Normal Oscillations Research Articles

Anti-absence activity of mGlu1 and mGlu5 receptor enhancers and their interaction with a GABA reuptake inhibitor: Effect of local infusions in the somatosensory cortex and thalamus.

Glutamate and γ-aminobutyric acid (GABA) are the key neurotransmitter systems in the cortical-thalamocortical network, involved in normal and pathologic oscillations such as spike-wave discharges (SWDs), which characterize different forms of absence epilepsy. Metabotropic glutamate (mGlu) and GABA receptors are widely expressed within this network. Herein, we examined the effects of two selective positive allosteric modulators (PAMs) of mGlu1 and mGlu5 receptors, the GABA reuptake inhibitor, tiagabine, and their interaction in the somatosensory cortex and thalamus on SWDs in WAG/Rij rats. Male WAG/Rij rats were equipped with bilateral cannulas in the somatosensory cortex (S1po) or the ventrobasal (VB) thalamic nuclei, and with cortical electroencephalography (EEG) electrodes. Rats received a single dose of the mGlu1 receptor PAM, RO0711401, or the mGlu5 receptor PAM, VU0360172, various doses of tiagabine, or VU0360172 combined with tiagabine. Both PAMs suppressed SWDs regardless of the site of injection. Tiagabine enhanced SWDs when injected into the thalamus, but, unexpectedly, suppressed SWDs in a dose-dependent manner when injected into the cortex. Intracortical co-injection of VU0360172 and tiagabine produced slightly larger effects as compared to either VU0360172 or tiagabine alone. Intrathalamic co-injections of VU0360172 and subthreshold doses of tiagabine caused an antiabsence effect similar to that exhibited by VU0360172 alone in the first 10 min. At 30 min, however, the antiabsence effect of VU0360172 was prevented by subthreshold doses of tiagabine, and the combination produced a paradoxical proabsence effect at 40 and 50 min. These data (1) show that mGlu1 and mGlu5 receptor PAMs reduce absence seizures acting at both thalamic and cortical levels; (2) demonstrate for the first time that tiagabine, despite its established absence-enhancing effect, reduces SWDs when injected into the somatosensory cortex; and (3) indicate that the efficacy of VU0360172 in the thalamus may be critically affected by the availability of (extra)synaptic GABA.

Application of the Dyson-type boson mapping for low-lying electron excited states in molecules

In this paper, we propose a bosonization method of the system in which a quasi-particle consists of electron-hole pairs. Electron excitation energies of low-lying electron excited states are obtained by finding out the quantized normal mode oscillations around a ground state in the molecular electronic structure. These excited states are approximately considered as the collective motion states of the quasi-particles that correspond to the quantized normal mode oscillations, and each of these quasi- particles consists of the electron-hole pairs. We introduce the quasi-particle operators which create the low-lying electron excited states. These introduced quasi-particle operators, however, do not satisfy the commutation relations as bosons. Therefore, by using the Dyson-type boson mapping method, we transform these operators into those which satisfy exactly the boson commutation relations. We discuss how to map the operators of the fermion space onto the Dyson-type boson space, and obtain the Dyson-type boson representation Hamiltonian. By using this Hamiltonian, we discuss the low-lying excited states as a many-body problem of the boson system. We apply this method to the π-electrons system of the ethylene molecule, and obtain the low-lying electronexcitedstateenergiesintherandom-phaseapproximation(RPA).Inthenextstep,toimprove the accuracy of the these obtained excitation energy values, we carry out additional calculations by

A model of a breathing crack with relaxation damping

Relaxation damping is a phenomenon described recently for contact of two purely elastic bodies with infinite coefficient of friction. If a two-dimensional elastic body containing a mixed-mode crack with no sliding between the crack faces is subjected to superimposed oscillations in the normal and tangential directions, then a specific damping appears that is independent of dissipation in the elastic material. It is shown that the rate of energy dissipation due to relaxation damping is proportional to the square of the crack length and depends on the ratio of the normal local prestress to the amplitude of the normal local stress oscillations as well as on the phase shift between both oscillations. In the case of low frequency tangential loading with superimposed high frequency normal oscillations, the system acts as a tunable linear damper. Generalization of the model for the three-dimensional case is discussed.

Network Mechanisms Generating Abnormal and Normal Hippocampal High-Frequency Oscillations: A Computational Analysis.

