Globus Pallidus Externus Neurons Expressing parvalbumin Interconnect the Subthalamic Nucleus and Striatal Interneurons

The globus pallidus externus (GP) is a nucleus of the basal ganglia (BG), containing GABAergic projection neurons that arborize widely throughout the BG, thalamus and cortex. Ongoing work seeks to map axonal projection patterns from GP cell types, as defined by their electrophysiological and molecular properties. Here we use transgenic mice and recombinant viruses to characterize parvalbumin expressing (PV⁺) GP neurons within the BG circuit. We confirm that PV⁺ neurons 1) make up ~40% of the GP neurons 2) exhibit fast-firing spontaneous activity and 3) provide the major axonal arborization to the STN and substantia nigra reticulata/compacta (SNr/c). PV⁺ neurons also innervate the striatum. Retrograde labeling identifies ~17% of pallidostriatal neurons as PV⁺, at least a subset of which also innervate the STN and SNr. Optogenetic experiments in acute brain slices demonstrate that the PV⁺ pallidostriatal axons make potent inhibitory synapses on low threshold spiking (LTS) and fast-spiking interneurons (FS) in the striatum, but rarely on spiny projection neurons (SPNs). Thus PV⁺ GP neurons are synaptically positioned to directly coordinate activity between BG input nuclei, the striatum and STN, and thalamic-output from the SNr.     

Evidence that the nigrotegmental GABAergic projection mediates stereotypy induced by apomorphine and intranigral muscimol

The substantia nigra plays a pivotal role in the relay of output from the striatum. One neural pathway from substantia nigra projects GABAergic fibers to the caudal mesencephalic tegmentum, terminating in the vicinity of the pedunculopontine nucleus (PPN). To evaluate the functional importance of this projection in the mediation of stereotyped behaviors of striatal and nigral origin, we microinjected low doses of the GABA agonist, muscimol, bilaterally into the vicinity of the PPN. This muscimol treatment resulted in a total blockade of all stereotyped behaviors normally elicited by systemic apomorphine or by intranigral muscimol. Blockade was not observed in animals microinjected with muscimol into the dorsal reticular formation, 1 mm above the level of the PPN. Our results indicate that the nigrotegmental projection may play a crucial role in the expression of stereotyped and dyskinetic behaviors of basal ganglia origin.     

An intracellular study of pudendal afferent inputs onto tail motoneurons in the spinalized cat

Postsynaptic potentials, elicited by stimulation of the sensory pudendal (SPud) and superficial perineal nerves (SPeri) on both sides, were recorded from motoneurons innervating tail muscles in the non-anaesthetized and spinalized cat. The stimulation of SPud and SPeri on both sides predominantly produced excitatory postsynaptic potentials (EPSPs) in all kinds of tail motoneurons (70-95%). The inhibitory postsynaptic potentials (IPSPs) were often observed in motoneurons innervating ventral tail muscles (30-33%). The means of averaged central latencies of EPSPs and IPSPs ranged from 4.3 to 7.3 ms, and from 4.6 to 8.4 ms, respectively. The findings suggests that polysynaptic neuronal pathways from pudendal nerve to tail motoneurons produce tonic activities of all tail muscles to raise the tail in micturation, defecation and sexual movements which are induced by stimulation of pudendal nerves.     

Neural mechanism generating firing patterns in jaw motoneurons during the food-induced response in Aplysia kurodai

1. In each right and left buccal ganglia of Aplysia kurodai, we identified 4 premotor neurons impinging on the ipsilateral jaw-closing and -opening motoneurons. Three of them (MA1 neurons) had features of multifunctional neurons. Current-induced spikes in the MA1 neurons produced excitatory junction potentials (EJPs) in the buccal muscle fibers. In addition, tactile stimulation of the buccal muscle surface produced a train of spikes in the MA1 neurons without synaptic input. The other neuron (MA2) had only a premotor function. 2. The MA1 and MA2 neurons had similar synaptic effects on the jaw-closing and -opening motoneurons. Current-induced spikes in the premotor neurons gave rise to monosynaptic inhibitory postsynaptic potentials (IPSPs) in the ipsilateral jaw-closing motoneurons. Simultaneously, spikes in one of the MA1 neurons and the MA2 also gave rise to monosynaptic excitatory postsynaptic potentials (EPSPs) in the ipsilateral jaw-opening motoneuron. 3. The IPSPs and the EPSPs induced by spikes in the premotor neurons were reversibly blocked by d-tubocurarine and hexamethonium, respectively, suggesting that the MA1 and MA2 neurons are cholinergic. 4. When depolarizing and hyperpolarizing current pulses were passed into one premotor neuron, attenuated but similar potential changes were produced in another randomly selected premotor neuron in the same ganglion, suggesting that they are electronically coupled.     

