NCappaert
From www.temporal-lobe.com
Natalie Cappaert
Natalie L.M. Cappaert is an Assistant Professor in the Swammerdam Institute for Life Sciences at the University of Amsterdam, The Netherlands. Her thesis work was carried out in the Hearing Research Laboratories of the University of Utrecht. During her postdoctoral training her interest shifted toward the Central Nervous System. In her recent research on the network properties of the hippocampus and the entorhinal cortex, she has applied a combination of in vitro voltage sensitive dye imaging and extracellular recordings. She currently studies theta oscillations, functional connectivity, and interneuron activity in small neuronal networks.
References
- Spatio-temporal dynamics of theta oscillations in hippocampal-entorhinal slices.
Related Articles Spatio-temporal dynamics of theta oscillations in hippocampal-entorhinal slices.
Hippocampus. 2009 Nov;19(11):1065-77
Authors: Cappaert NL, Lopes da Silva FH, Wadman WJ
Theta oscillations (4-12 Hz) are associated with learning and memory and are found in the hippocampus and the entorhinal cortex (EC). The spatio-temporal organization of rhythmic activity in the hippocampal-EC complex was investigated in vitro. The voltage sensitive absorption dye NK3630 was used to record the changes in aggregated membrane voltage simultaneously from the neuronal networks involved. Oscillatory activity at 7.0 Hz (range, 5.8-8.2) was induced in the slice with the muscarinic agonist carbachol (75-100 microM) in the presence of bicuculline (5 microM). Time relations between all recording sites were analyzed using cross-correlation functions which revealed systematic phase shifts in the theta oscillation recorded from the different entorhinal and hippocampal subregions. These phase shifts could be interpreted as propagation delays. The oscillation propagates over the slice in a characteristic spatio-temporal sequence, where the entorhinal cortex leads, followed by the subiculum and then the dentate gyrus (DG), to finally reach the CA3 and the CA1 area. The delay from dentate gyrus to the CA3 area was 12.4 +/- 1.1 ms (mean +/- s.e.m.) and from the CA3 to the CA1 region it was 10.9 +/- 1.9 ms. The propagation delays between the hippocampal subregions resemble the latencies of electrically evoked responses in the same subregions. Removing the entorhinal cortex from the slice changed the spatiotemporal pattern into a more clustered pattern with higher local synchrony. We conclude that in the slice, carbachol-induced theta oscillations are initiated in the entorhinal cortex. The EC could serve to control the information flow through the neuronal network in the subregions of the hippocampus by synchronizing and/or entraining their responses to external inputs.
PMID: 19338021 [PubMed - in process]
[?]- The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network.
Related Articles The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network.
Nat Rev Neurosci. 2009 Apr;10(4):272-82
Authors: van Strien NM, Cappaert NL, Witter MP
Converging evidence suggests that each parahippocampal and hippocampal subregion contributes uniquely to the encoding, consolidation and retrieval of declarative memories, but their precise roles remain elusive. Current functional thinking does not fully incorporate the intricately connected networks that link these subregions, owing to their organizational complexity; however, such detailed anatomical knowledge is of pivotal importance for comprehending the unique functional contribution of each subregion. We have therefore developed an interactive diagram with the aim to display all of the currently known anatomical connections of the rat parahippocampal-hippocampal network. In this Review, we integrate the existing anatomical knowledge into a concise description of this network and discuss the functional implications of some relatively underexposed connections.
PMID: 19300446 [PubMed - indexed for MEDLINE]
[?]- Spatiotemporal analyses of interactions between entorhinal and CA1 projections to the subiculum in rat brain slices.
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Related Articles Spatiotemporal analyses of interactions between entorhinal and CA1 projections to the subiculum in rat brain slices.
Hippocampus. 2007;17(10):909-21
Authors: Cappaert NL, Wadman WJ, Witter MP
The subiculum and the entorhinal cortex (EC) are important structures in processing and transmitting information between the neocortex and the hippocampus. The subiculum potentially receives information from the EC through two routes. In addition to a direct projection from EC to the subiculum, there is an indirect polysynaptic connection. The latter uses a number of possible pathways, which all converge onto the final projection from the hippocampal field CA1 to the subiculum. In this series of experiments we investigated to what extent activity in both pathways influences population activity of subicular neurons. We used voltage sensitive dyes in combined hippocampal-EC slices of the rat to measure the spatio-temporal activity patterns. To activate the two inputs to the subiculum, stimulation electrodes were placed in the stratum oriens/alveus of CA1 and in layer III of the medial EC. The response patterns evoked in the subiculum after electrical stimulation of each of these input pathways separately were compared with the response patterns after simultaneous stimulation of both areas (medial EC + CA1). A comparison of the computed added responses of the two individual stimulations with the measured responses after simultaneous stimulation suggests that both inputs are linearly added in the subiculum with very little nonlinear interactions. This strongly suggests that in the subiculum interaction at a single cell level of the direct and the indirect pathways from the EC is an unlikely scenario.