High-frequency oscillations (HFOs) are an intriguing potential biomarker for epilepsy, typically categorized according to peak frequency as either ripples (100–250 Hz) or fast ripples (>250 Hz). In the hippocampus, fast ripples were originally thought to be more specific to epileptic tissue, but it is still very difficult to distinguish which HFOs are caused by normal versus pathological brain activity. In this study, we use a computational model of hippocampus to investigate possible network mechanisms underpinning normal ripples, pathological ripples, and fast ripples. Our results unify several prior findings regarding HFO mechanisms, and also make several new predictions regarding abnormal HFOs. We show that HFOs are generic, emergent phenomena whose characteristics reflect a wide range of connectivity and network input. Although produced by different mechanisms, both normal and abnormal HFOs generate similar ripple frequencies, underscoring that peak frequency is unable to distinguish the two. Abnormal ripples are generic phenomena that arise when input to pyramidal cells overcomes network inhibition, resulting in high-frequency, uncoordinated firing. In addition, fast ripples transiently and sporadically arise from the precise conditions that produce abnormal ripples. Lastly, we show that such abnormal conditions do not require any specific network structure to produce coherent HFOs, as even completely asynchronous activity is capable of producing abnormal ripples and fast ripples in this manner. These results provide a generic, network-based explanation for the link between pathological ripples and fast ripples, and a unifying description for the entire spectrum from normal ripples to pathological fast ripples.

Stiffness of sphere-plate contacts at MHz frequencies: dependence on normal load, oscillation amplitude, and ambient medium.

The stiffness of micron-sized sphere–plate contacts was studied by employing high frequency, tangential excitation of variable amplitude (0–20 nm). The contacts were established between glass spheres and the surface of a quartz crystal microbalance (QCM), where the resonator surface had been coated with either sputtered SiO2 or a spin-cast layer of poly(methyl methacrylate) (PMMA). The results from experiments undertaken in the dry state and in water are compared. Building on the shifts in the resonance frequency and resonance bandwidth, the instrument determines the real and the imaginary part of the contact stiffness, where the imaginary part quantifies dissipative processes. The method is closely analogous to related procedures in AFM-based metrology. The real part of the contact stiffness as a function of normal load can be fitted with the Johnson–Kendall–Roberts (JKR) model. The contact stiffness was found to increase in the presence of liquid water. This finding is tentatively explained by the rocking motion of the spheres, which couples to a squeeze flow of the water close to the contact. The loss tangent of the contact stiffness is on the order of 0.1, where the energy losses are associated with interfacial processes. At high amplitudes partial slip was found to occur. The apparent contact stiffness at large amplitude depends linearly on the amplitude, as predicted by the Cattaneo–Mindlin model. This finding is remarkable insofar, as the Cattaneo–Mindlin model assumes Coulomb friction inside the sliding region. Coulomb friction is typically viewed as a macroscopic concept, related to surface roughness. An alternative model (formulated by Savkoor), which assumes a constant frictional stress in the sliding zone independent of the normal pressure, is inconsistent with the experimental data. The apparent friction coefficients slightly increase with normal force, which can be explained by nanoroughness. In other words, contact splitting (i.e., a transport of shear stress across many small contacts, rather than a few large ones) can be exploited to reduce partial slip.

Small oscillation fault detection for a class of nonlinear systems with output measurements using deterministic learning

Early detection of small faults is an important issue in the literature of fault diagnosis. In this paper, for a class of nonlinear systems with output measurements, an approach for rapid detection of small oscillation faults is presented. Firstly, locally accurate approximations of unknown system dynamics and fault functions are achieved by combining a high gain observer and a deterministic learning (DL) theory. The obtained knowledge of system dynamics for both normal and fault modes is stored in constant RBF networks. Secondly, a bank of dynamical estimators are constructed for all the normal mode and oscillation faults. The knowledge obtained through DL is reused with a nonhigh-gain design. The occurrence of a fault can be detected if one of residual norms of a fault estimator becomes smaller than that of the normal estimator in a finite time. A rigorous analysis of the detectability properties of the proposed fault detection scheme is also given, which includes the fault detectability condition and the fault detection time. The attractions of the paper lie in that with output measurements, the knowledge of modeling uncertainty and nonlinear faults is obtained and then is utilized to enhance the sensitivity to small faults.