Cerebral motoneurons mediating tentacle retraction in the land slug Ariolimax columbianus

(1) Tentacle retraction in the land slug Ariolimax columbianus can be elicited by stimulation of all nerves and connectives of the ipsi- and contralateral cerebral ganglia. (2) Six neurons in the left cerebral ganglion were classified as tentacle retraction motoneurons because their action potentials are followed one-for-one with constant delay by action potentials in the left tentacle retractor nerve and their depolarization causes retraction of the ipsilateral tentacle. The motoneurons can be identified by size, pattern of pigmentation, position, and physiological characteristics. (3) Each retractor motoneuron discharges at a rather constant rate and has more than one source of excitatory input, but no IPSPs were observed. No synaptic connections between the six retractor motoneurons were found. The nerve action potentials that correspond to each motoneurons are distinguishable by waveform and size rank. (4) Each motoneuron elicits visible contractions in a particular region of the ipsilateral retractor muscle, but the motor fields of some motoneurons overlap. Some motoneurons mediate relatively rapid contractions while others cause slower responses. (5) There is one-for-one correspondence between action potentials of the largest unit recorded extracellularly in the retractor nerve and exciatory junction potentials recorded from the retractor muscle. No evidence of a peripheral neural plexus was found in serial sections of the retractor muscle.     

Model of transient oscillatory synchronization in the locust antennal lobe

Transient pairwise synchronization of locust antennal lobe (AL) projection neurons (PNs) occurs during odor responses. In a Hodgkin-Huxley-type model of the AL, interactions between excitatory PNs and inhibitory local neurons (LNs) created coherent network oscillations during odor stimulation. GABAergic interconnections between LNs led to competition among them such that different groups of LNs oscillated with periodic Ca(2+) spikes during different 50-250 ms temporal epochs, similar to those recorded in vivo. During these epochs, LN-evoked IPSPs caused phase-locked, population oscillations in sets of postsynaptic PNs. The model shows how alternations of the inhibitory drive can temporally encode sensory information in networks of neurons without precisely tuned intrinsic oscillatory properties.     

Interaction between acoustic startle and habituated neck postural responses in seated subjects.

Postural and startle responses rapidly habituate with repeated exposures to the same stimulus, and the first exposure to a seated forward acceleration elicits a startle response in the neck muscles. Our goal was to examine how the acoustic startle response is integrated with the habituated neck postural response elicited by forward accelerations of seated subjects. In experiment 1, 14 subjects underwent 11 sequential forward accelerations followed by 5 additional sled accelerations combined with a startling tone (124-dB sound pressure level) initiated 18 ms after sled acceleration onset. During the acceleration-only trials, changes consistent with habituation occurred in the root-mean-square amplitude of the neck muscles and in the peak amplitude of five head and torso kinematic variables. The subsequent addition of the startling tone restored the amplitude of the neck muscles and four of the five kinematic variables but shortened onset of muscle activity by 9-12 ms. These shortened onset times were further explored in experiment 2, wherein 16 subjects underwent 11 acceleration-only trials followed by 15 combined acceleration-tone trials with interstimulus delays of 0, 13, 18, 23, and 28 ms. Onset times shortened further for the 0- and 13-ms delays but did not lengthen for the 23- and 28-ms delays. These temporal and spatial changes in EMG can be explained by a summation of the excitatory drive converging at or before the neck muscle motoneurons. The present observations suggest that habituation to repeated sled accelerations involves extinguishing the startle response and tuning the postural response to the whole body disturbance.     

