1 Physiologisches Institut III, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany and , 2 Institute of Pathological Physiology, Sasinkova 4, SK-811 08 Bratislava, Slovak Republic
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Abstract |
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Introduction |
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Critical periods also appear to exist in the auditory system. Language development, dependent on the auditory system, is known to have a critical period [for a review see (Skuse, 1993)]. Transient expression of acetylcholinesterase, seen in the rat visual and somatosensory cortices during their critical period, is also found in the auditory cortex with a similar time-course (Robertson, 1987
; Robertson et al., 1991
). The cholinergic system is known to be involved in learning effects in the auditory cortex (Juliano, 1998
; Kilgard and Merzenich, 1998
; Weinberger, 1998
) and might play a role in the formation of thalamocortical connections. Lesion studies, in the cochlea as well as in the central nervous system, support the idea of a critical period in auditory development (Harrison et al., 1991
) [for a review of central lesions see e.g. (Wakita and Watanabe, 1997
)], as do the data from congenitally deaf individuals equipped with cochlear implants (Eddington et al., 1978
; Busby et al., 1992
; Fryauf-Bertschy et al., 1997
). If congenitally deaf patients are implanted during childhood they can gain complete language competence. However, congenitally deaf patients implanted as adults have significantly poorer auditory performance and do not gain comparable language competence. The deficits in the auditory system responsible for their poor performance remain to be explored.
The congenitally deaf white cat (CDC) is a suitable naturally occurring model of congenital deafness (Larsen and Kirchhoff, 1992; Saada et al., 1996
; Heid et al., 1998
). CDCs suffer from a dysplasia of the organ of Corti. The inner and outer hair cells are completely missing at an age when hearing starts in normal animals. A similar degeneration (Scheibe dysplasia) is most frequently found in human congenital nonsyndromic sensorineural hearing loss. No further neurological defects have been discovered so far in CDCs (Saada et al., 1996
). In contrast to pharmacologically deafened animals (Leake-Jones et al., 1982
; Xu et al., 1993
; Hardie and Shepherd, 1999
), the primary afferents of CDCs are relatively well preserved (90% preservation after 2 years in the basal half turn of the cochlea) (Heid et al., 1998
). Only the basal halfturn of the cat cochlea can be reached by cochlear implant electrical stimulation (Hartmann et al., 1997
; Kral et al., 1998
). Thus the effect of spiral ganglion degeneration does not have to be taken into account in the CDCs, as is the case in pharmacologically deafened animals (Hardie and Shepherd, 1999
).
Because of the early degeneration of the cochlea, the auditory cortex of the CDC does not receive any sound-evoked input. Developmental processes dependent on acoustic stimulation cannot take place. However, the brainstem of these animals is anatomically well developed (Heid et al., 1997). The afferent connections of the brainstem show nucleotopic organization (Heid et al., 1997
). In their auditory cortex, a rudimentary cochleotopy has been demonstrated by single unit recordings and middle-latency responses (Hartmann et al., 1997
).
In the present paper, the question of functional deficits in the acoustically naive auditory cortex is addressed. Indications that abnormalities in neurons, synapses and neuronal connections appear as a consequence of auditory deprivation have been found (Neville and Lawson, 1987; McMullen et al., 1988
; Larsen and Kirchhoff, 1992
; Chugani et al., 1996
; Ponton et al., 1996
; Heid et al., 1997
; Kotak and Sanes, 1997
; Moore et al., 1997
; Niparko and Finger, 1997
; Hardie et al., 1998
; Ryugo et al., 1998
; Nishimura et al., 1999
; Hardie and Shepherd, 1999
; Wurth et al., 1999
). Nevertheless, functional data about the deprivation effects on the auditory cortex are not yet available. According to the work of Mitani et al. (Mitani et al., 1985
) and Prieto et al. (Prieto et al., 1994
), the different layers of the auditory cortex are activated in a well-defined temporal sequence (Aitkin, 1990
). Is this pattern established in congenitally deaf animals? To answer this question, gross synaptic currents in different layers of the auditory cortex were compared between electrically stimulated normal hearing cats and CDCs using current source density (CSD) analyses.
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Materials and Methods |
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Two adult normal hearing cats (14 and 21 months of age) and five CDCs (aged between 6 and 29 months) were used. Deafness of the CDCs was verified by the absence of auditory evoked potentials in regular screenings from the age of 4 weeks with intensities up to 125 dB SPL [for details see (Heid et al., 1998)]. Control hearing cats were deafened by an acute intracochlear infusion of neomycin sulphate (1 ml over 5 min) at the beginning of the recordings. The experiments were licensed by the Hessian State Authorities.
Anaesthesia
The animals were preanaesthetized with ketamine (24.5 mg/kg body wt) and xylazine (2.1 mg/kg body wt) i.m. A modified Ringer's solution was applied through a venous catheter (Hartmann et al., 1984, 1997
; Kral et al., 1998
). Anaesthesia was maintained by additional doses of ketamine. In two CDCs volatile anaesthesia was used after tracheotomy (isoflurane, O2:N2O = 1:1). A constant, light level of anaesthesia was ensured by monitoring the EEG, muscle tone, heart rate, end-tidal CO2, spontaneous movements and withdrawal reflex in response to twitching the forepaw with forceps [details are given in (Kral et al., 1999
)].
Surgical Technique and Implant Electrodes
Details of the surgery are given in Hartmann et al. (Hartmann et al., 1997). Briefly, the left bulla was exposed and opened, and the round window membrane was carefully removed. A human NUCLEUS 22 electrode (Cochlear Co., Basel) was implanted through the round window (Kral et al., 1998
). The NUCLEUS electrode consists of a silastic carrier of <0.65 mm diameter and 22 platinum rings of 0.35 mm width spaced 0.75 mm apart. By convention, the electrode rings are numbered 122 from the tip of the electrode. Due to the dimensions of the cat scala tympani, the NUCLEUS implant can only be inserted up to the tenth electrode ring.
Stimulation and Recording
The animals were stimulated with charge-balanced biphasic pulses of 200 µs duration per phase, applied in a bipolar stimulation mode using NUCLEUS electrode rings 2/3.
For recording, the skull was widely opened and the dura above the auditory cortex removed. Recordings were performed with glass microelectrodes filled with Ringer's solution (impedance Z < 6 M) or Elgiloy electrodes (Suzuki and Azuma, 1976
) (Z < 6 M
). The signal was amplified and band-pass filtered (10 Hz10 kHz) by a Tektronix 5A22N amplifier, averaged on a Mac II computer (50100 sweeps dependent on signal/noise ratio, repetition rate 2.1/s). As functional orientation in the auditory cortex in CDCs is not possible, anatomical landmarks were used for orientation. Field potentials were recorded in two parallel rostrocaudal sequences located between the dorsal end of the posterior ectosylvian sulcus (PES) and the anterior ectosylvian sulcus AES (Fig. 1a
). The distance between the individual recording positions in the rostrocaudal direction was 500 µm, resulting in 1420 recording positions.