Disrupted light–dark cycle abolishes circadian expression of peripheral clock genes without inducing behavioral arrhythmicity in mice

The environmental light–dark (LD) cycle entrains the central circadian clock located in the suprachiasmatic nucleus (SCN) of mammals. The present study examined the effects of disrupted LD cycles on peripheral clocks in mice housed under a normal 12 h light-12 h dark cycle (LD 12:12) or an ultradian LD 3:3 cycle. Drinking behavior seemed to be free-running with a long period (26.03 h) under ultradian LD 3:3 cycles, in addition to light-induced direct suppression (masking effect). Core body temperature completely lost robust circadian rhythm and acquired a 6-h rhythm with a low amplitude under LD 3:3. Robust circadian expression of Per1, Per2, Clock and Bmal1 mRNAs was similarly flattened to intermediate levels in the liver, heart and white adipose tissue under LD 3:3. Robust circadian expression of Rev-erbα mRNA was completely damped in these tissues. Circadian expression of Dbp, a clock-controlled gene, was also disrupted in these tissues from mice housed under LD 3:3. The aberrant LD cycle seemed to induce the loss of circadian gene expression at the level of transcription, because rhythmic pre-mRNA expression of these genes was also abolished under LD 3:3. In addition to the direct effect of the aberrant LD cycle, abolished systemic time cues such as those of plasma corticosterone and body temperature might be involved in the disrupted expression of these circadian genes under LD 3:3. Our findings suggest that disrupted environmental LD cycles abolish the normal oscillation of peripheral clocks and induce internal desynchrony in mammals.

Velocity-induced neutrino oscillation and its possible implications for long baseline neutrinos

If the three types of active neutrinos possess different maximum attainable velocities and the neutrino eigenstates in the velocity basis are different from those in the flavor (and mass) basis, then this will induce a flavor oscillation in addition to the normal mass-flavor oscillation. Here we study such an oscillation scenario in three neutrino framework including also the matter effect and apply our results to demonstrate its consequences for long baseline (LBL) neutrinos. We also predict the possible signatures in terms of yields in a possible LBL neutrino experiment.

Importance of the monomer-dimer-tetramer interconversion of the clock protein KaiB in the generation of circadian oscillations in cyanobacteria.

The molecular machinery of the cyanobacterial circadian clock oscillator consists of three proteins, KaiA, KaiB and KaiC, which interact with each other to generate circadian oscillations in the presence of ATP (the in vitro KaiABC clock oscillator). KaiB comprises four subunits organized as a dimer of dimers. Our previous study suggested that, on interaction with KaiC, the tetrameric KaiB molecule dissociates into two molecules of dimeric KaiB. It is uncertain whether KaiB also exists as a monomer and whether the KaiB monomer can drive normal circadian oscillation. To address these questions, we constructed a new KaiB oligomer mutant with an N-terminal deletion, KaiB10-108 . KaiB10-108 was a monomer at 4°C but a dimer at 35°C. KaiB10-108 was able to drive normal clock oscillation in an in vitro reconstituted KaiABC clock oscillator at 25°C, but it was not able to drive normal circadian gene expression rhythms in cyanobacterial cells at 41°C. Wild-type KaiB existed in equilibrium between a dimer and tetramer at lower KaiB concentrations or in the presence of 1m NaCl. Our findings suggest that KaiB is in equilibrium between a monomer, dimer and tetramer in cyanobacterial cells.

Dissipation signals due to lateral tip oscillations in FM-AFM.

We study the coupling of lateral and normal tip oscillations and its effect on the imaging process of frequency-modulated dynamic atomic force microscopy. The coupling is induced by the interaction between tip and surface. Energy is transferred from the normal to the lateral excitation, which can be detected as damping of the cantilever oscillation. However, energy can be transferred back into the normal oscillation, if not dissipated by the usually uncontrolled mechanical damping of the lateral excitation. For certain cantilevers, this dissipation mechanism can lead to dissipation rates larger than 0.01 eV per period. The mechanism produces an atomic contrast for ionic crystals with two maxima per unit cell in a line scan.