The dorsal compartment locomotory control system in amphioxus larvae

Amphioxus myotomes consist of separate sets of superficial and deep muscle fibers, each with its own innervation, that are thought to be responsible for slow swimming and escape behavior, respectively. Tracings from serial EM sections of the anterior nerve cord in the larva show that the motoneurons and premotor interneurons controlling the superficial fibers (the dorsal compartment, or DC pathway) are linked by specialized junctions of a previously undescribed type, referred to here as juxta-reticular (JR) junctions for the characteristic presence of a cisterna of endoplasmic reticulum on each side. JR junctions link the DC motoneurons with each other, with the largest of the anterior paired neurons (LPN3s) and with one class of ipsilateral projection neurons (IPNs), but occur nowhere else. Because of the paucity of synaptic input to the DC system, larval behavior can only be explained if the JR junctions act as functional links between cells. An analysis of the pattern of cell contacts also suggests that the LPN3s are probably pacemakers for both slow and fast locomotion, but act through junctions in the former case and conventional synapses in the latter. The only major synaptic input to the DC system identified in somites 1 and 2 was from four neurons located in the cerebral vesicle, referred to here as Type 2 preinfundibular projection neurons (PPN2s). They have unusually large varicosities, arranged in series, that make periodic contacts with the DC motoneurons. More caudally, the DC motoneurons receive additional input via similar large varicosities from the receptor cells of the first dorsal ocellus, located in somite 5. The overall circuitry of the locomotory control system suggests that the PPN2s may be instrumental in sustaining slow swimming, whereas mechanical stimulation, especially of the rostrum, preferentially activates the fast mode.     

Tongue-muscle-controlling motoneurons in the Japanese toad: topography,morphology and neuronal pathways from the ‘snapping-evoking area’ in the optic tectum

As a step to clarifying the neural bases for the visually-guided prey-catching behavior in the toad, special attention was paid to the flipping movement of the tongue. Tongue-muscle-controlling motoneurons were identified antidromically, and their topographical distribution within the hypoglossal nucleus, the morphology, and the neuronal pathways from the optic tectum including the 'snapping-evoking area' (see below) to these motoneurons were investigated in paralyzed Japanese toads using intracellular recording techniques. The morphology of motoneurons innervating the tongue-protracting or retracting muscles (PMNs or RMNs respectively) was examined by means of intracellular-staining (using HRP/cobaltic lysine) and retrograde-labeling (using cobaltic lysine) methods. Both PMNs and RMNs showed an extensive spread of the branching trees of dendrites; 4 dendritic fields were distinguished: lateral/ventrolateral, dorsal/dorsolateral, medial, and in some motoneurons, contralateral dendritic fields, although there was a tendency for the dorsal/dorsolateral dendritic field to be less extensive in the PMNs than in the RMNs. The axons of both PMNs and RMNs arose from thick dendrites, ran in a ventral direction without any axon-collaterals branching off, and then entered the hypoglossal nerve. The PMNs and RMNs were distributed topographically within the hypoglossal nucleus; the RMNs were located rostrally within the nucleus, whereas the PMNs were located more caudally within it. In about 3/4 of the RMNs tested, depolarizing potentials [presumably the excitatory postsynaptic potentials (EPSPs)], on which action potentials were often superimposed, were evoked by electrical stimuli applied to the nerve branch innervating the tongue protractor. These EPSPs were temporally facilitated when the electrical stimuli were applied at short intervals (10 ms). Both PMNs and RMNs showed hyperpolarizing potentials (IPSPs) in response to single electrical stimuli of various intensities (10-200 microA) applied to the 'snapping-evoking area' (lateral/ventrolateral part of the optic tectum) on either side. These IPSPs were facilitated after repetitive electrical stimulations at short intervals (10 ms) and of weaker intensities (down to 10 microA); i.e., a temporal facilitation of the IPSPs was observed. On the other hand, large and long-lasting EPSPs which prevailed over the underlying IPSPs were evoked after repetitive electrical stimulations (a few pulses or more) at short intervals (10 ms) and of stronger intensities (generally 90 microA or more); thus, a temporal facilitation of the EPSPs was also observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Control of absence seizures induced by the pathways connected to SRN in corticothalamic system