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The cortex was penetrated at each recording position (Fig. 1a). The electrode was directed perpendicularly to the cortical surface using a stereotactic system. Field potentials were recorded every 150300 µm to a depth of 3600 µm. Electrode location was controlled by an ORIEL xyz positioning device (all three directions controlled with a precision of 1 µm). To avoid tangential tracks, no recordings were made near the sulci. Reproducibility of the recordings was verified by remeasuring the field potentials in several tracks during retraction of the electrode. With Elgiloy electrodes, iron deposits were made to verify both the track angle with respect to the cortical surface and the corresponding recording depths (1000, 2000 and 3000 µm depth, 510 µA d.c., 10 s). Sample tracks were marked with iontophoretic application of horseradish peroxidase (2 µA, 10 min) when using glass microelectrodes.
After the experiment, the animals were transcardially perfused [details are given in (Heid et al., 1998)]. The brains were cut on a freezing microtome in 40-µm-thick sections. The sections with iron deposits underwent the Prussian blue reaction (Brown and Tasaki, 1961
) and subsequent Nissl staining. In the horseradish peroxidase-marked tracks, the sections were stained with diaminobenzidene (LaVail and LaVail, 1972
; Mesulam, 1976
), followed by a subsequent Nissl staining. For determination of cortical layers, the angle of the track to the perpendicular direction in respect to cortical surface was defined as the deviation angle. Due to a non-zero deviation angle, the depth indicated during the recordings of field potentials by the xyz positioning device (penetration depths) may not equal the perpendicular distance of the recording positions from the pial surface (cortical depths). Therefore, histological track reconstruction was performed in sample tracks, the remaining tracks being reconstructed according to the recording position, the angle of the electrode in the stereotactic device and the stereotactical atlas of the cat brain (Reinoso-Suarez, 1961
). The one-dimensional shrinkage of the material (in the track direction) was calculated from the differences in penetration depths in vivo and those found in the histological reconstruction. The shrinkage was compensated for.
CSD Analysis
Using extracellular field potentials recorded in different cortical layers, the CSD analysis revealed gross synaptic currents within the investigated tissue at high spatial resolution. Far field effects, e.g. from the thalamus or neighbouring areas of the cortex, are eliminated. The one-dimensional CSD signal represents mainly synaptic currents from vertically oriented cells, predominantly from pyramidal cells (Müller-Preuss and Mitzdorf, 1984).
CSDs (Mitzdorf, 1985) were computed off-line from field potentials (Fig. 1b
; see Appendix). Each CSD curve was calculated from field potentials at three consecutive depths, resulting in 11 CSD curves in each track. For evaluation of CSD profiles, a region of interest (ROI) was defined (Fig. 1a
). This was located so that it contained the recording positions with largest Pa waves (first positive wave of the middle latency response). The ROI had dimensions of 1000 µm in the rostro-caudal and 1500 µm in the dorso-ventral direction and comprised 6 tracks in most animals.
An example of computed CSD curves is depicted in Figure 2. The curve shows the CSD over the first 50 ms after the stimulus. Sinks (inward currents with respect to the cellular membrane) are shown as positive deviations of the CSD curve and sources as negative deviations. The sinks of the CSDs correspond to gross synaptic currents, and were shaded in the figures and quantitatively evaluated. In Figure 2
, two large sinks can be differentiated, one starting at 7 ms latency and ending at 10 ms latency, the other starting at 18 ms latency and ending at 46 ms latency.
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To compare the overall synaptic activity in the cortices of individual CDCs to normal cats, CSDs calculated in the ROI were statistically evaluated. For this purpose, the sinks from all layers were pooled. For each animal the mean sink amplitude and the mean temporal integral were computed from the tracks located in the ROI. The normality of sink amplitude and temporal integral distributions were tested with the PearsonStephens test ( = 10%). The differences computed were tested for significance with the WilcoxonMannWhitney test (one-tailed,
= 5%) (Sachs, 1968
).
An example of the CSDs is given in Figure 3. The current source densities were computed from three consecutive depths. The CSD signal at 292 µm depth (layer II), for example, was thus computed from the field potentials recorded at 0 (surface), 292 (layer II) and 586 µm (layer III). This CSD signal reflects the gross synaptic currents at 292 µm (layer II). In a simplified view, each CSD sink has corresponding CSD sources at locations above and below, i.e. the large sink at depth 1171 µm is also reflected as a source at 878 µm and the very large source at 1463 µm depth.
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Results |
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The detailed analysis of the gross synaptic currents was performed for the ROI. First, the normal control data were determined. These were then compared with the data from CDCs. Finally, the results were statistically evaluated. Cortical layers were assigned to the penetration depths according to histological reconstruction of dye deposits (for details see Appendix).
Hearing Controls
Figure 3 illustrates a histologically reconstructed track located at the border of the ROI in a normal hearing cat. The cortical field potentials on the left show a positive Pa wave and a negative Na wave on the surface. The polarity of the first wave reverses at the depth of the cortex, so that a prominent negative wave is observed at depths between 586 and 878 µm (layers II and III) and below. A similar polarity reversal was observed with waves corresponding to Na at the pial surface. There were also differences in the fine structure of the field potentials between different cortical depths.
The activity of the cortical layers had a typical temporal sequence expressed as latency shifts in the current source densities. The sink with the shortest latency is found at depths of 1463 and 1756 µm in Figure 3, which corresponds to infragranular layer V. Subsequently, there is an activation of the cells at 878 µm depth, which is in layer IV. Afterwards, large amplitude and long duration sinks are found at depths of 586 (supragranular, layer III) and 1171 µm (infragranular, layer V). In addition, activation at depths of 2049 and 2635 µm is seen (infragranular, layer VI). Prolonged, low amplitude activation is found at depths of 292 (supragranular, layer II) and 2342 µm (infragranular, layer VI). With onset latencies of over 25 ms, activity is found at depths of 1463 and 1756 µm (infragranular, layer V).
Figure 4a illustrates a typical field potential track (left) recorded at the position where the Pa wave showed the largest amplitude at the surface (track located inside ROI). The corresponding CSD signals are shown on the right.
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Congenitally Deaf Cats
The CDC with the largest sink amplitudes was selected for comparison in Figure 4b. The track with the largest Pa amplitude at the surface is shown (located inside ROI). The field potentials and the CSDs differ from those of the hearing cat (Fig. 4a
).
