PnC-Gi was stimulated at 75 Hz at current intensities less than 90 microA. 2. Rhythmically occurring, long-duration, depolarizing membrane potentials in jaw opener motoneurons [excitatory masticatory drive potential (E-MDP)] and long-duration hyperpolarizing membrane potentials [inhibitory masticatory drive potentials (I-MDP)] in jaw closer motoneurons were evoked by 40-Hz repetitive masticatory cortex stimulation. These potentials were completely suppressed by PnC-Gi stimulation. PnC-Gi stimulation also suppressed the short-duration, stimulus-locked depolarizations [excitatory postsynaptic potentials (EPSPs)] in jaw opener motoneurons and short-duration, stimulus-locked hyperpolarizations [inhibitory postsynaptic potentials (IPSPs)] in jaw closer motoneurons, evoked by the same repetitive cortical stimulation. 3. Short pulse train (3 pulses; 500 Hz) stimulation of the masticatory area of the cortex in the absence of rhythmical jaw movements activated the short-latency paucisynaptic corticotrigeminal pathways and evoked short-duration EPSPs and IPSPs in jaw opener and closer motoneurons, respectively. The same PnC-Gi stimulation that completely suppressed rhythmical MDPs, and stimulus-locked PSPs evoked by repetitive stimulation to the masticatory area of the cortex, produced an average reduction in PSP amplitude of 22 and 17% in jaw closer and opener motoneurons, respectively. 4. PnC-Gi stimulation produced minimal effects on the amplitude of the antidromic digastric field potential or on the intracellularly recorded antidromic digastric action potential. Moreover, PnC-Gi stimulation had little effect on jaw opener or jaw closer motoneuron membrane resting potentials in the absence of rhythmical jaw movements (RJMs). PnC-Gi stimulation produced variable effects on conductance pulses elicited in jaw opener and closer motoneurons in the absence of RJMs. 5. These results indicate that the powerful suppression of cortically evoked MDPs in opener and closer motoneurons during PnC-Gi stimulation is most likely not a result of postsynaptic inhibition of trigeminal motoneurons. It is proposed that this suppression is a result of suppression of activity in neurons responsible for masticatory rhythm generation.

Synaptic bases of cortically-induced rhythmical hypoglossal motoneuronal activity in the cat

Intracellular recordings were made from hypoglossal motoneurons during cortically-induced fictive mastication in paralyzed encéphale isolé cats. Repetitive stimulation of the masticatory area of the cerebral cortex induced rhythmical tongue movements coordinated with jaw movements. After the animal was immobilized, the cortical stimulation still induced rhythmical burst activities in the hypoglossal nerve and the digastric nerve. The burst activities in the medial and lateral branches of the hypoglossal nerve alternated rhythmically, and were in and out of phase with the burst activities of the digastric nerve, respectively. All hypoglossal motoneurons showed rhythmical intracellular potentials during repetitive cortical stimulation. The rhythmical depolarizing potentials superimposed by spike bursts appeared in phase with rhythmical bursts in either the lateral or medial branch of the hypoglossal nerve. No hyperpolarization was present between consecutive depolarizing potentials. Synaptic activation noise increased coincidentally with the depolarizing potential, indicating that EPSPs were involved in the generation of the depolarizing potential. No evidence was obtained for the existence of IPSPs during the inter-depolarizing phase by intracellular current injection. It was concluded that rhythmical bombardment of excitatory impulses to hypoglossal motoneurons was responsible for the rhythmical activity induced by repetitive stimulation of the cortical masticatory area.

Brain-stem perturbations during cortically evoked rhythmical jaw movements: effects of activation of brain-stem loci on jaw muscle cycle characteristics

The purpose of the present study was to further elucidate with the use of microstimulation techniques the influences of rostral pons and midbrain loci on the neuronal networks responsible for cortically induced rhythmical jaw movement (RJM) activity in the anesthetized guinea pig and to establish if these rostral brain-stem loci are capable of modulating the timing as well as the amplitude of rhythmical digastric (DIG) EMG activity. It was found that repetitive electrical stimulation of widespread areas of the rostral pons and mid-brain produced suppression of ongoing cortically induced rhythmical EMG activity. Prior to complete EMG suppression there was a reduction in amplitude of the DIG EMG and an increase in cycle duration. Repetitive stimulation of these suppressive loci also produced a reduction in the amplitude of the short-latency DIG EMG response produced by short pulse train stimulation of the masticatory cortex. This indicates that part of the suppression of cortically induced rhythmical EMG activity was due to a reduction in excitability of the polysynaptic short-latency pathway from cortex to DIG motoneurons. Short pulse train stimulation of these brain-stem suppressive loci during various phases of the rhythmical DIG cycle produced a phase-dependent increase in duration of the ongoing perturbed cycle. The cycles following the stimulus perturbation did not show any compensatory shortening in their durations suggesting that the stimulus produced a true resetting of the cycle. These data suggest that the brain-stem loci that produce suppression of RJMs evoked by repetitive cortical stimulation can affect the excitability of the central circuits responsible for cycle oscillation and timing as well as the excitability of the polysynaptic short-latency corticotrigeminal pathway to DIG motoneurons.