The cerebral cortex, thalamus and basal ganglia together form an important network in the brain, which is closely related to several nerve diseases, such as parkinson disease, epilepsy seizure and so on. Absence seizure can be characterized by 2–4 Hz oscillatory activity, and it can be induced by abnormal interactions between the cerebral cortex and thalamus. Many experimental results have also shown that basal ganglia are a key neural structure, which closely links the corticothalamic system in the brain. Presently, we use a corticothalamic-basal ganglia model to study which pathways in corticothalamic system can induce absence seizures and how these oscillatory activities can be controlled by projections from the substantia nigra pars reticulata (SNr) to the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of the thalamus. By tuning the projection strength of the pathway “Excitatory pyramidal cortex-SRN”, ”SRN-Excitatory pyramidal cortex” and “SRN–TRN” respectively, different firing states including absence seizures can appear. This indicates that absence seizures can be induced by tuning the connection strength of the considered pathway. In addition, typical absence epilepsy seizure state “spike-and-slow wave discharges” can be controlled by adjusting the activation level of the SNr as the pathways SNr–SRN and SNr–TRN open independently or together. Our results emphasize the importance of basal ganglia in controlling absence seizures in the corticothalamic system, and can provide a potential idea for the clinical treatment.     

Changes in the neuronal activity in the dorsolateral pontine region caused by electrical stimulation of the brainstem regions inhibiting movement and the muscle tone

Activity of 44 mesencephalic locomotor area's (MLR) units and 38 pontine inhibitory area's (PIA) units was recorded during stimulation of the giganto-cellular reticular nucleus and oral pontine reticular nucleus inducing the hindlimb muscle tone inhibition in decerebrated rats. The muscle tone suppression was always accompanied by a decrease in the MLR and an increase in the PIA unit discharges. Stimulation of the brainstem inhibitory area seems to activate reticulospinal inhibitory system and suppress some MLR units relating to locomotion and muscle tone.     

Two excitatory motoneurons differ in quantal content of their junctional potentials in abdominal muscle fibers of the cricket,Gryllus bimaculatus

In abdominal muscles 202 and 203 of the cricket, Gryllus bimaculatus, large and small excitatory junctional potentials (l- and s-EJPs) with similar durations can be recorded from the same muscle fibers. At the normal extracellular calcium ion concentration ([Ca(2+)](o)) of 5mM, the amplitudes of l-EJPs in both muscles were larger than the threshold membrane potential for muscle action potentials, which is about -40mV. Below 0.75mM [Ca(2+)](o), the amplitudes became much smaller and were below the firing level for the action potentials. At 0.5mM, they fluctuated and decreased to 10.3 and 1.9mV in muscles 202 and 203, respectively, and at 0.25mM frequent failures occurred. The amplitudes of s-EJPs at 5mM [Ca(2+)](o) were 13.3 and 5.1mV in muscles 202 and 203, respectively, and the fluctuating amplitudes were far below the threshold for muscle action potentials. Below 0.75mM, s-EJPs were rarely observed. The relation between log(EJP amplitude) and log([Ca(2+)](o)) was linear within a certain range of [Ca(2+)](o) and the slopes of the lines for l-EJPs were about twice as steep as those for s-EJPs in both muscles. In muscle 202, the amplitude distribution of l-EJPs obtained at 0.25mM and that of s-EJPs at 0.75mM both showed peaks at once and twice the voltage at the first peak, which were coincident with the voltages at the peaks of amplitude distributions of miniature EJPs recorded simultaneously. The reversal potentials for l- and s-EJPs in muscle 202 were +1.02 and +0.22mV, respectively. In muscle 202, the decreases in amplitude of both EJPs by L-glutamate were similar and concentration-dependent. The results suggest that the difference in amplitude between l- and s-EJPs is attributable mainly to the difference in quantal contents.     

The inhibition of medullary reticulospinal neurons during the excitation of the dorsolateral portions of the pons blocking movement and muscle tonus in rats]

Hypothalamic stimulation increasing the muscle tone in hindlimbs, and excitation of the pontine dorsolateral areas inhibiting movements and the muscle tone in rats, were studied. Hypothalamic stimulation made 36.7% of the reticulospinal neurones to discharge in the form of short-latency spikes and to increase the muscle tone. The reticulospinal cells were completely inhibited by electrical stimulation of the pontine dorsolateral areas. 23.4% of the neurones only responded to the stimulation of the pontine dorsolateral areas. 35.9% of the cells did not respond to the stimulations at all. Excitation of the pontine inhibitory areas seems to prevent the descending activating effects from the brain rostral structures to spinal motor centres.     