PMID: 17559098 [PubMed - indexed for MEDLINE]
[?] - Acceleration of cisplatin ototoxicity by perilymphatic application of 4-methylthiobenzoic acid.
Related Articles Acceleration of cisplatin ototoxicity by perilymphatic application of 4-methylthiobenzoic acid.
Hear Res. 2005 May;203(1-2):80-7
Authors: Cappaert NL, Klis SF, Wijbenga J, Smoorenburg GF
The antitumor agent cisplatin has dose-limiting side effects such as ototoxicity. Systemical co-treatment with anti-oxidants like 4-methylthiobenzoic acid (MTBA) and sodium thiosulfate (STS) provides protection against cisplatin ototoxicity. However, systemically administered protective agents may reduce the chemotherapeutic effect of cisplatin. Local application of the protective agents could avoid this undesirable effect. In the present study, we aimed at suppressing cisplatin-induced ototoxicity in guinea pigs by administering MTBA or STS perilymphatically through cochlear perfusion. Guinea pig cochleas were perfused for 10 min with artificial perilymph (ArtP) containing cisplatin at 0.3 mg/ml, either alone, or in combination with MTBA (0.1 or 1.0 mg/ml) or STS (0.75 or 3.0 mg/ml). The compound action potential (CAP) and the summating potential (SP), evoked by 8 kHz tone bursts, and the endocochlear potential (EP; MTBA only) were measured just before and 1, 2, 3 and 4 h after perfusion. Cisplatin gradually reduced the CAP amplitude in time. Adding MTBA only accelerated this ototoxic effect. After cisplatin treatment a decline was found in the EP, irrespective of co-treatment, i.e., addition of MTBA did not accelerate the EP decrease. In contrast to MTBA, STS ameliorated the ototoxic effect of cisplatin. In conclusion, local application of anti-oxidants can ameliorate cisplatin ototoxicity but this is not a feature of all anti-oxidants.
PMID: 15855032 [PubMed - indexed for MEDLINE]
[?]- Noise-induced hearing loss in rats.
Related Articles Noise-induced hearing loss in rats.
Noise Health. 2000;3(9):23-32
Authors: Cappaert NL, Klis SF, Muijser H, Kulig BM, Smoorenburg GF
The effect of noise exposure on the auditory system is well known from animal studies. However, most of the studies concern short-term exposure conditions. The purpose of the present research was to find the dose-effect curve for hearing loss in rats following 5 days of noise exposure. Three groups of eight Wag/Rij rats were exposed to broad band noise at levels of 90, 100 and 110 dB SPL for 8 hours/day and 5 consecutive days. An additional group of eight rats served as the control group. Between three and seven weeks after the exposure, hearing was tested by electrocochleography (CAP) and distortion product otoacoustic emissions (DPOAE). Subsequently, the cochleas were morphologically examined. Only the highest two exposure levels affected hearing. The DPOAE growth curves at 4, 8 and 16 kHz and the CAP growth curves at 4, 8, 12, 16 and 24 kHz were affected after the 110 dB SPL broad band noise. After the 100 dB SPL noise, only the 12 kHz CAP growth curve was affected. At the light-microscopic level, OHC damage was not detected in this study.
PMID: 12689440 [PubMed - as supplied by publisher]
[?]- Differential susceptibility of rats and guinea pigs to the ototoxic effects of ethyl benzene.
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Related Articles Differential susceptibility of rats and guinea pigs to the ototoxic effects of ethyl benzene.
Neurotoxicol Teratol. 2002 Jul-Aug;24(4):503-10
Authors: Cappaert NL, Klis SF, Muijser H, Kulig BM, Ravensberg LC, Smoorenburg GF
The present study was designed to compare the ototoxic effects of volatile ethyl benzene in guinea pigs and rats. Rats showed deteriorated auditory thresholds in the mid-frequency range, based on electrocochleography, after 550-ppm ethyl benzene (8 h/day, 5 days). Outer hair cell (OHC) loss was found in the corresponding cochlear regions. In contrast, guinea pigs showed no threshold shifts and no OHC loss after exposure to much higher ethyl benzene levels (2500 ppm, 6 h/day, 5 days). Subsequently, a limited study (four rats and four guinea pigs) was performed in an attempt to understand these differences in susceptibility. Ethyl benzene concentration in blood was determined in both species after exposure to 500-ppm ethyl benzene (8 h/day, 3 days). At the end of the first day, blood of the rats contained 23.2+/-0.8-microg/ml ethyl benzene, whereas the concentration in guinea pig blood was 2.8+/-0.1 microg/ml. After 3 days, the concentration in both species decreased with respect to the first day, but the ethyl benzene concentration in rat blood was still 4.3 times higher than that in guinea pig blood. Thus, the difference in susceptibility between the species may be related to the ethyl benzene concentration in blood.