Generally, the CDCs lacked the typical pattern of cortical activation seen in normal cats. The field potentials in the infragranular layers consisted of only small negative waves with ~10 ms latency. In CSDs, there was a substantial reduction of the sink amplitudes with longer latencies. The temporal sequence of synaptic activation of the cortical layers was different in CDCs (Fig. 4b, right):
Figure 5 shows the shortest sink latencies found in the ROI in all animals investigated. They are depicted for different penetration depths. The normal cats had almost simultaneous activation at all depths, whereas the CDCs showed greater variation and generally longer latencies. Statistical significance is indicated in the figure by asterisks (two-tailed t-test,
= 5%). Significant differences were found for penetration depths of 600 (layer III), 2100, 2400 and 2700 µm (layers V/VI). The shortest sink latencies were also longer in CDCs at depths of 15001800 µm (layer V). Because of large standard deviations this difference did not reach statistical significance. As will be shown below, the sinks in infragranular layers with long latencies had small amplitudes.
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The mean sink amplitudes, mean temporal integrals of the sinks, maximum values of the sink amplitudes and maximum values of the temporal integrals are shown in Table 1.
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Sink Amplitudes.
The difference in sink amplitudes in the control cats was also not significant (means 1389 and 1340 µV/mm2). Again, the data were therefore pooled and compared with those of the CDCs. All CDCs had significantly smaller sink amplitudes (means from 578 to 1117 µV/mm2) than normal cats (WilcoxonMannWhitney test at = 5%). Of the sink amplitudes, the largest ones were determined for each animal (maximum sink amplitudes). All CDCs had smaller maximum sink amplitudes.
Next, the sink amplitude distribution with respect to cortical layers was investigated. Individual recording tracks represent signals from a topologically restricted column of cortical cells. To minimize the influence of the exact location of individual tracks within the auditory cortex, sink amplitudes were pooled for all tracks within the ROI and presented together for each cat (Fig. 6). This comprised at least six microelectrode tracks in each animal (Fig. 1
). For each cortical layer, the sink amplitudes from all six tracks were pooled and depicted at the corresponding latency. Track position information inside the ROI was therefore lost in this presentation. The individual sink amplitudes, as shown in Figure 6
in the layer-latency plane, could have been computed in any of the six tracks in the ROI. Layer specificity, latency and amplitude were preserved.
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Influence of Anaesthetics
To rule out the effect of the type of anaesthetic in the activation of the auditory cortex in CDC, two different anaesthetics were used, namely, isoflurane and N2O in WK6527 and WK9576, and ketamine in all remaining animals. In all animals, the identical criteria of anaesthesia depth were applied (Kral et al., 1999).
The pattern of cortical activation as revealed by CSD analyses did not show any substantial differences. When comparing animals of similar age (e.g. WK6527 to WK9582, and WK9576 to WK9568; see also Fig. 6), the sink amplitudes and sink areas were not significantly different (WilcoxonMannWhitney,
= 5%).
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Discussion |
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These results show substantial deficits in the activity of a naive auditory cortex in response to stimulation of the auditory nerve. Similarly, binocular congenital deprivation leads to a decrease in visually evoked responses of the visual cortical areas, primarily the striate cortex (Yaka et al., 1999). Stryker and Harris showed that a naive visual cortex, following chronic abolition of all afferent neural activity by TTX, lacks the normal segregation of thalamocortical afferents from each eye (Stryker and Harris, 1986
). Dark-rearing, which is known to leave spontaneous activity intact, alters the formation of ocular dominance, albeit to a lesser extent (Cynader et al., 1976
; Leventhal and Hirsch, 1980
; Swindale, 1988
). It reduces the percentage of orientation- and direction-selective cells (Imbert and Buisseret, 1975
; Buisseret and Imbert, 1976
). Dark-rearing also leads to a decrease in the number of dendrites in the visual cortex (Reid and Daw, 1995
). Similarly, the number and length of dendrites in the auditory cortex of CDCs are also significantly reduced (Wurth et al., 1999
). In the light of this information, congenital deprivation can be expected to lead to a functionally deficient auditory cortex.
Methodological Considerations
The recordings were performed in CDCs at positions that correspond to the field AI in hearing cats. The position in AI was additionally verified by the short latencies of Pa waves [compare (Hartmann et al., 1997)]. The partitioning of auditory cortex and the cytoarchitectonic characteristics of the different compartments are unknown in CDCs. Cell morphology is different in the CDC auditory cortex (Wurth et al., 1999
). As a consequence, a reliable identification of AI based on cytoarchitectonics is not possible at present. Further evidence for a recording position in AI is provided by the fact that a rudimentary cochleotopy has been demonstrated in this area of the auditory cortex in CDCs (Hartmann et al., 1997
). According to these data, the intracochlear stimulation site used represents the best stimulus' for the cortical position evaluated. The stimulating electrodes 2/3 (see Materials and Methods) of the NUCLEUS device lie at a position equivalent to characteristic frequencies of 811 kHz in the cochlea (Hartmann et al., 1997
). In normal hearing cats, the projection of this cochlear region is located ~2 mm rostral to the posterior ectosylvian sulcus (Merzenich et al., 1975
; Reale and Imig, 1980
; Phillips and Irvine, 1981
). In this study, maximal field potential amplitudes were recorded at approximately this position. There was always a single amplitude maximum with an amplitude decrease in both rostral and dorsal directions. Therefore, the cortical representation of the cochlear portion stimulated is located in the area evaluated (ROI). For the sake of standardization, thresholds of the middle-latency responses were initially determined at a point 1 mm rostral to the dorsal end of the PES. Previous studies have shown that there are no pronounced differences in threshold at this region of AI, although the thresholds increase in the more rostral parts of AI (Hartmann et al., 1997
). Final stimulation currents were then fixed at 10 dB above this threshold. With this intensity, a plateau in the electrically evoked amplitudeintensity function of field potentials is safely reached. Thus, a small underestimation of threshold would not cause substantial differences in cortical activation. It should be mentioned that cortical single-units also possess a dynamic range of 10 dB with pulsatile electrical stimulation (Hartmann et al., 1997
).
The microelectrode possesses a distance sensitivity of ~30 µm (Sugimoto et al., 1997). Recording steps of 300 µm during micro- electrode tracks correspond to previous studies in the auditory cortex (Müller-Preuss and Mitzdorf, 1984
). The recordings in the same track were reproducible, as verified by recording during retraction of the electrode. This was done on four sample tracks and no substantial differences could be observed.
To further investigate the reproducibility of the cortical activation pattern under different anaesthesia, isoflurane in combination with N2O was used in two CDCs. The pharmacological effect of ketamine and isoflurane is mainly on the excitatory synaptic transmission (Zuo et al., 1996; Newcomer et al., 1999
). Isoflurane also acts on inhibitory synaptic transmission (Irifune et al., 1997
; Wakasugi et al., 1999
). Using the same criteria of anaesthesia depth (Kral et al., 1999
), the two anaesthetics used did not lead to significant differences in the field potentials and gross synaptic currents.
Synaptic Activity
Normal Hearing Acutely Deafened Cats (Controls)
The pattern of gross excitatory synaptic currents in normal hearing acutely deafened cats corresponds well to the data from acoustically stimulated squirrel monkey auditory cortex (Müller-Preuss and Mitzdorf, 1984) and cat visual cortex (Mitzdorf, 1985
; Friauf and Shatz, 1991
). Fishman et al. report very similar patterns of excitation (as revealed by CSD analysis) in the auditory cortex of the macaque monkey, although no depth or cortical layer verification was performed (Fishman et al., 1998
).
The present results from normal cats demonstrate the typical temporal sequence of cortical layer activation in the primary auditory cortex. The shortest latency was demonstrated in gross synaptic currents in infragranular layers. Layers I, III, IV, V and VI are known to receive direct thalamocortical connections (Mitani et al., 1985; Prieto et al., 1994
). Therefore, it is assumed that the short-latency gross synaptic currents in the infragranular layers reflect this direct thalamocortical input. Layer IV is the principal input layer of the cortex with most thalamocortical synapses (Niimi and Naito, 1974
). This layer contains stellate cells, and it has been assumed that most synapses are formed with this cell type. Synapses to stellate cells would explain the smaller amplitudes of the sinks. Stellate cells have no preferential (vertical) orientation and a rather small size. Thus the spatial resolution of the CSD method (300 µm) may not suffice to consistently reveal all sinks and sources from these cells. Consequently, the infragranular sinks, which are more reproducible, may appear to show shorter latency over the ROI than sinks from layer IV. Additionally, our latencies are given as peak latencies. A closer inspection of Figure 4
[which fits data from e.g. (Müller-Preuss and Mitzdorf, 1984
; Friauf and Shatz, 1991
)] reveals similar onset latencies of the earliest sinks in layer IV and V/VI in the hearing cat, but a considerably shorter peak latency in layer V/VI.
Layer-specific latency studies are based on multi-unit recordings. These have a spatial resolution of tenths of micrometers, which is finer than the CSD method (steps of the order of hundreds of micrometers; in the present study 150300 µm). The present study investigates synaptic currents which may also be subthreshold. Differences can therefore be expected, although some multi-unit studies also demonstrate their smallest latencies in layer VI (Sugimoto et al., 1997).
A possible explanation of the temporal pattern of gross synaptic currents observed in normal cats (examples in Figs 3 and 4a) is presented in a model of cortical interconnections shown schematically in Figure 7a
. It is based on latency differences between gross synaptic currents in different cortical layers. The assumption was that gross synaptic currents in one layer are caused by direct functional connections from layers which were activated <2 ms before. This model is compatible with the schemes published earlier according to anatomical and functional connections (Mitani et al., 1985
; Aitkin, 1990
; Prieto et al., 1994
). According to the present results, a coactivation of layers III, IV, V and VI by thalamocortical afferents can be expected first (the CSD method does not allow layer I to be investigated). This is in agreement with Mitani et al. (Mitani et al., 1985), who found coactivation of layers I, III, IV, V and VI. Prieto et al. (Prieto et al., 1994
) also describe thalamocortical connections in layers I, III, IV and VI. According to the CSD analysis, an excitation of cells in supragranular layers follows this input activity. The activity of supragranular layers is then relayed to the cells in the infragranular layers. Thereafter, there appears to be a rather complicated activation of both supra- and infragranular layers. This is assumed to be caused by intracortical circuits (both vertical and tangential). Tangential intracortical connections are very important in the processing of sensory stimuli and might be crucial for complex analyses (Winguth and Winer, 1986
; Maunsell and Newsome, 1987
; Singer, 1995
; Katz and Shatz, 1996
). An alternative explanation of the longer- latency currents might be that cortical neurons show intrinsic oscillatory responses (Gray and McCormick, 1996
). The third possibility is an ongoing input from the thalamus in the time window investigated here (the first 50 ms post-stimulus). Nevertheless, there are several observations that indicate a simple onset activation of cortical networks from the thalamus in electrically stimulated normal cats. Single and multi-unit activity exhibits only a simple onset peak (sometimes bimodal) in the first 50 ms of the post-stimulus time histogram after electrical pulsatile stimulation in the cochlea [cat cortex (Raggio and Schreiner, 1994
; Popelar et al., 1995
; Schreiner and Raggio, 1996
; Hartmann et al., 1997
); inferior colliculus in cats and guinea pigs (Snyder et al., 1995
; Vischer et al., 1997
)]. The fourth possibility is that longer-latency currents represent rebound phenomena (Eggermont, 1992
).
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In CDCs, CSDs show a different pattern of activation of the primary auditory cortex (Fig. 7b). Thalamic input is restricted to layers IV and V/VI. Layer IV gross synaptic currents show a loss in fine structure of the sinks in comparison with normal hearing cats. This might indicate functional deficits of the afferent auditory pathway (e.g. in thalamocortical afferents) as well as some changes in the layer IV neurons themselves.
The activity from layer IV is transferred to the supragranular layers. Activation of infragranular layers at longer latencies, which is believed to be caused by activity in supragranular layers (Fig. 7a) (Mitani et al., 1985
; Prieto et al., 1994
), is substantially reduced in CDCs. The infragranular layers are the output layers of the cortex. They provide input to other cortical areas and are the origin of efferent connections to the thalamus. Loss of activity in these layers indicates that the activity in the naive cortex is not propagated to the normal targets. Layers V and VI are the major sources of corticothalamic projection (Andersen et al., 1980
; Wong and Kelly, 1981
; Mitani and Shimokouchi, 1985
). Thalamo-cortico-thalamic loops (Steriade, 1997
; de Venecia et al., 1998
) are therefore probably not functional in CDCs. The normal centrifugal projection to the inferior colliculus, which originates in layer V (Andersen et al., 1980
, Mitani et al., 1983
), is probably affected as well. Commissural fibres to the contralateral auditory cortex might be less affected by congenital deprivation, as these fibres originate not only in layer VI but also in layer III (Imig and Brugge, 1978
; Wong and Kelly, 1981
). The major source of output to AII are layers III and V in normal AI (Winguth and Winer, 1986
). As some activity is preserved in layer III in CDCs, AII (if functionally present) might receive inputs.