Startle-evoked changes in diaphragmatic activity during wakefulness and sleep

Tonic inhibition of some respiratory muscles occurs as part of the generalized muscle atonia of rapid-eye-movement sleep (REMS). A second type of inhibition of the diaphragm during REMS, fractionations, consists of brief pauses in the diaphragmatic electromyogram (DIA EMG) in association with phasic events. Because motor inhibition can occur as part of the startle response, and the brain is highly activated during REMS, we hypothesized that the neural basis of the fractionations might be activation of a startle network. To test this hypothesis, tone bursts (100 dB, 20-ms duration at 15-s intervals) were applied to cats at a fixed inspiratory level in the DIA moving average during REMS, non-rapid-eye-movement sleep (NREMS), and wakefulness. Parallel sham studies (no tone applied) were obtained for each state. The response of the DIA EMG was averaged over 100 ms by using the tone pulse as a trigger, and the following parameters of the DIA EMG were measured: latency to peak and/or nadir, increment or decrement in activity, and duration of peak and/or nadir. After a tone, all five animals studied displayed a profound suppression of DIA activity during REMS (latency to nadir 42.4 +/- 10.0 ms, duration of suppression 35.9 +/- 17.6 ms). Similarly, DIA activity was suppressed in all cats during NREMS (latency to nadir 40.9 +/- 13.3 ms, duration 23.9 +/- 13.4 ms). An excitatory response was observed in only two cats during NREMS and wakefulness. The similarity of startle-induced DIA EMG pauses to spontaneous fractionations of DIA activity during REMS suggests that the latter result from activation of a central startle system.     

Control of motoneuron function and muscle tone during REM sleep, REM sleep behavior disorder and cataplexy/narcolepsy

REM sleep triggers a potent suppression of postural muscle tone - i.e., REM atonia. However, motor control during REM sleep is paradoxical because overall brain activity is maximal, but motor output is minimal. The skeletal motor system remains quiescent during REM sleep because somatic motoneurons are powerfully inactivated. Determining the mechanisms triggering loss of motoneuron function during REM sleep is important because breakdown in REM sleep motor control underlies sleep disorders such as REM sleep behavior disorder (RBD) and cataplexy/narcolepsy. For example, RBD is characterized by dramatic REM motor activation resulting in dream enactment and subsequent patient injury. In contrast, cataplexy a pathognomonic symptom of narcolepsy - is caused by the involuntary onset of REM-like atonia during wakefulness. This review highlights recent work from my laboratory that examines how motoneuron function is lost during normal REM sleep and it also identifies potential biochemical mechanisms underlying abnormal motor control in both RBD and cataplexy. First, I show that both GABAB and GABAA/glycine mediated inhibition of motoneurons is required for generating REM atonia. Next, I show that impaired GABA and glycine neurotransmission triggers the cardinal features of RBD in a transgenic mouse model. Last, I show that loss of an excitatory noradrenergic drive onto motoneurons is, at least in part, responsible for the loss of postural muscle tone during cataplexy in narcoleptic mice. Together, this research indicates that multiple transmitters systems are responsible for regulating postural muscle tone during REM sleep, RBD and cataplexy.     

Effect of histamine on duration of phases of the respiration cycle

Histamine produced either a bronchodilation or a bronchoconstriction in rats. In a 0.01-1.0 mcg/ml concentration histamine augmented the contractions amplitude in electrical stimulation of the trachea, in a 10-100 mcg/ml concentration histamine enhances the muscle tone thus decreasing the induced contractions. The histamine effects seems to be connected with its prevailing influence on different structures of the airways depending on the concentration. Its high concentrations act directly on the smooth muscle whereas its lower concentration affects receptors signaling the functional modules of the metasympathetic nervous system within the intramural ganglia of the trachea.     

Interaction of penicillin and pentobarbital with inhibitory synaptic mechanisms in neocortex