PMID: 12127896 [PubMed - indexed for MEDLINE]
[?] - Simultaneous exposure to ethyl benzene and noise: synergistic effects on outer hair cells.
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Related Articles Simultaneous exposure to ethyl benzene and noise: synergistic effects on outer hair cells.
Hear Res. 2001 Dec;162(1-2):67-79
Authors: Cappaert NL, Klis SF, Muijser H, Kulig BM, Smoorenburg GF
The effects on hearing of simultaneous exposure to the ototoxic organic solvent ethyl benzene and broad-band noise were evaluated in rats. The effects of three ethyl benzene concentrations (0, 300 or 400 ppm) and three noise levels (95 or 105 dB(lin) SPL or background noise at 65 dB(lin) SPL) and all their combinations were investigated for a 5 day exposure at 8 h/day. Distortion product otoacoustic emissions and compound action potentials were affected after 105 dB noise alone, and after 105 dB noise in combination with ethyl benzene (300 and 400 ppm). However, the amount of loss for these combinations did not exceed the loss for 105 dB noise alone. Outer hair cell (OHC) loss after exposure to 300 ppm ethyl benzene was located in the third row of OHCs. At 400 ppm, the loss spread out to the second and first row of OHCs. Noise alone hardly affected the OHC counts except for a minor loss in the first row of OHCs after 105 dB SPL. Noise at 105 dB in combination with ethyl benzene at 300 and 400 ppm, however, showed OHC loss greater than the sum of the losses induced by noise and ethyl benzene alone.
PMID: 11707353 [PubMed - indexed for MEDLINE]
[?] - Ethyl benzene-induced ototoxicity in rats: a dose-dependent mid-frequency hearing loss.
Related Articles Ethyl benzene-induced ototoxicity in rats: a dose-dependent mid-frequency hearing loss.
J Assoc Res Otolaryngol. 2000 Dec;1(4):292-9
Authors: Cappaert NL, Klis SF, Baretta AB, Muijser H, Smoorenburg GF
Rats were exposed to ethyl benzene at 0, 300, 400 and 550 ppm for 8 hours/day for 5 consecutive days. Three to six weeks after the exposure, auditory function was tested by measuring compound action potentials (CAP) in the frequency range of 1-24 kHz and 2f1-f2 distortion product otoacoustic emissions (DPOAEs) in the frequency range of 4-22.6 kHz. In addition, outer hair cell (OHC) loss was quantified by histological examination. The lowest concentration ethyl benzene had no effect on any of the above measures. At 400 ppm, auditory thresholds were increased by 15 and 16 dB at 12 and 16 kHz, respectively, and at 550 ppm by 24, 31, and 22 dB at 8, 12, and 16 kHz, respectively. DPOAE amplitude growth with stimulus level was affected only after 550 ppm at 5.6, 8, and 11.3 kHz. OHC loss was found in two of the five examined locations in the cochlea. At 400 ppm, 25% OHC loss was found at the 11- and 21-kHz region. The highest concentration evoked 40% and 75% OHC loss at the 11- and 21-kHz location, respectively. Thus, the mid-frequency region of rats is affected after exposure to relatively low concentrations of ethyl benzene (400-550 ppm). These results indicate that ethyl benzene is one of the most potent ototoxic organic solvents known today.
PMID: 11547809 [PubMed - indexed for MEDLINE]
[?]- The ototoxic effects of ethyl benzene in rats.
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Related Articles The ototoxic effects of ethyl benzene in rats.
Hear Res. 1999 Nov;137(1-2):91-102
Authors: Cappaert NL, Klis SF, Muijser H, de Groot JC, Kulig BM, Smoorenburg GF
Exposure to organic solvents has been shown to be ototoxic in animals and there is evidence that these solvents can induce hearing loss in humans. In this study, the effects of inhalation of the possibly ototoxic solvent ethyl benzene on the cochlear function and morphology were evaluated using three complementary techniques: (1) reflex modification audiometry (RMA), (2) electrocochleography and (3) histological examination of the cochleas. Rats were exposed to either ethyl benzene (800 ppm, 8 h/day for 5 days) or to control conditions. The RMA threshold increased significantly by about 25 dB, 1 and 4 weeks after the exposure, irrespective of the stimulus frequency tested (4-24 kHz). Electrocochleography was performed between 8 and 11 weeks after exposure to the organic solvent. The threshold for the compound action potential increased significantly by 10-30 dB at all frequencies tested (1-24 kHz). Histological examination of the cochlea showed outer hair cell (OHC) loss, especially in the upper basal and lower middle turns (corresponding to the mid-frequency region) to an extent of 65%. We conclude that exposure to 800 ppm ethyl benzene for 8 h/day during 5 days induces hearing loss in rats due to OHC loss.
PMID: 10545637 [PubMed - indexed for MEDLINE]
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