The reasons for the insufficiencies observed in CDC primary auditory cortex are not known. Three possible hypotheses are:
At present there is no published material available to support either of these hypotheses. Equipping the CDCs with a cochlear implant at an early age replaces auditory experience and indicates reversibility of the described changes (Klinke et al., 1999). The study has demonstrated that chronic electrical stimulation with biologically relevant stimuli leads to:
Whether there is a critical period outside of which such maturation cannot be achieved is under study. Apart from sink amplitudes, the present data demonstrate similar quantitative measures of synaptic currents in the youngest CDCs to hearing cats. In older CDCs there is a decreasing trend with age (Table 1). This finding may represent an indication of a sensitive period.
The changes described in the present paper could also be based on changes in the function of the afferent auditory pathway as well as changes in the auditory cortex. Dramatic effects of unilateral cochlear ablation have been demonstrated in the brainstem of Mongolian gerbils (Kitzes et al., 1995). Changes in the afferent auditory pathway certainly will affect the input to the auditory cortex, and thus also influence the evoked cortical activity.
Several histological studies have been undertaken on CDCs. Larsen and Kirchhoff found that the end bulbs of Held in adult CDCs resemble immature synapses of young kittens (Larsen and Kirchhoff, 1992). They demonstrated a decrease in the cross-sectional area of the soma of large spherical cells in the CDCs, accompanied by a dramatic increase in both the pre- and postsynaptic membranes. CDCs have fewer and thinner branches of the end bulbs, which also have fewer varicosities and fewer terminal swellings (Ryugo et al., 1997
, 1998
). There is a reduction of presynaptic vesicle density. Postsynaptic densities are thicker and expanded. Heid (Heid, 1998
) showed a significant reduction in somatic areas of neurons in the cochlear nucleus, superior olivary complex and lateral lemniscus in adult CDCs [see also (Saada et al., 1996
)]. On the other hand, CDCs have preserved nucleotopic projections in the brainstem (Heid et al., 1997
). Similar results have also been presented for deafened ferrets (Moore, 1990
). Hardie et al. demonstrated morphological changes in the inferior colliculus of neonatally bilaterally deafened cats (Hardie et al., 1998
). There was a significant reduction in number of synapses. No decrease of neuronal counts has been reported in the brainstem of auditory deprived cats. Cochlear ablation leads to such effects in, for example, birds (Born and Rubel, 1985
).
In spite of these morphological data, only limited functional deficits could be demonstrated in the central auditory system of CDCs and neonatally deafened cats. In studies in the inferior colliculus of neonatally deafened cats, Snyder et al. (Snyder et al., 1990, 1991
, 1995
) showed that
Hartmann et al. (Hartmann et al., 1996) reported similar results for the inferior colliculus of CDCs; furthermore, they recorded multi-units in the auditory cortex of CDCs (Hartmann et al., 1997
). Their post-stimulus time histograms do not exhibit substantial differences from electrically stimulated normal cats. A rudimentary cochleotopy has also been demonstrated (Hartmann et al., 1997
). Hardie and Shepherd demonstrated a significant increase in the threshold of electrically evoked brainstem responses in neonatally deafened animals (Hardie and Shepherd, 1999
). A more pronounced increase in latency and threshold of wave IV has also been described. Nevertheless, these findings might relate to the loss of auditory nerve fibres and their demyelination, which is a consequence of application of ototoxic drugs (Hardie and Shepherd, 1999
). On the other hand, a weakening of excitatory synapses as a consequence of congenital deprivation has been demonstrated in brain slices of gerbils after neonatal cochlear ablation (Kotak and Sanes, 1997
).
Thus, with the exception of an increased stimulation threshold, the functional thalamocortical input to the auditory cortex of CDCs seems relatively unaffected. The effect of such a possible decreased excitability was balanced in this study by using a relative criterion for stimulation current. The stimulation intensity was related to the threshold of cortical field potentials in each cat (10 dB over individual threshold). The differences in response latencies, as observed in the brainstem, could have influenced the first latencies in the cortical sinks, but an unequal effect on latency in different layers, as shown in Figure 5, cannot be explained simply by increased latencies in the brainstem. The differences observed in this study are thus most probably of cortical origin. For the same reason, the dramatic decreases in amplitude of the sinks are most probably of cortical origin. Last but not least, the substantial differences in the temporal sequence of cortical layer activation between normal cats and CDCs cannot be explained by an overall decrease of responsiveness or change in cortical input. The same arguments can be applied to the reduction of synaptic currents with longer latencies and in infragranular layers.
A functionally deficient primary auditory cortex, as observed in the present study, should also show morphological differences to normal cortices. Indeed, morphological data from CDCs show a significant reduction in the number of primary dendrites in pyramidal cells (Wurth et al., 1999). A reduction in the span of dendritic trees was also observed in the cortex. This would imply a reduction in the number of synapses, which in turn should diminish synaptic activity, as was shown in this study.
The question of what happens to the primary auditory cortex in congenital deafness remains. It has been suggested that it is recruited by the visual system in the CDC (Rebillard et al., 1977, 1980
). This finding could not be reproduced in our laboratory (Hartmann et al., 1997
). The present study on synaptic currents demonstrates functional impairments in the interlayer connections of the auditory cortex. This supports the hypothesis that the auditory cortex, at least the region which corresponds to AI in hearing cats, is deprived of input. Furthermore, the morphological data on the cortical neurons in CDCs with a significant reduction of the number of primary dendrites support this view. If the cortex was recruited by some other modality, there should be no pronounced deficits observable. Nevertheless, the possibility that the recruiting system might activate the auditory cortex in a manner different to the normal auditory input remains open. This could lead to functional impairments in response to auditory input and to morphological differences in some neuronal populations. Nevertheless, recent data on the visual system also support our view. In the naive visual system, no substantial recruitment of area 17 by the auditory system could be found (Yaka et al., 1999
).
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Address correspondence to A. Kral, Physiologisches Institut III, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. Email: kral{at}em.uni-frankfurt.de.
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Track Reconstruction
The accuracy of the assignment of cortical layers to penetration depths was ensured by histological track reconstruction. The deviation angle (Fig. 3) in the histologically reconstructed tracks was 014°. The maximal possible deviation angle with the given adjustment of the stereotactical microelectrode holder was 36° according to the cat stereotactical brain atlas.
The accuracy of cortical layer assignment for given penetration depths is given by the span between the penetration depth (0° deviation) and cortical depths for the maximum possible deviation angle of 36°.
The assignment of layer IV was found to be accurate in the recorded area (Fig. 1a). Layer IV was found to extend from a cortical depth between 730 (minimum from nine positions in AI) and 1040 µm (maximum from nine positions in AI) in the histological preparations of both hearing and deaf cats. After correction for 11% tissue shrinkage, this corresponds to cortical depths of 8101154 µm, which in turn corresponds to penetration depths of 9001200 µm. Furthermore, all iron deposits at track depth 1000 µm were found in layer IV. The positions of layers II and III had to be extrapolated. As the track angle does not result in large differences in cortical depth for these small penetration depths, their assignment can be considered to be accurate. The depth error increases with increasing penetration depth. The assignment of deeper layers (infragranular layers V and VI) therefore becomes difficult for the unreconstructed tracks. The border of layers V and VI also depends on the distance from the sulci. To minimize errors in layer assignment, the differentiation to layers V and VI was not performed, and signals from these layers are given as layer V/VI in the text.
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References |
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Andersen RA, Knight PL, Merzenich MM (1980) The thalamocortical and corticothalamic connections of AI, AII and anterior auditory field (AAF) in the cat: evidence for largely segregated systems. J Comp Neurol 194:663701.[ISI][Medline]
Blakemore C (1978) Maturation and modification in the developing visual system. In: Handbook of sensory physiology, vol. III. Perception (Held R, Leibowitz HW, Teuber HL, eds), pp. 377436. Berlin: Springer-Verlag.
Born DE, Rubel EW (1985) Afferent influences on brain stem auditory nuclei of the chicken: neuron number and size following cochlea removal. J Comp Neurol 231:435445.[ISI][Medline]
Brown KT, Tasaki K (1961) Localization of electrical activity in the cat retina by an electrode marking method. J Physiol (Lond) 158:281295.[ISI]
Buisseret P, Imbert M (1976) Visual cortical cells: their developmental properties in normal and dark-reared kittens. J Physiol 255:511525.[Abstract]
Busby PA, Tong YC, Clark GM (1992) Psychophysical studies using multi- electrode cochlear implant in patients who were deafened early in life. Audiology 31:95111.[ISI][Medline]
Chugani HT, Müller RA, Chugani DC (1996) Functional brain reorganization in children. Brain Dev 18:347356.[ISI][Medline]
Cynader M, Berman N, Hein A (1976) Recovery of function in cat visual cortex following prolonged deprivation. Exp Brain Res 25:139156.[ISI][Medline]
de Venecia RK, Smelser CB, McMullen NT (1998) Parvaglobulin is expressed in a reciprocical circuit linking the medial geniculate body and auditory neocortex in the rabbit. J Comp Neurol 400:349362.[ISI][Medline]
Eddington DK, Dobelle WH, Brackmann DE, Mladejovsky MG, Parkin JL (1978) Auditory prostheses research with multiple channel intra- cochlear stimulation in man. Ann Otol Rhinol Laryngol Suppl 53:539.
Eggermont JJ (1992) Stimulus induced and spontaneous rhythmic firing of single units in cat primary auditory cortex. Hear Res 61:111.[ISI][Medline]
Fishman YI, Reser DH, Arezzo JC, Steinschneider M (1998) Pitch v. spectral encoding of harmonic complex tones in primary auditory cortex of the awake monkey. Brain Res 786:1830.[ISI][Medline]
Friauf E, Shatz CJ (1991) Changing pattern of synaptic input to subplate and cortical plate during development of visual cortex. J Neurophysiol 66:20592071.
Fryauf-Bertschy H, Tyler RS, Kelsay DMR, Gantz BJ, Woodworth GG (1997) Cochlear implant use by prelingually deafened children: the influences of age at implant and length of device use. J Speech Lang Hear Res 40:183199.[ISI][Medline]
Gray CM, McCormick DA (1996) Chattering cells: superficial pyramidal neurons contributing to the generation of synchronous oscillations in the visual cortex. Science 274:109113.
Hardie NA, Shepherd RK (1999) Sensorineural hearing loss during development: morphological and physiological response of the cochlea and auditory brainstem. Hear Res 128:147165.[ISI][Medline]
Hardie NA, Martsi-McClintock A, Aitkin L, Shepherd RK (1998) Neonatal sensorineural hearing loss affects synaptic density in the auditory midbrain. NeuroReport 9:20192022.[ISI][Medline]
Harrison RV, Nagasawa A, Smith DW, Stanton S, Mount RJ (1991) Reorganization of auditory cortex after neonatal high frequency hearing loss. Hear Res 54:1119.[ISI][Medline]
Hartmann R, Topp G, Klinke R (1984) Discharge patterns of cat primary auditory fibers with electrical stimulation of the cochlea. Hear Res 13:4762.[ISI][Medline]
Hartmann R, Heid S, Klinke R (1996) Neuronal activity in the auditory cortex and inferior colliculus of congenitally deaf white cats evoked by electrical cochlear stimulation. In: Proceedings of the 24th Göttingen Neurobiology Conference (Elsner N, Schnitzler H-U, eds), vol. II, p. 460. Stuttgart: Thieme Verlag.
Hartmann R, Shepherd RK, Heid S, Klinke R (1997) Response of the primary auditory cortex to electrical stimulation of the auditory nerve in the congenitally deaf white cat. Hear Res 112:115133.[ISI][Medline]
Heid S (1998) Morphometrische Befunde am peripheren und zentralen auditorischen System der kongenital gehörlosen Katze. PhD Thesis, J.W. Goethe University, Frankfurt am Main.
Heid S, Jähn-Siebert TK, Klinke R, Hartmann R, Langner G (1997) Afferent projection pattern in the auditory brainstem in normal cats and congenitally deaf white cats. Hear Res 110:191199.[ISI][Medline]
Heid S, Hartmann R, Klinke R (1998) A model for prelingual deafness, the congenitally deaf white catpopulation statistics and degenerative changes. Hear Res 115:101112.[ISI][Medline]
Hubel DH, Wiesel TN (1970) The period of susceptibility to the physiological effects of unilateral eye closure in kittens. J Physiol (Lond) 206:419436.[ISI][Medline]
Imbert M, Buisseret P (1975) Receptive field characteristics and plastic properties of visual cortical cells in kittens reared with or without visual experience. Exp Brain Res 22:2536.[ISI][Medline]
Imig TJ, Brugge JF (1978) Sources and terminations of callosal axons related to binaural and frequency maps in primary auditory cortex of the cat. J Comp Neurol 182:637660.[ISI][Medline]
Irifune M, Sato T, Nishikawa T, Masuyama T, Nomoto M, Fukuda T, Kawahara M (1997) Hyperlocomotion during recorvery from isoflurane anesthesia is associated with increased dopamine turnover in the nucleus accumbens and striatum in mice. Anesthesiology 86: 464475.[ISI][Medline]
Juliano SL (1998) Mapping the sensory mosaic. Science 279:16531654.
Katz LC, Shatz CJ (1996) Synaptic activity and the construction of cortical circuits. Science 274:11331138.
Kilgard MP, Merzenich MM (1998) Cortical map reorganization enabled by nucleus basalis activity. Science 279:17141718.
Kitzes LM, Kageyama GH, Semple MN, Kil J (1995) Development of ectopic projections from the ventral cochlear nucleus to the superior olivary complex induced by neonatal ablation of the contralateral cochlea. J Comp Neurol 353:341363.[ISI][Medline]
Klinke R, Kral A, Heid S, Tillein J, Hartmann R (1999) Recruitment of the auditory cortex in congenitally deaf cats by long-term electro- stimulation through a cochlear implant. Science 285:17291733.
Kotak VC, Sanes DH (1997) Deafferentation weakens excitatory synapses in the developing central auditory system. Eur J Neurosci 9: 23402347.[ISI][Medline]
Kral A, Hartmann R, Mortazavi D, Klinke R (1998) Spatial resolution of cochlear implants: the electrical field and excitation of auditory afferents. Hear Res 121:1128.[ISI][Medline]
Kral A, Tillein J, Hartmann R, Klinke R (1999) Monitoring of anaesthesia in neurophysiological experiments. NeuroReport 10:781787.[ISI][Medline]
Larsen SA, Kirchhoff TM (1992) Anatomical evidence of synaptic plasticity in the cochlear nuclei of white-deaf cats. Exp Neurol 115:151157.[ISI][Medline]
LaVail JH, LaVail MM (1972) Retrograde axonal transport in the central nervous system. Science 176:14161417.[ISI][Medline]
Leake-Jones PA, Vivion MC, O'Reilly BF, Merzenich MM (1982) Deaf animal models for studies of a multichannel cochlear prosthesis. Hear Res 8:225246.[ISI][Medline]
Leventhal AG, Hirsch HB (1980) Receptive field properties of different classes of neurons in visual cortex of normal and dark-reared cats. J Neurophysiol 43:11111132.
Maunsell JHR, Newsome WT (1987) Visual processing in monkey extrastriate cortex. Annu Rev Neurosci 10:363401.[ISI][Medline]
McMullen NT, Goldberger B, Suter CM, Glaser EM (1988) Neonatal deafening alters nonpyramidal dendrite orientation in auditory cortex: a computer microscopic study. J Comp Neurol 267:92106.[ISI][Medline]
Merzenich MM, Knight PL, Roth GL (1975) Representation of cochlea within primary auditory cortex of the cat. J Neurophysiol 38: 231249.
Mesulam MM (1976) The blue reaction product in horseradish peroxidase neurohistochemistry: incubation parameters and visibility. J Histochem Cytochem 24:12731280.[Abstract]
Mitani A, Shimokouchi M (1985) Neuronal connections in the primary auditory cortex: an electrophysiological study in the cat. J Comp Neurol 235:417429.[ISI][Medline]
Mitani A, Shimokouchi Mnomura S (1983) Effects of stimulation of the primary auditory cortex upon colliculogeniculate neurons in the inferior colliculus of the cat. Neurosci Lett 42:185189.[ISI][Medline]
Mitani A, Shimokouchi M, Itoh K, Nomura S, Kudo M, Mizuno N (1985) Morphology and laminar organization of electrophysiologically identified neurons in the primary auditory cortex in the cat. J Comp Neurol 235:430447.[ISI][Medline]
Mitzdorf U (1985) Current source density method and application in cat cerebral cortex: investigations of evoked potentials and EEG phenomena. Physiol Rev 65:37100.
Moore D (1990) Auditory brain stem of the ferretbilateral cochlear lesions in infancy do not affect the number of neurons projecting from the cochlear nucleus to the inferior colliculus. Dev Brain Res 54: 125130.[ISI][Medline]
Moore JK, Niparko JK, Perazzo LM, Miller MR, Linthicum FH (1997) Effect of adult-onset deafness on the human central auditory system. Ann Otol Rhinol Laryngol 106:385390.[ISI][Medline]
Müller-Preuss P, Mitzdorf U (1984) Functional anatomy of the inferior colliculus and the auditory cortex: current source density analyses of click evoked potentials. Hear Res 16:133142.[ISI][Medline]
Neville HJ, Lawson D (1987) Attention and peripheral visual space in a movement detection task. III. Separate effects of auditory deprivation and acquisition of a visual language. Brain Res 405:284294.[ISI][Medline]
Newcomer JW, Farber NB, Jevtovic-Todorovic V, Selke G, Melson AK, Hershey T, Craft S, Olney JW (1999) Ketamine-induced NMDA receptor hypofunction as a model of memeory impairment and püsychosis. Neuropsychopharmacology 20:106118.[ISI][Medline]
Nicholson C, Freeman JA (1975) Theory of current source density analysis and determination of conductivity tensor for an auran cerebellum. J Neurophysiol 38:356368.
Niimi K, Naito F (1974) Cortical projections of the medial geniculate body of the cat. Exp Brain Res 19:326342.[ISI][Medline]
Niparko JK, Finger PA (1997) Cochlear nucleus cell size changes in the dalmatian: model of congenital deafness. Otolaryngol Head Neck Surg 117:229235.[ISI][Medline]
Nishimura H, Hashikawa K, Doi K, Iwaki T, Watanabe Y, Kusuoka H, Nishimura T, Kubo T (1999) Sign language heard in the auditory cortex. Nature 397:116.[ISI][Medline]
Phillips DP, Irvine DRF (1981) Responses of single neurons in physiologically defined primary auditory cortex (AI) of the cat: frequency tuning and responses to intensity. J Neurophysiol 45: 4858.
Ponton CW, Don M, Eggermont JJ, Waring MD, Kwong B, Masuda A (1996) Auditory system plasticity after long periods of complete deafness. NeuroReport 8:6165.[ISI][Medline]
Popelar J, Hartmann R, Syka J, Klinke R (1995) Middle latency responses to acoustical and electrical stimulation of the cochlea in the cats. Hear Res 92:6377.[ISI][Medline]
Prieto JJ, Peterson BA, Winer JA (1994) Morphology and spatial distribution of GABAergic neurons in cat primary auditory cortex. J Comp Neurol 344:349382.[ISI][Medline]
Raggio MW, Schreiner CE (1994) Neural responses cat primary auditory cortex to electrical stimulation. I. Intensity dependence of firing rate and response latency. J Neurophysiol 72:23342359.
Rauschecker J (1991) Mechanisms of visual plasticity: Hebb synapses, NMDA receptors and beyond. Physiol Rev 71:587615.
Reale RA, Imig TJ (1980) Tonotopic organisation in auditory cortex of the cat. J Comp Neurol 192:265291.[ISI][Medline]
Rebillard G, Carlier E, Rebillard M, Pujol R (1977) Enhancement of visual responses on the primary auditory cortex of the cat after an early destruction of cochlear receptors. Brain Res 129:162164.[ISI][Medline]
Rebillard G, Rebillard M, Pujol R (1980) Factors affecting the recording of visual-evoked potentials from the deaf cat primary auditory cortex (A1). Brain Res 188:252254.[ISI][Medline]
Reid SNM, Daw NW (1995) Dark-rearing changes dendritic microtubule- associated protein 2 (MAP2) but not subplate neurons in cat visual cortex. J Comp Neurol 359:3847.[ISI][Medline]
Reinoso-Suarez F (1961) Topographischer Hirnatlas der Katze. Darmstadt: E. Merck AG.
Robertson RT (1987) A morphometric role for transiently expressed acetylcholine esterase activity in the developing thalamocortical systems? Neurosci Lett 75:259264.[ISI][Medline]
Robertson RT, Motamond F, Kageyama GH, Gallardo KA (1991) Primary auditory cortex in the rat: transient expression of acetylcholine esterase activity in developing geniculocortical projection. Devl Brain Res 58:8195.[Medline]
Ryugo DK, Pongstaporn T, Huchton DM, Niparko JK (1997) Ultra- structural analysis of primary endings in deaf white cats: morphologic alterations in end bulbs of Held. J Comp Neurol 385:230244.[ISI][Medline]
Ryugo DK, Rosenbaum BT, Kim PJ, Niparko JK, Saada AA (1998) Single unit recordings in the auditory nerve of the congenitally deaf white cats: morphological correlates in the cochlea and the cochlear nucleus. J Comp Neurol 397:532548.[ISI][Medline]
Saada AA, Niparko JK, Ryugo DK (1996) Morphological changes in the cochlear nucleus of congenitally deaf white cats. Brain Res 736:315328.[ISI][Medline]
Sachs L (1968) Statistische Auswertungsmethoden. Berlin: Springer- Verlag.
Schreiner CE, Raggio MW (1996) Neural responses in cat primary auditory cortex to electrical stimulation. II. Repetition rate coding. J Neurophysiol 75:12831300.
Singer W (1995) Development and plasticity of cortical processing architectures. Science 270:758764.[Abstract]
Skuse DH (1993) Extreme deprivation in early childhood. In: Language development in exceptional circumstances (Bishop D, Mogford K, eds), pp. 2946. Hove: Lawrence Erlbaum.
Snyder RL, Rebscher SJ, Cao K, Leake PA, Kelly K (1990) Chronic intracochlear electrical stimulation in the neonatally deafened cat. I. Expansion of central representation. Hear Res 50:734.[ISI][Medline]
Snyder RL, Rebscher SJ, Leake PA., Kelly K, Cao K (1991) Chronic intracochlear electrical stimulation in the neonatally deafened cat. II. Temporal properties of neurons in the inferior colliculus. Hear Res 56:246264.[ISI][Medline]
Snyder R, Leake P, Rebscher S, Beitel R (1995) Temporal resolution of neurons in cat inferior colliculus to intracochlear electrical stimulation: effects of neonatal deafening and chronic stimulation. J Neurophysiol 73:449467.
Steriade M (1997) Synchronized activities of coupled oscillators in the cerebral cortex and thalamus at different levels of vigilance. Cereb Cortex 7:583604.[Abstract]
Stryker MP, Harris WA (1986) Binocular impuls blockade prevents the formation of ocular dominance columns in cat visual cortex. J Neurosci 6:21172133.[Abstract]
Sugimoto S, Sakurada M, Horikawa J, Taniguchi I (1997) The columnar and layer-specific response properties of neurons in the primary auditory cortex of Mongolian gerbils. Hear Res 112:175185.[ISI][Medline]
Suzuki H, Azuma M (1976) A glass-insulated Elgiloy microelectrode for recording unit activity in chronic monkey experiments. Electro- enceph Clin Neurophysiol 41:9395.[ISI][Medline]
Swindale NV (1988) Role of visual experience in promoting segregation of eye dominance patches in visual cortex of the cat. J Comp Neurol 267:472488.[ISI][Medline]
Vischer MW, Bajo WM, Zhang JS, Calciati E, Haenggeli CA, Rouiller EM (1997) Single unit activity in the inferior colliculus of the rat elicited by electrical stimulation of the cochlea. Audiology 36:202227.[ISI][Medline]
Wakasugi M, Hirota K, Roth SH, Ito Y (1999) The effects of general anaesthetics on excitatory and inhibitory synaptic transmission in area CA1 of the rat hippocampus in vitro. Anesthesiol Analg 88: 676680.
Wakita M, Watanabe S (1997) Compensatory plasticity following neonatal lesion of the auditory cortex. Biomed Res 18(suppl. 1):7989.
Weinberger N (1998) Tuning the brain by learning and by stimulation of the nucleus basalis. Trends Cogn Sci 2:271273.[ISI]
Winguth SD, Winer JA (1986) Corticocortical connections of cat primary auditory cortex (AI): laminar organization and identification of supragranular neurons projecting to area AII. J Comp Neurol 248:3656.[ISI][Medline]
Wong D, Kelly JP (1981) Differentially projecting cells in individual layers of the auditory cortex: a double labeling study. Brain Res 230:362366.[ISI][Medline]
Wurth NN, Heid S, Kral A, Klinke R (1999) Morphology of neurons in the primary auditory cortex (AI) in normal and congenitally deaf catsa study of DiI labelled cells. Göttingen Neurobiol Rep 318.
Xu SA, Shepherd RK, Chen Y, Clark GM (1993) Profound hearing loss in the cat following the single co-administration of kanamycin and ethacrynic acid. Hear Res 70:205215.[ISI][Medline]
Yaka R, Yinon U, Wollberg Z (1999) Auditory activation of cortical visual areas in cats after early visual deprivation. Eur J Neurosci 11: 13011312.[ISI][Medline]
Zuo Z, De Vente J, Johns RA (1996) Halothane and isoflurane dose-dependent inhibit the cyclic GMP increase caused by N-methyl- D-aspartate in rat cerebellum: novel lacalization and quantitation by in vitro autoradiography. Neuroscience 74:10691075.[ISI][Medline]