In this study we characterized the responses of neocortical neurons to iontophoretically applied gamma-aminobutyric acid (GABA) and examined how these GABA responses as well as the inhibitory postsynaptic potentials (IPSPs) were affected by the presence of penicillin or pentobarbital. Intracellular recordings were obtained from slices of rat neocortex maintained in vitro; injection of the dye Lucifer yellow indicated that recordings were primarily from pyramidal neurons. Orthodromically evoked responses were always depolarizing at the cell's resting membrane potential. Such depolarizing responses could easily be reversed in polarity by depolarizing the cell 10-15 mV, suggesting that the response consisted partly of an IPSP. In some cases, depolarization unmasked a small, short-latency excitatory postsynaptic potential (EPSP). Responses to iontophoretically applied GABA were also depolarizing at rest. Biphasic hyperpolarizing-depolarizing responses were occasionally observed upon depolarization of the neuron. Bath application of penicillin (1.7-3.4 mM) decreased the amplitude of the IPSPs and increased their time to peak, an effect associated with the development of epileptiform activity. Penicillin also reduced the maximum response to iontophoretically applied GABA without affecting the dose required to obtain a half-maximal response, suggesting a noncompetitive antagonism. Pentobarbital (100-200 microM) prolonged the time course and increased the amplitude of the IPSPs while producing a leftward shift in the GABA charge-response relation. These results suggest that the convulsant penicillin and the anticonvulsant pentobarbital have opposing actions on GABAergic inhibition in the neocortex.     

Changes in postsynaptic responses in spinal motoneurons during repetitive stimulation of the locus coeruleus

Experiments on cats anesthetized with chloralose showed that repetitive stimulation of the locus coeruleus is accompanied by a decrease in IPSPs evoked by stimulation of flexor reflex afferents in extensor motoneurons. The effect appeared 600 msec after the beginning of stimulation and reached its maximum after 1500–2000 msec. Repetitive stimulation of the locus coeruleus did not change the membrane potential and did not affect EPSPs or IPSPs evoked by stimulation of low-threshold muscle afferents; EPSPs due to activation of high-threshold cutaneous and muscle afferents likewise remained unchanged. Repetitive stimulation of more central regions of the brain stem was accompanied not only by a decrease in IPSPs evoked by stimulation of flexor reflex afferents in extensor motoneurons, but also by a decrease in amplitude of EPSPs arising in response to stimulation of these same afferents in flexor motoneurons. These effects were not connected with activation of monoaminergic structures, for unlike effects arising during stimulation of the locus coeruleus, they were also found in previously reserpinized animals.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 14, No. 1, pp. 51–59, January–February, 1982.     

Startle stimuli exert opposite effects on human cortical and spinal motor system excitability in leg muscles

Increased excitability of the spinal motor system has been observed after loud and unexpected acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in humans. The brainstem reticular formation also maintains dense anatomical interconnections with the cortical motor system. When a startling AS is delivered, prior to transcranial magnetic stimulation (TMS), the AS produces a suppression of motor evoked potential (MEP) amplitude in hand and arm muscles of healthy subjects. Here we analyzed the conditioning effect of a startling AS on MEP amplitude evoked by TMS to the primary motor leg area. Ten healthy volunteers participated in two experiments that used a conditioning-test paradigm. In the first experiment, a startling AS preceded a suprathreshold transcranial test stimulus. The interstimulus interval (ISI) varied between 20 to 160 ms. When given alone, the test stimulus evoked a MEP amplitude of approximately 0.5 mV in the slightly preinervated soleus muscle (SOL). In the second experiment, the startling AS was used to condition the size of the H-reflex in SOL muscle. Mean MEP amplitude was calculated for each ISI. The conditioning AS suppressed MEP amplitude at ISIs of 30-80 ms. By contrast, H-reflex amplitude was augmented at ISIs of 100-200 ms. In conclusions, acoustic stimulation exerts opposite and ISI-specific effects on the amplitude of MEPs and H-reflex in the SOL muscle, indicating different mechanism of auditory-to-motor interactions at cortical and spinal level of motor system.     

Bidirectional Control of Absence Seizures by the Basal Ganglia: A Computational Evidence

Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. Besides the direct coupling, anatomical evidence indicates that the cerebral cortex and thalamus also communicate indirectly through an important intermediate bridge–basal ganglia. It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. Using a biophysically based model, we demonstrate here that the typical absence seizure activities can be controlled and modulated by the direct GABAergic projections from the substantia nigra pars reticulata (SNr) to either the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of thalamus, through different biophysical mechanisms. Under certain conditions, these two types of seizure control are observed to coexist in the same network. More importantly, due to the competition between the inhibitory SNr-TRN and SNr-SRN pathways, we find that both decreasing and increasing the activation of SNr neurons from the normal level may considerably suppress the generation of spike-and-slow wave discharges in the coexistence region. Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder.