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Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
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Department of Physiology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China
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Abstract |
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(Received 4 May 2004;
accepted after revision 21 July 2004;
first published online 22 July 2004)
Corresponding author J. He: Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China. Email: rsjufang{at}polyu.edu.hk
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Introduction |
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Various response patterns, including the phasic response, tonic response, and ‘off’ response have been reported in the MGB (Brugge et al. 1964; Suga, 1969; Aitkin & Webster, 1972; Brugge & Merzenich, 1973; He, 2002). The ventral division of the MGB shows more phasic responses with short latencies and the medial division shows tonic responses. Neurones showing ‘off’ or ‘on–off’ responses to acoustic stimuli are defined as ‘off’ or ‘on–off’ neurones and are often observed in the border region between the lemniscal and non-lemniscal MGB or in the non-lemniscal MGB (He, 2001, 2002).
Most of our understanding of the MGB has been obtained using extracellular electrophysiological recordings. Intracellular recordings have been carried out (1) on thalamic explants and slices, providing insights into the synaptic mechanisms of relay neurones in the MGB (Hu et al. 1994; Hu, 1995; Li et al. 1996; Tennigkeit et al. 1996, 1998; Bartlett & Smith, 2002; Mooney et al. 2004), (2) in the inferior colliculus with in vivo preparations, revealing that bats possess a putative inhibitory mechanism for duration tuning and that there are complex interactions between excitatory and inhibitory inputs for the processing of binaural signals (Casseday et al. 1994; Kuwada et al. 1997), and (3) in the auditory cortex with in vivo intracellular preparations, revealing layer-specific differences in the response characteristics of pyramidal neurones in the auditory cortex (Ojima & Murakami, 2002). However, experiments have never been carried out in the MGB with in vivo preparations. Suprathreshold neuronal firing detected with extracellular recording on the other hand cannot reveal the excitatory and inhibitory postsynaptic membrane responses. In order to understand the neuronal circuits that are related to the MGB, it is necessary to obtain subthreshold membrane responses to auditory stimuli with an in vivo preparation.
An in vivo intracellular experiment could allow us to correlate the response patterns, the membrane potentials, the subthreshold responses, and the anatomical locations of the MGB neurones. In the present in vivo intracellular study, we examined the auditory responses of the MGB neurones that were histologically identified by intracellular labelling with Neurobiotin. This is the first in vivo study to correlate the intracellular responses of auditory thalamic neurones with their locations in various subdivisions of the MGB.
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Methods |
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The experimental procedures were approved by the Animal Subjects Ethics Sub-Committee of The Hong Kong Polytechnic University.
Forty-eight guinea pigs were used for the intracellular recording experiments. Anaesthesia was initially induced with pentobarbital sodium (Nembutal, Abott, 35 mg kg–1, I.P.) and maintained by supplemental doses of the same anaesthetic (about 5–10 mg kg–1 h–1) during the surgical preparation and recording. Throughout the recording, the electrocorticograph was monitored to assess the level of anaesthesia. The animal was mounted in a stereotaxic device following the induction of anaesthesia. A midline incision was made in the scalp and a craniotomy was performed to enable vertical access to the MGB in the right hemisphere (He et al. 2002; Xiong et al. 2003). The head was fixed with two stainless steel bolts to an extended arm from the stereotaxic frame using acrylic resin. The left ear was then freed from the ear bar, so that the animal's head remained fixed to the stereotaxic device without movement.
Cerebrospinal fluid was released at the medulla level through an opening at the back of the neck. The animal was artificially ventilated. Both sides of the animal's chest were opened, and its body was suspended to reduce vibrations of the brain caused by intrathoracic pressure.
We used a glass pipette as the recording electrode, filling it with 0.5 M KCl (pH 7.6, 0.05 M Tris–HCl buffer). Using 3.0 M potassium acetate as the filling liquid in a pilot study, we also observed both excitatory postsynaptic potential (EPSP) and inhibitory postsynaptic potential (IPSP) responses to the auditory stimuli. The resistance of the electrode ranged between 40 and 90 M
. The electrode was advanced vertically from the top of the brain by a stepping motor (Narishige, Tokyo, Japan). After the electrode was lowered to a depth of 4–5 mm, the cortical exposure was sealed using low-melting-temperature paraffin. When the electrode was near or in the target area, it was slowly advanced at 1 or 2 µm per step.
Acoustic stimuli
Acoustic stimuli were generated digitally by a MALab system (Kaiser Instruments, Irvine, CA, USA), which was controlled by a Macintosh computer (Semple & Kitzes, 1993; He, 1997). Acoustic stimuli were delivered to the guinea pig via a dynamic earphone (Bayer DT-48). The sound pressure level (SPL) of the earphone was calibrated over a frequency range of 100 Hz to 35 kHz under the control of a computer using a condenser microphone (Brüel & Kjær, Nærum, Denmark; 1/4 inch). The calibration was saved in the computer and used to compensate for the output intensity of each frequency (Semple & Kitzes, 1993). The animal was placed in a double-walled soundproofed room (NAP, Clayton, Australia). Repeated noise bursts and pure tones with intervals of 400 ms or longer and a 5 ms rise/fall time were used to examine neuronal responses. Noise bursts were white noise with frequencies ranging from 100 Hz to 35 kHz. Pure tones were those with a single frequency of 100 Hz –35 kHz.
Anatomical confirmation
The recording pipette was filled with Neurobiotin (Vector; 1–2% in 1 M KCl) and the tracer was injected into 1–2 neurones of each animal after physiological recordings were taken of the 17 guinea pigs. Other animals were used for the physiological recordings only and were killed with an overdose of anaesthetic. Neurobiotin was delivered into the neurone by passing rectangular depolarizing current pulses (150 ms, 3.3 Hz, 2 nA) for 1–4 min. The animals were then deeply anaesthetized with sodium pentobarbital and perfused transcardially with 0.9% saline followed by a mixture of 4% paraformaldehyde in a 0.1 M phosphate buffer (pH 7.3). The brains were removed and postfixed in 4% paraformaldehyde overnight, then moved to a 0.1 M phosphate buffer containing 30% sucrose. The thalami were cut transversally using a freezing microtome at a thickness of 90 µm. Serial sections were collected in 0.01 M potassium phosphate-buffered saline (KPBS, pH 7.4) and then incubated in 0.1% peroxidase-conjugated avidin-D (Vector) in KPBS with 0.5% Triton X-100 for 4–6 h at room temperature. After the detection of peroxidase activity with 3',3'-diaminobenzidine (DAB), sections were examined under the microscope and photographed. Those sections containing labelled neurones were mounted on gelatin-coated slides and counterstained with neutral red (1%, Sigma).
Parcellation of the MGB was based on the neural architecture of the neutral red staining with reference to published literature (Redies et al. 1989; Redies & Brandner, 1991; He, 2001).
Data acquisition and analysis
Upon penetrating the membrane of a cell, the electrode detected the negative membrane potential. After amplification, the membrane potential as well as the auditory stimulus was stored in the computer with the aid of commercial software (AxoScope, Axon).
The direct current (DC) level of the recording electrode was frequently checked and set to zero during the experiments. The DC level after each recording was used to compensate for the membrane potential of some neurones, especially for those with a long recording time. Neurones showing a resting membrane potential of < –50 mV and spontaneous spikes (if any) of > 50 mV were included in the present study.
The amplitude and duration of the EPSP and IPSP were measured. The beginning and end of each EPSP and IPSP were defined at a threshold of 10% of their amplitude. The rise time was defined as the period between 10% and 90% of their amplitude, and the decay time was defined as the period between 90% and 10% of their amplitude. To standardize the EPSPs and IPSPs across the neurones, measurements of the neuronal responses were made when the membrane potential was close to –60 mV. A current was injected through the recording electrodes to manipulate the membrane potential of the recorded neurones when we examined the low-threshold calcium spikes and the membrane-potential dependence of the EPSP and IPSP.
Numerical results are expressed as mean ± standard deviation (S.D.). Student's t test was used to examine the differences in the shapes of EPSPs and IPSPs, using 95% as the confidence level (P < 0.05).
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Results |
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Excitatory auditory responses: EPSP responses
Forty-two neurones showed EPSP responses to acoustic stimuli, as depicted in the examples shown in Fig. 1. All neurones in Fig. 1 responded to an acoustic stimulus with an EPSP. The neurones in Fig. 1A and B responded with a train of action potentials to the noise-burst stimulus. The neurone in Fig. 1A showed a train of action potentials to acoustic stimuli and trains of spontaneous action potentials. The neurones in Fig. 1B and C showed auditory responses similar to those in Fig. 1A. They displayed a prolonged EPSP with spikes on it, but only a single spontaneous action potential was observed. Neurones in Fig. 1D and E showed a spike or a few spikes on the rising phase of the EPSP, while the neurone in Fig. 1F showed a delayed spike on the top of the EPSP and that in Fig. 1G showed only an EPSP without any spike.
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Inhibitory postsynaptic potential responses to acoustic stimuli
Acoustic stimuli evoked an IPSP in 25 neurones. The neurones in Fig. 2A and B showed an onset spike before the IPSP, while the neurones in Fig. 2C and D showed only an IPSP. Neurones showing onset spikes can be categorized as EPSP–IPSP neurones, as the onset spikes were mostly triggered by the onset EPSP that could be distinguished once the time axis was expanded. Although the IPSPs differed in shape, they normally lasted for a long period of time (all for over 100 ms).
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Seventeen neurones with either an EPSP or IPSP response pattern were successfully injected with Neurobiotin and counterstained with neutral red. Their anatomical locations were analysed together with their auditory response patterns. Of 11 neurones showing an EPSP response pattern, 7 were located in the MGv (lemniscal MGB) and 4 in the non-lemniscal MGB. Six neurones showed either an IPSP pattern or an EPSP–IPSP pattern. All of these neurones were located in the non-lemniscal MGB.
Figure 3 shows the physiology, morphology, and anatomical locations of six MGB neurones. Three of them showed an EPSP response pattern to acoustic stimuli (Fig. 3A–C) and two showed a spike/IPSP pattern (Fig. 3D and E). The neurones in Fig. 3A and C were all located in the MGv and those in Fig. 3D and E were located in the non-lemniscal MGB. Due to the small number of neurones sampled in the present study, we categorized the neurones based on their physiological properties.
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The resting membrane potential changes with time and state. Both auditory-evoked EPSPs and IPSPs were dependent on the resting membrane potential, as shown in the examples in Fig. 4A. The dependence of the amplitudes of EPSPs and IPSPs on a resting membrane potential of above –73 mV was examined using five neurones each (Fig. 4B). Both EPSPs and IPSPs showed a positive correlation with the resting membrane potential. This result indicated that with a resting membrane potential of above –73 mV, the neurones exhibited a stronger response to the same stimulus when their resting membrane potential was higher, and vice versa.
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Different from the after-hyperpolarization potential (AHP) which immediately follows a spike, the neurone in Fig. 5B showed an IPSP that occurred between 7.0 and 13.9 ms after a spontaneous spike or spikes (latency was measured from the first spontaneous spike in cases where there were two such spikes). This neurone also responded to a noise-burst stimulus with an IPSP (Fig. 5A). Although there were more zigzags in the acoustically evoked IPSPs than in the IPSPs after the spontaneous spike(s), the IPSPs had a similar shape and lasted for a similar length of time of about 100 ms.
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With a resting membrane potential of above –70 mV, the thalamic neurones showed normal spikes, similar to those shown in Figs 1–5. The neurone in Fig. 6A responded to a noise-burst stimulus with a normal spike when the membrane potential was –66 mV. It responded to the same stimulus with an EPSP or a spike when the membrane potential was hyperpolarized to –74 mV. However, the neurones changed their response pattern to a low-threshold calcium spike (LTS) when the membrane potential was further hyperpolarized to –77 mV. With an even lower membrane potential of –85 or –90 mV, the neurone responded to the same noise-burst stimulus with a spike burst. The lower the membrane potential, the more spikes were evoked in each burst.
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It was also interesting to note that the depolarization before the LTS spikes or LTS spike burst, which was evoked by the acoustic stimulus, was larger when the steady-state membrane potential was more hyperpolarized.
Three examples of auditory IPSP neurones are shown in Fig. 7. The neurone in Fig. 7A showed an EPSP, followed by an IPSP when the membrane potential was higher than –72 mV. The IPSP disappeared and changed to an EPSP with a spike/spike burst when the membrane potential was hyperpolarized to below –78 mV. The neurone responded to the same stimulus with a slow EPSP and a spike/spike burst after a build-up, which was likely to be an LTS spike/spike burst. Both neurones in Fig. 7B and C responded to a noise-burst stimulus with an IPSP when their membrane potential was above –60 mV, but changed to an LTS spike/spike burst when their steady-state membrane potential was hyperpolarized to –85 mV. It was interesting to note that the neurone did not seem to be responsive to acoustic stimuli when the membrane potential was about –65 mV, while it responded to the same stimulus at other membrane potentials (Fig. 7B).
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Nine ‘off’ and two ‘on–off’ neurones were recorded in the present study. The neurones in Fig. 8A and B are ‘off’ neurones and that in Fig. 8C is an ‘on–off’ neurone. The neurone in Fig. 8A responded to noise-burst stimuli of 100, 200 and 400 ms in duration. It showed better responses to stimuli with longer durations than to those with 100 ms in duration. The neurone also showed a shorter latency of 50 ms to the offset of a 400 ms stimulus, as compared with a latency of 125 ms to a 200 ms stimulus. In response to noise-burst stimuli with a duration of 200 ms, the neurone in Fig. 8B showed an ‘off’ response with either an EPSP or an EPSP and a spike. The resting membrane potential of the neurone was –63 mV. When the duration of the stimulus was 100 ms, this neurone responded with a varying latency of between 48 ms and 235 ms after the offset of the stimulus. This neurone responded to a noise-burst stimulus of 200 ms in duration with an EPSP of a similar size, a similar probability of firing, and a similar mean latency. The latency of the responses to different trials of a 200 ms stimulus was, however, more consistent (about 125 ms; range: 103–142 ms) than to those of a 100 ms stimulus (range: 48–235 ms).
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Localization of an ‘off’ neurone
Only one ‘off’ neurone was successfully injected with Neurobiotin, as shown in Fig. 9. The neurone was located in the caudomedial nucleus of the MGB (MGcm), clearly outside the MGv, as revealed with neutral red counterstaining.
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Discussion |
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With extracellular recordings, previous investigators have categorized auditory response patterns in the cortex, the MGB, and the inferior colliculus (IC) into the following categories: (1) sustained, (2) inhibitory, (3) phasic ‘on’ firing, and (4) phasic ‘off’ firing (Suga, 1969; Aitkin & Webster, 1972; Brugge & Merzenich, 1973; Aitkin & Prain, 1974; He, 2002). It is also known that the response patterns change when the stimulus changes (Brugge et al. 1970; Aitkin & Webster, 1972; Aitkin & Prain, 1974).
The sustained response pattern could be caused by either a long-lasting EPSP or an EPSP followed by a fast rebounded response that was sustained while the stimulus was on. The latter was classified as tonic response in the present study. This is the first study to report quantitatively on the amplitude and duration of the EPSPs evoked by auditory stimuli in the MGB. The mean amplitude of the EPSPs in the MGB is comparable to those of EPSPs in the auditory cortex, where amplitudes of several millivolts to about 20 mV were observed (Ojima & Murakami, 2002). The amplitudes of the EPSPs in the IC showed a relatively small value of below 10 mV for most neurones (Kuwada et al. 1997). It is surprising to note that the maximal amplitude of the EPSPs in MGB neurones reached 40 mV in the present study.
In a recent intracellular study on thalamic slices no difference in intrinsic membrane features and synaptic responses was observed between neurones in the lemniscal and non-lemniscal MGB (Bartlett & Smith, 1999). However, in a thalamic explant preparation, where the neurones in the caudal MGB can be unambiguously identified, the synaptic response pattern and membrane potential differ significantly between MGv and the dorsal division of the MGB (MGd) (Hu, 1995, 2003; Mooney et al. 2004). In the accompanying paper (Xiong et al. 2004), we will examine the potential relationship between corticofugal modulation and auditory response patterns of MGB neurones.
One-quarter of the neurones reported in the present study responded to an acoustic stimulus with either an IPSP or an EPSP followed by an IPSP. As the size of the sample in the present study was small, we did not further categorize these neurones. The IPSP pattern has also been observed in the IC (Kuwada et al. 1997) but not in the auditory cortex (Ojima & Murakami, 2002). The acoustically evoked IPSPs in the IC could result from inhibitory ascending terminals from the brainstem or terminals of inhibitory IC neurones (Kuwada et al. 1997).
Locations of EPSP and IPSP neurones
Of the 11 EPSP neurones localized in the MGB, 7 were located in the lemniscal MGB and 4 were located in the non-lemniscal MGB. Judging from the fact that the mean response latency of the EPSP neurones was 15.7 ms, it is also reasonable to assume that the EPSP neurones were not all from the lemniscal MGB, where the mean latency has been reported to be 9.0 ms (He, 2002). A further analysis of the correlation between the response patterns of the EPSP neurones and their locations is to be conducted after we have collected a significant number of labelled neurones with characterized auditory properties. It is worth noting that neurones showing either a pure IPSP response or an IPSP preceded by an EPSP or spike(s) were located in the non-lemniscal MGB.
Potential neural circuitries
It is speculated that the EPSP responses were caused by excitatory input to the thalamic relay neurones. Since EPSP neurones may occur in both the lemniscal and non-lemniscal MGB, they showed a wider variation in latency of response. The neurones located in the lemniscal MGB mainly receive input from the central nucleus of the IC and those located in the non-lemniscal MGB receive input from the external nuclei of the IC (Calford & Aitkin, 1983; Rouiller & de Ribaupierre, 1985; Winer, 1992). Thalamic relay neurones receive excitatory inputs both ascending from the midbrain and brainstem and descending from the cortex. Some long-latency EPSPs observed in the present study might be caused by the descending input from the cortex after the latter was activated by the acoustic stimuli. However, the issue needs to be addressed in a further study.
There are three potential inputs that cause inhibitory potentials on thalamic relay neurones: (1) thalamic interneurones, (2) GABAergic IC neurones, and (3) thalamic reticular nucleus (TRN) neurones (Winer et al. 1996; Peruzzi et al. 1997). Since there are very few interneurones in the thalamus of a guinea pig (< 1%, Spreafico et al. 1983, 1994; Winer & Larue, 1996; Arcelli et al. 1997), it is unlikely that the IPSPs with a mean amplitude of 8.3 mV and a mean duration of 208.5 ms were caused by thalamic interneurones.
All of the acoustically evoked IPSP neurones were located in the non-lemniscal MGB. This is in contrast to that found in the slices (Peruzzi et al. 1997), suggesting that auditory stimulation delivered to the in vivo animals and artificial electrical shocks to the slice will not always give rise to similar synaptic responses. Our previous extracellular study suggests that the TRN feedback is to the non-lemniscal MGB rather than to the lemniscal MGB (He, 2003a). Neurones in the TRN receive wide input from the MGB, including the MGv, with a short latency and project widely back to the MGB (Ohara et al. 1980; Bourassa & Deschênes, 1995; Liu et al. 1995a; Cox et al. 1997; Pinault et al. 1997). Recent studies indicate that the TRN terminals exert a very strong inhibitory effect on thalamic relay neurones (Bartlett et al. 2000; Golshani et al. 2001), possibly through giant GABAergic terminals that have been found only in the non-lemniscal MGB (Winer et al. 1999). This provides an explanation for the present result, in which acoustically evoked IPSP neurones were only found in the non-lemniscal MGB. Some non-lemniscal MGB neurones that showed a pure IPSP pattern in response to the auditory stimulus might receive the TRN inhibitory input before the arrival of the relatively long latency ascending excitatory input from the external nuclei of the IC. The TRN neurones may, on the one hand, be activated by input from the lemniscal MGB; on the other hand, they inhibit the non-lemniscal MGB since they receive wide projections from the MGB and send wider projections, possibly mainly to the non-lemniscal MGB (Shosaku & Sumitomo, 1983; Pinault et al. 1997; Crabtree, 1998).
Although we do not have enough evidence to reject the second potential source of inhibitory input evoking the IPSPs observed in the present report, the result in Fig. 5 favours the third source, i.e. TRN. The neurone in Fig. 5 responded to an acoustic stimulus with an IPSP at a latency of 21 ms. This neurone also showed an IPSP after each spontaneous spike or spike burst. As there was a time lag of 7.0–13.9 ms between the spontaneous spike (the first spontaneous spike in cases where there were two such spikes) and the IPSP (Fig. 5B), the IPSP should not be taken as an AHP. A time lag of 7.0–13.9 ms is in fact long enough for the neural signal to traverse two synapses, i.e. from the MGB neurone to the TRN neurone, and then back to the MGB neurone. It is unlikely that the spontaneous spikes and the IPSPs were triggered by two synchronized sources in the IC, although this possibility cannot be excluded. Given that TRN neurones are known to mediate a diverse inhibitory effect in the thalamus (Cox et al. 1997; Crabtree, 1998, 1999), the most logical explanation is that the spontaneous spikes of the MGB neurone activated a TRN GABAergic neurone(s), which in return inhibited the MGB neurone, resulting in a strong IPSP.
Another possible inhibition on thalamic relay neurones is from the presynaptic dendrites of the interneurones (Ralston et al. 1988; Liu et al. 1995b). Presynaptic dendrites account for only < 6% of the total number of terminals in a guinea pig's thalamus (Rinvik et al. 1987). With such a small population of interneurones, the presynaptic dendrites are unlikely to cause such a strong inhibition on their own.
Dependence of the postsynaptic potential on the resting membrane potential
Both the acoustically evoked EPSP and IPSP depended on the resting membrane potential. The higher the resting membrane potential the larger was the EPSP and IPSP when the resting membrane potential was above –73 mV. The implication of this result needs to be further investigated. The larger EPSPs that occurred upon depolarization of the membrane may result from a voltage-dependent activation of NMDA receptors as they were released from Mg2+ blockade (Hu, 1995), whereas enhanced IPSPs reflect an increased driving force as the membrane potential shifts away from that for Cl– or K+ reversal potentials.
However, the situation changed when the resting membrane potential was hyperpolarized to a level below –73 mV. The IPSP responses to the acoustic stimuli changed to EPSP responses, and the EPSP responses showed bigger amplitudes than those at –70 mV. When the membrane potential was further hyperpolarized to –80 and –90 mV, the response changed from single spikes to spike bursts with a much greater EPSP. This subthreshold electrical activity has been considered to be low-threshold calcium spike(s) (LTS) (Llinás & Yarom, 1981; Jahnsen & Llinás, 1984a; Deschênes et al. 1984). Thalamic relay neurones have a high level of a1G calcium channel gene expression, which leads to LTS spikes or LTS bursts generated with a T-type Ca2+ current (Jahnsen & Llinás, 1984a,b; Coulter et al. 1989; McCormick & Feeser, 1990; McCormick & Bal, 1994; Bal et al. 1995; Huguenard, 1996; Sherman & Guillery, 1996; Pape, 1996; Talley et al. 1999). We also observed that, in most neurones, a single LTS could change to an LTS burst when the membrane potential was further hyperpolarized to below –80 mV (Figs 6 and 7). The LTS-evoked high-frequency burst following an auditory stimulation may underlie some of the bursting auditory response recently described in the MGB (He & Hu, 2002).