Abstract 1110: Colorectal liver metastases induce a systemic phase shift of the biological clock

Abstract Circadian clock genes drive cyclic expression of 10-15% of the transcriptome. Disruption of the circadian clock may deregulate the cell's normal functions and can lead to carcinogenesis, indicating that clock genes also act as tumor suppressor genes. In previous work, we have shown that circadian rhythmicity is disrupted in C26 colon carcinoma cell-derived hepatic metastases, as compared to the non-cancerous tissue of the liver. It has been suggested that neoplastic tissue can influence the circadian clock of adjacent tissues, causing a tissue specific phase shift. A better understanding of how tumors affect the circadian system may help elucidate the role of the clock in cancer patients suffering from fatigue and sleep disorders. Therefore, we have examined the circadian clock in liver and kidney tissue of mice carrying hepatic C26 colon carcinoma cell metastases. Male BALB/c mice were divided into two groups. In group 1, hepatic metastases were induced by injecting C26 colorectal carcinoma cells into the spleen. Group 2 was sham operated. Three weeks after (sham) surgery, animals were sacrificed over a 24-hour period (6 time points, n=4 per time point) and liver and kidneys were collected to compare circadian rhythmicity in control and tumor bearing animals. RNA was isolated and qRT-PCR was performed to determine the expression levels of 5 clock genes (Rev-Erbα, Per1, Per2, Bmal1, Cry1) and 3 clock controlled genes (Dbp, p21 and Wee1). Liver and kidney tissue of healthy control mice showed normal 24-hour oscillations of all clock genes, consistent with normal circadian rhythmicity. Liver and kidney tissue of tumor-bearing mice, as compared to control mice, showed a marked phase difference in clock rhythms. In the liver we observed a 4-hour phase advance for Bmal1, Rev-Erbα and Dbp. In contrast in the kidney, there was a 4-hour phase delay for Bmal1, Rev-Erbα, Cry1 and DBP, and a 8 hour delay for Per2. These data show that colorectal liver metastases induce a phase advance in the liver, and a phase delay in the kidney . This suggests a systemic effect of the tumor on peripheral clocks. This difference in clock phase between tumor-bearing mice and healthy controls may provide new clues to further understand the role of the clock for fatigue and sleep problems in cancer patients, but may also give opportunities to administer chemotherapeutic treatment in a chronotherapeutical setting . Citation Format: Sander A. Huisman, F. Tamanini, A. Ahmadi, J.N.M. IJzermans, G.T.J. van der Horst, R.W.F. de Bruin. Colorectal liver metastases induce a systemic phase shift of the biological clock. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1110. doi:10.1158/1538-7445.AM2014-1110

5-Hydroxytryptamine1A receptor-activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation.

Rhythmic cortical neuronal oscillations in the gamma frequency band (30-80 Hz, gamma oscillations) have been associated with cognitive processes such as sensory perception and integration, attention, learning, and memory. Gamma oscillations are disrupted in disorders for which cognitive deficits are hallmark symptoms such as schizophrenia and Alzheimer's disease.In vitro, various neurotransmitters have been found to modulate gamma oscillations. Serotonin(5-HT) has long been known to be important for both behavioural and cognitive functions such as learning and memory. Multiple 5-HT receptor subtypes are expressed in the CA3 region of the hippocampus and high doses of 5-HT reduce the power of induced gamma oscillations.Hypothesizing that 5-HT may have cell- and receptor subtype-specific modulatory effects, we investigated the receptor subtypes, cell types and cellular mechanisms engaged by 5-HT in the modulation of gamma oscillations in mice and rats. We found that 5-HT decreases the power of kainate-induced hippocampal gamma oscillations in both species via the 5-HT1A receptor subtype. Whole-cell patch clamp recordings demonstrated that this decrease was caused by a hyperpolarization of CA3 pyramidal cells and a reduction of their firing frequency, but not by alteration of inhibitory neurotransmission. Finally, our results show that the effect on pyramidal cells is mediated via the G protein-coupled receptor inwardly rectifying potassium channel Kir3.Our findings suggest this novel cellular mechanism as a potential target for therapies that are aimed at alleviating cognitive decline by helping the brain to maintain or re-establish normal gamma oscillation levels in neuropsychiatric and neurodegenerative disorders.

Ultrafast nonadiabatic dynamics of a water dimer in femtosecond laser pulses

In the frame of the time-dependent local-density approximation coupled nonadiabatically to molecular dynamics (MD), we explored the optical absorption strength and dynamics of a water dimer in intense laser pulses with different intensities. The optical absorption spectra of a water dimer exhibiting well marked and isolated peaks agrees well with the results obtained by ab initio MD simulations. Three typical possible reaction paths are exhibited, which are normal oscillation, OH bond break and Coulomb explosion, respectively. The ionic motion shows that the water donor and the bonded OH bond are more sensitive to the laser intensity. Moreover, the water donor determines the structural reorganization of the water dimer. It is also found that the larger intensity causes higher ionization and brings forward H-transfer.

Colorectal liver metastases with a disrupted circadian rhythm phase shift the peripheral clock in liver and kidney.