Effects of a serotonin agonist and antagonist on cortically induced rhythmical jaw movements in the anesthetized guinea pig

The effects of systemic injections of a serotonin agonist (quipazine), and antagonist (methysergide), on rhythmical jaw movements (RJMs) in the ketamine anesthetized guinea pig were examined. It was observed that quipazine, (1) significantly elevated the electrical threshold for inducing RJMs by repetitive stimulation of the masticatory cortex and (2) reduced the amplitude of the digastric and masseter EMG activity during RJMs. In contrast, the excitability of the short latency pathway from masticatory cortex to digastric motoneurons, and the excitability of the digastric reflex evoked by electrical stimulation of the mucosa of the tongue were not significantly affected by quipazine administration. Methysergide administration had little effect on the threshold for evoking RJMs, and on the excitability of the digastric reflex and short latency pathway from cortex to digastric motoneurons. These data suggest that the central pattern generator (CPG) for RJMs is not critically dependent upon serotonin receptor activation since RJMs can be induced after methysergide administration. On the other hand, excitation of the CPG by repetitive cortical stimulation can be inhibited by serotonin receptor activation. These results are interpreted as supporting our previously described model of RJM production by repetitive cortical stimulation.

Synaptic basis of cortically induced rhythmical activity of hypoglossal motoneurons in cats

Synaptic basis of the rhythmical activity induced by repetitive stimulation of the masticatory area of the cerebral cortex was studied by intracellular recording from hypoglossal motoneurons in cats, with the following results: (1) Repetitive cortical stimulation induced rhythmical tongue movements coordinated with rhythmical jaw movements. After the animal was paralyzed, the cortical stimulation still induced a rhythmically alternating efferent burst activity in the medial and lateral branches of the hypoglossal nerve; the bursts in the medial and lateral branches were in and out of phase with that of the digastric nerve, respectively. (2) In all of the recorded 36 hypoglossal motoneurons, repetitive cortical stimulation induced a rhythmical depolarizing potential superimposed by spike bursts corresponding with the rhythmical efferent burst in the hypoglossal nerve. No hyperpolarizing potential was present between the consecutive depolarizing potential. (3) Synaptic activation noise was increased coincidentally with the depolarizing potential, indicating that EPSPs were involved in the generation of the depolarizing potential. By intracellular application of either DC current or Cl-, no evidence was obtained for existence of IPSPs during the inter-excitatory phase.It was concluded that rhythmical bombardment of excitatory impulses to hypoglossal motoneurons was responsible for their rhythmical activity induced by repetitive stimulation of the cortical masticatory area.

Neuronal and glial activity during spreading depression in cerebral cortex of cat.

1. Extra- and intracellular potentials were recorded from neurons and glia during spreading depression (SD) in cerebral cortex of cats. The glial membrane depolarized during SD and the time course of depolarization was concurrent with the surface DC change of SD. The glial depolarization evoked by 20-Hz repetitive cortical stimulation disappeared during the negative DC shift of SD. Simultaneous recording of the extra- and intracellular potentials from a single glial cell with a coaxial microelectrode showed that the extracellular DC potential change was of opposite polarity to the glial intracellular potential, which suggests that the slow glial depolarization concurrent with SD is not the field potential. In contrast to glial cells, the neuronal burst discharges as well as the neuronal membrane depolarization associated with SD did not show a close relationship to SD: the neuronal membrane depolarization and discharge were frequently delayed by 10-3- s from the onset of the SD slow wave. Sometimes SD was observed without accompanying neuronal depolarization. The degree of neuronal depolarization was not always correlated with the amplitude of the negative wave of SD. 2. The effect of tetrodotoxin (TTX) on the negative DC potential of SD was examined. Simultaneous recording of glial membrane potential and the neuronal unit activity as well as extracellular DC potential and surface DC potential during SD was performed and the TTX-treated cortex was compared with the normal state. TTX did not change the DC level of the cerebral cortex. SD could be evoked by KCl when neuronal discharge was completely abolished by TTX application...

Ontogenesis of steady potential and direct cortical response in fetal sheep brain

Experiments were carried out on unanesthetized fetal sheep, 30–150 days gestational age; d-c recording showed a positive resting steady potential between the pial surface of the cortex and a reference electrode at the earliest age studied (30 days). At this time no other electrophysiological cortical phenomena could be observed. There was a slight increase of the steady potential values during the gestation period. Locally applied KCl caused a change of the steady potential from positive to negative values. The magnitude of this KCl shift was of the same order as in the adult. The steady potential could be driven into a longlasting negativity by repetitive cortical stimulation. This shift in the steady potential base line could be elicited at an age when direct cortical responses were still absent. At an age when the response could be obtained repetitive stimulation in a few experiments induced no shift or even a positive one. The first detectable direct cortical response was obtained in the middle of the gestation period and consisted of an early negative deflection (the primary potential, duration 10 msec) followed by a second negative deflection (the slow negativity, summit latency 50 msec and duration 100 msec). The response was essentially the same as that found in adult sheep and there was no obvious change of the configuration with fetal age. The stimulus threshold decreased during the gestation period to about 10% of the earliest values. Repetitive stimulation blocked the primary potential and facilitated the slow negativity in most cases. On the basis of the morphological cortical development, it is proposed that the steady potential does not depend on axially-polarized structures but is related to basic biophysical and biochemical processes and is essentially independent of later developing electrophysiological correlates to neuronal activity. The two components of the direct cortical response appear to be generated by different structures or mechanisms with different rate of maturation.