The result of the present study, in which LTS spikes appeared when the steady-state membrane potential was below –70 mV, agrees with that of a previous report (Steriade, 2001b). In other thalamic regions of in vivo animals, tonic firing was observed at depolarized levels, which inactivated the calcium current, and burst firing was found at hyperpolarized levels, which activated the calcium current (Deschênes et al. 1984; Steriade & Deschênes, 1984; Mulle et al. 1986; Paré et al. 1987). With an in vivo preparation, Timofeev et al. (2001) found that the amplitude of depolarization before the calcium spikes had a negative correlation with the conditioning membrane potential.
With the use of natural stimuli, we could successfully trigger the LTS spikes/bursts from in vivo animals. The functional implications of the LTS bursts have been debated in the past few years (Swadlow & Gusev, 2001; Sherman, 2001b; Steriade, 2001a). We found that neurones showed burst responses to acoustic stimuli under two very different states: (1) with a normal membrane potential (Fig. 1A–C), and (2) with a highly hyperpolarized membrane potential (Fig. 6). The bursts discussed in the previous debate were clearly of the latter kind (Swadlow & Gusev, 2001; Sherman, 2001a,b; Steriade, 2001a). Although we are uncertain about the physiological implications of the bursts elicited by the two states, these bursts have a stronger impact than a single spike (Cash & Yuste, 1998).
‘Off’ and ‘on–off’ neurones
‘off’ neurones have been reported in the cochlear nucleus, the superior olivary complex, the IC, the MGB, and the auditory cortex (Suga, 1964; Neuweiler et al. 1971; Grinnell, 1973; Aitkin & Prain, 1974; Lesser et al. 1990; Grothe et al. 1992; He et al. 1997; He, 2001, 2002). Many ‘off’ neurones are duration selective and most duration-selective neurones in the IC are ‘off’ neurones (He et al. 1997; Casseday et al. 1994, 2000; Ehrlich et al. 1997; Brand et al. 2000; He, 2002). The ‘off’ neurone in Fig. 8A was a long-duration selective neurone. Consistent with a previous finding (He, 2002), no short-duration-selective ‘off’ neurones were found in the MGB in the present study. The present result in which the ‘off’ neurone was located in the non-lemniscal MGB agreed with that of a previous extracellular recording study (He, 2001).
The neurone in Fig. 8B responded to a 200 ms stimulus with a more precise latency than to a 100 ms stimulus, suggesting that the response latency or the deviation of the latency could be another component encoding the information on the stimulus. This result, which is consistent with that from a previous in vitro study (Hu, 1995), provides evidence to support the notion that neurones encode auditory information not only with a spike number, but also with the temporal feature of the neuronal response (Middlebrooks et al. 1994; He et al. 1997; He, 1998).
Functional implications
Neurones in the lemniscal MGB showed mostly EPSP responses to acoustic stimuli, while those in the non-lemniscal MGB showed both EPSPs and IPSPs to acoustic stimuli. The selective inhibition in the non-lemniscal MGB might be related to the giant GABAergic terminals that were found only in the non-lemniscal MGB (Winer et al. 1999). By selectively switching off some of the non-lemniscal MGB neurones that are multisensory or involved in adjusting the global activity of the auditory cortex (LeDoux et al. 1990; He, 2003b), the ascending pathway is able to prepare the auditory cortex to receive subsequent auditory information to avoid the influence of other sensory inputs. This function might be particularly important while an animal is sleeping. Since the non-lemniscal MGB during sleep is more likely to be in a state of oscillation, which involves the auditory cortex (Steriade, 2000, 2001b; He, 2003b), the selective inhibition of the non-lemniscal MGB may suppress the oscillation, and hence release the cortex from oscillation to receive the auditory information, which is forwarded via the lemniscal MGB.
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Footnotes |
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References |
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