Circadian clock genes regulate 10-15% of the transcriptome, and might function as tumor suppressor genes. Relatively little is known about the circadian clock in tumors and its effect on surrounding healthy tissues. Therefore, we compared the 24-hr expression levels of key circadian clock genes in liver and kidney of healthy control mice with those of mice bearing C26 colorectal tumor metastases in the liver. Metastases were induced by injection of C26 colorectal carcinoma cells into the spleen. Subsequently, tumor, liver and kidney tissue was collected around the clock to compare circadian rhythmicity. Expression levels of five clock genes (Rev-Erbα, Per1, Per2, Bmal1 and Cry1) and three clock-controlled genes (CCGs; Dbp, p21 and Wee1) were determined by qRT-PCR. Liver and kidney tissue of healthy control mice showed normal 24-hr oscillations of all clock genes and CCGs, consistent with normal circadian rhythmicity. In colorectal liver metastases, however, 24-hr oscillations were completely absent for all clock genes and CCGs except Cry1. Liver and kidney tissue of tumor-bearing mice showed a shift in clock periodicity relative to control mice. In the liver we observed a phase advance, whereas in the kidney the phase was delayed. These data show that hepatic metastases of C26 colon carcinoma with a disrupted circadian rhythm phase shift liver and kidney tissue clocks, which strongly suggests a systemic effect on peripheral clocks. The possibility that tumors may modify peripheral clocks to escape from ordinary circadian rhythms and in this way contribute to fatigue and sleep disorders in cancer patients is discussed.

Optimal by velocity two-component oscillation law of vibratory conveying devices with the electromagnetic drive

The vibratory conveying with harmonic longitudinal oscillations and normal oscillations with piecewise constant acceleration is investigated. Such oscillations provide the maximal conveying velocity in the vibratory devices with the electromagnetic drive. Formula of dependence of the conveying velocity on the dimensionless parameters is derived. Approximation of optimal normal oscillations by the polyharmonic oscillations is considered. Graphs of dependence of the velocity coefficient on the dimensionless parameters allow to determine the conveying velocity under the given amplitude and frequency of oscillations and track angle.

Community dynamics and physiology of Symbiodinium spp. before, during, and after a coral bleaching event

Community dynamics and physiology of Symbiodinium associated with Orbicella ( = Montastraea) faveolata were examined before, during, and after a thermally induced coral bleaching event in Puerto Morelos, Mexico. We combined microsampling molecular genotyping with in situ pulse‐amplitude modulated fluorometry to correlate colony variability of Symbiodinium population identities and the phenomena of partial coral bleaching. Pigmented nonbleached portions of O. ( = M.) faveolata were compared with bleached portions of the same colony. During bleaching, maximum quantum yield of photosystem II (PSII; Fv : Fm) was significantly lower and highly variable (range 0.110 to 0.680) compared with previous summers in which coral bleaching was absent (range 0.516 to 0.661) and recovery (range 0.480 to 0.716). Differential susceptibility to environmental perturbation of Fv : Fm corresponded to distinct genetic identities of Symbiodinium. Analysis of ribosomal deoxyribonucleic acid (rDNA) internal transcribed spacer 2 (ITS2) revealed regions of the coral colonies that had phylotype A3 prior to bleaching were more resistant to the bleaching perturbation than adjacent bleaching‐prone patches that harbored phylotypes B17 and C7. During environmental perturbation, regions of the colonies containing predominantly Symbiodinium phylotypes A3 or D1a retained significantly higher Fv : Fm values than adjacent regions with phylotypes B17 and C7. Following bleaching, rapid recovery of symbiotic algal densities greatly exceeded normal seasonal oscillations. During recovery we document shifts in Symbiodinium populations and increase prevalence of Symbiodinium types A3 and D1a, phylotypes known to have enhanced thermal tolerances. Thermal tolerance of Symbiodinium spp. influences the changes of coral—Symbiodinium communities during disturbance events and the dynamics of coral—Symbiodinium repopulation.

The Cyclic Loading as a Result of the Stick-Slip Motion

We investigate the influence of oscillating normal force on the frictional sliding. Frictional sliding in the case of a simple mass-spring model of Burridge and Knopoff type demonstrates stick-slip even when the friction coefficient is constant. Oscillations of the normal force in this case do not produce noticeable changes in the stick-slip sliding mode. A completely different picture is observed when the oscillations of normal force are applied to the system, which is in the state of steady sliding. In this case the normal oscillations turn the steady sliding into stick slip. A special case is observed when the normal force oscillates with the eigen frequency of the stick-slip motion. Then, no matter how small the amplitude of oscillations is the system reaches the same final stick-slip regime. The time required to reach this limiting regime is inversely proportional to the amplitude of oscillations of the normal force.

