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1

Local blocade of NMDA receptors in the rodent prefrontal cortex modifies oscillatory activity and c-Fos expression in the nucleus accumbens

100%
Nowak K., Meyza K., Krasicki S., Hunt M.
Acta Neurobiologiae Experimentalis
|
2009
|
tom 69
|
nr 3
In humans subanesthetic doses of noncompetitive NMDA receptor (NMDAR) antagonists can produce symptoms similar to those observed in schizophrenia. In rodents, systemic application of NMDAR antagonists produce hyperactivity, stereotypies and abnormal social interactions used to model certain features of schizophrenia. It was also shown that NMDAR antagonists induce the high frequency oscillations (HFO, 140–180 Hz) in the nucleus accumbens (NAc). Several neurophysiological models of schizophrenia emphasize the role of interactions between frontal cortical areas especially medial prefrontal cortex (mPFC) and NAc. The aim of this study was to examine the effects of local infusion of MK-801 (a selective NMDAR antagonist) in the mPFC on oscillatory activity recorded in the NAc. Experiments were performed on freely moving rats, bilaterally implanted with guides in the mPFC and an electrode in the right NAc. Bilateral administration of MK-801 to the mPFC produced a substantial increase in the power of HFO, which was associated with NMDAR antagonist-induced changes in locomotor activity and behavior. In another group of animals we examined the effects of local infusion of MK-801 into mPFC on c-Fos expression in NAc. Prominent c-Fos response was observed in the NAc in relation to saline and control groups. These results suggest that local administration of MK-801 to the mPFC modifi es oscillatory activity and c-Fos expression in the NAc.
2

Anomalous decay of power in high frequency oscillations (HFO) with distance from the source

100%
Gorski T., Hunt M., Kasicki S., Wojcik D.
Acta Neurobiologiae Experimentalis
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2015
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tom 75
|
nr Supl.
BACKGROUND AND AIMS: Brain electric potentials recorded extracellularly are generated by transmembrane currents leaving and entering active neurons. Electric charge conservation requires that these currents are balanced in every cell separately, which implies a dipolar structure of sources. We previously reported results suggesting a monopolar structure of high-frequency oscillations (135–165 Hz) generated in nucleus accumbens (NAc) which seems to be inconsistent with known physics. The goal of this study is to find out through numerical simulations if the specific morphology and spatial distribution of accumbal neurons can shed light on this paradox. METHODS: Multi-compartment models of medium spiny neuron (MSN) from NAc (based on ModelDB, accession nr 112834) were used for simulations in the NEURON simulator. We computed transmembrane activity of a population of MSNs in response to different oscillating stimuli. The sum of extracellular potentials generated by individual cells in selected points in space simulated the local field potential. Potentials were filtered in different bands to study the decay of the power with distance from the source. RESULTS: We show that the observed increased power in the HFO band can be explained by coherent spiking of population of MSNs. In all the studied frequency bands and in all directions we observe asymptotic decay with distance close to what is expected from dipolar sources (1/r^2). However, over short spatial scales, the scaling does get closer to monopolar decay (1/r). These results are compared with reevaluated decay data from Hunt et al. (2010). CONCLUSIONS: Since the numerical results are consistent with the experimental results it seems that the specific morphology and distribution of MSNs within NAc are sufficient to explain the observed anomalous decay of HFO power over intermediate distances. There is no need for consideration of additional mechanisms, for example, capacitive effects of the extracellular space.
3

State-dependent modification of high-frequnc oscillations in the rodent nucleus accumbens

100%
Hunt M., Matulewicz P., Gottesmann C., Kasicki S.
Acta Neurobiologiae Experimentalis
|
2009
|
tom 69
|
nr 3
Spontaneous high frequency oscillations (HFO) in the local fi eld potential recorded in the nucleus accumbens (NAc) are typically represented by a small peak in the power spectra in the range of 140–180 Hz. These HFO are known to occur in the awake state, but their distribution over the sleep-wake cycle has not been investigated. To address this issue we fi rstly examined the power of HFO during periods of quiet waking, slow-wave sleep (SWS) and REM sleep. Since the electrophysiological activity during general anesthesia resembles certain features of naturally occurring SWS we went on to examine the effect of pentobarbital, isofl urane or urethane anesthesia on spontaneous and ketamine-induced increases in HFO. We found that the power of spontaneous HFO decreased signifi cantly during periods of SWS with respect to both quiet waking and REM sleep. General anesthetics also reduced the power of spontaneous HFO recorded in the NAc and completely blocked the ketamine-induced increase. These fi ndings suggest that behavioural states where the generation of mental activity is most intense are associated with the presence of HFO in the NAc. In line with this, states which lead to decreased mentation, such as naturally occurring SWS and general anesthesia are associated with reductions in the power of HFO. Together these fi ndings suggest that the presence of HFO may have behaviourally meaningful consequences.
4

Evidence for regionally specific changes in high-frequency oscillations after injection of ketamine in freely moving rats

100%
Hunt M., Falinska M., Wojcik D., Kasicki S.
Acta Neurobiologiae Experimentalis
|
2009
|
tom 69
|
nr 3
We have shown previously that the NMDAR antagonists ketamine and MK-801 enhance high-frequency oscillations (140– 180 Hz, HFO) in the rat nucleus accumbens (NAc). However, it is not known whether NMDAR antagonists can modify HFO recorded in structures outside the NAc. Thus we have examined the effect of a single subanesthetic dose of ketamine (25 mg/kg) on oscillatory activity in local fi eld potentials recorded in the neuroanatomically related dorsal striatum and in the hippocampus, where spontaneous high-frequency oscillations (ripples) have been well described. We used both monopolar and bipolar recordings to evaluate oscillatory activity recorded at baseline and after injection of ketamine. In monopolar recordings ketamine-induced increases in the power of HFO were present in all structures, although the power was always substantially larger in the NAc. Bipolar recordings, known to remove common-mode input, were used in an attempt to more precisely localise the source of HFO. In all cases ketamine-induced HFO were still present in the signals recorded from the NAc, but not from the dorsal striatum or hippocampus. Notably, spontaneous sharp-wave ripples also remained in the bipolar signal from the hippocampus. In a separate study of the depth-profi le analysis of oscillatory activity we found the power of HFO was substantially larger in areas closest to the NAc. These fi ndings suggest that ketamine may produce some regionally specifi c changes in HFO.
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