Saturn ring seismology: Looking beyond first order resonances

Some wave features found in the C-ring of Saturn appear to be excited by resonances with normal mode oscillations of the planet. The waves are found at locations in the rings where the ratio of orbital to oscillation frequencies is given by m:m+1 where m is a small integer. I suggest here that it is plausible that ring waves may also be launched at second order resonances where the frequency ratio would be m:m+2. Indeed otherwise unassociated wave features are found at such locations in the C-ring. If confirmed the association of planetary modes with additional C-ring wave features would measure additional oscillation frequencies of Saturn and improve the utility of the waves for constraining the internal structure of the planet. Second-order resonances in general do not lie near first order ring resonance locations and thus are not the explanation for the apparent frequency splitting of modes.

Resonant excitation of disk oscillations in deformed disks. VII. Stability criterion in MHD systems

Abstract In a disk with an oscillatory deformation from an axisymmetric state with frequency ωD and azimuthal wavenumber mD, two normal mode oscillations with a set of frequency and azimuthal wavenumber being (ω1, m1) and (ω2, m2) are resonantly coupled to each other through the disk deformation when the resonant conditions (ω1 + ω2 + ωD = 0 and m1 + m2 + mD = 0) are satisfied. In the case of hydrodynamical disks, the resonance amplifies the set of the oscillations if (E1/ω1)(E2/ω2) > 0 (Kato 2013b, PASJ, 65, 75), where E1 and E2 are wave energies of the two oscillations with ω1 and ω2, respectively. In this paper we show that this instability criterion is still valid even when the oscillations are ideal MHD ones in magnetized disks, if the displacements associated with the oscillations vanish on the boundary of the system.

Altered thalamic GABAA‐receptor subunit expression in the stargazer mouse model of absence epilepsy

Absence seizures, also known as petit mal seizures, arise from disruptions within the cortico-thalamocortical network. Interconnected circuits within the thalamus consisting of inhibitory neurons of the reticular thalamic nucleus (RTN) and excitatory relay neurons of the ventral posterior (VP) complex, generate normal intrathalamic oscillatory activity. The degree of synchrony in this network determines whether normal (spindle) or pathologic (spike wave) oscillations occur; however, the cellular and molecular mechanisms underlying absence seizures are complex and multifactorial and currently are not fully understood. Recent experimental evidence from rodent models suggests that regional alterations in γ-aminobutyric acid (GABA)ergic inhibition may underlie hypersynchronous oscillations featured in absence seizures. The aim of the current study was to investigate whether region-specific differences in GABAA receptor (GABAAR) subunit expression occur in the VP and RTN thalamic regions in the stargazer mouse model of absence epilepsy where the primary deficit is in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression. Immunofluorescence confocal microscopy and semiquantitative Western blot analysis were used to investigate region-specific changes in GABAAR subunits in the thalamus of the stargazer mouse model of absence epilepsy to determine whether changes in GABAergic inhibition could contribute to the mechanisms underlying seizures in this model of absence epilepsy. Immunofluorescence confocal microscopy revealed that GABAAR α1 and β2 subunits are predominantly expressed in the VP, whereas α3 and β3 subunits are localized primarily in the RTN. Semiquantitative Western blot analysis of VP and RTN samples from epileptic stargazers and their nonepileptic littermates showed that GABAAR α1 and β2 subunit expression levels in the VP were significantly increased (α1: 33%, β2: 96%) in epileptic stargazers, whereas α3 and β3 subunits in the RTN were unchanged in the epileptic mice compared to nonepileptic control littermates. These findings suggest that region-specific differences in GABAAR subunits in the thalamus of epileptic mice, specifically up-regulation of GABAARs in the thalamic relay neurons of the VP, may contribute to generation of hypersynchronous thalamocortical activity in absence seizures. Understanding region-specific differences in GABAAR subunit expression could help elucidate some of the cellular and molecular mechanisms underlying absence seizures and thereby identify targets by which drugs can modulate the frequency and severity of epileptic seizures. Ultimately, this information could be crucial for the development of more specific and effective therapeutic drugs for treatment of this form of epilepsy.