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The Journal of Neuroscience, February 1, 1998, 18(3):895-904
Slow Synaptic Inhibition in Nucleus HVc of the Adult Zebra
Finch
Marc F.
Schmidt1 and
David J.
Perkel2
1 Division of Biology, California Institute of
Technology, Pasadena, California 91125, and 2 Department of
Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania
19104-6074
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ABSTRACT |
Nervous systems process information over a broad range of time
scales and thus need corresponding cellular mechanisms spanning that
range. In the avian song system, long integration times are likely
necessary to process auditory feedback of the bird's own vocalizations. For example, in nucleus HVc, a center that contains both
auditory and premotor neurons and that is thought to act as a gateway
for auditory information into the song system, slow inhibitory
mechanisms appear to play an important role in the processing of
auditory information. These long-lasting processes include inhibitory
potentials thought to shape auditory selectivity and a
vocalization-induced inhibition of auditory responses lasting several
seconds. To investigate the possible cellular mechanisms of these
long-lasting inhibitory processes, we have made intracellular recordings from HVc neurons in slices of adult zebra finch brains and
have stimulated extracellularly within HVc. A brief, high-frequency train of stimuli (50 pulses at 100 Hz) could elicit a hyperpolarizing response that lasted 2-20 sec. The slow hyperpolarization (SH) could
still be elicited in the presence of glutamate receptor blockers,
suggesting that it does not require polysynaptic excitation. Three
major components contribute to this activity-induced SH: a long-lasting
GABAB receptor-mediated IPSP, a slow afterhyperpolarization requiring action potentials but not Ca2+ influx, and
a long-lasting IPSP, the neurotransmitter and receptor of which remain
unidentified. These three slow hyperpolarizing events are well placed
to contribute to the observed inhibition of HVc neurons after singing
and could shape auditory feedback during song learning.
Key words:
birdsong; avian; IPSP; GABAB; auditory; motor
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INTRODUCTION |
In oscine songbirds, nucleus HVc
(see Fig. 1) is a crucial forebrain center for organizing singing
behavior (Nottebohm et al., 1976 ; McCasland, 1987; Yu and Margoliash,
1996), and it contributes to generating the motor patterns for song (Vu
et al., 1994). HVc also receives auditory input (Fortune and
Margoliash, 1995; Vates et al., 1996) and responds to playback of
complex auditory stimuli (Katz and Gurney, 1981; Margoliash, 1983;
Margoliash and Konishi, 1985; Lewicki, 1996). In many cases, these
highly selective auditory responses are thought to occur as a
consequence of complex interactions between long-lasting IPSPs and
intrinsic bursting properties (Lewicki and Konishi, 1995; Lewicki,
1996). An intriguing link between auditory and motor functions within
HVc of adult zebra finches is the observation that auditory responses
become inhibited during and after singing (McCasland and Konishi,
1981). Because auditory inputs into other areas of the song system
originate from HVc (Williams, 1989; Doupe and Konishi, 1991; Doupe,
1993; Vicario and Yohay, 1993), inhibition of auditory inputs in this
nucleus during singing may serve an important role in the temporal
gating of auditory feedback into the song system. The slow IPSPs
observed during auditory responses as well as the inhibition of
auditory responses after singing could have profound effects on the
processing of auditory information in the adult as well as during song
learning.
Long-lasting inhibition could be caused by the maintained release
of a short-lasting inhibitory neurotransmitter (e.g., GABA) under the
control of a long-lasting network response involving prolonged firing
of action potentials (Wagner et al., 1994), or alternatively by a
single long-lasting inhibitory synaptic event. Slow hyperpolarization
mediated by GABAB receptor activation has been observed in
many different areas of the mammalian CNS (Newberry and Nicoll, 1984;
Connors et al., 1988; Dutar and Nicoll, 1988; Allerton et al., 1989).
These IPSPs, however, generally last <1 sec (Alger, 1984; Newberry and
Nicoll, 1984). Longer-lasting IPSPs that continue for many seconds have
been described in only a few cases and may be mediated by 5-HT,
norepinephrine, or acetylcholine (Dodd and Horn, 1983; Egan et al.,
1983; Pan et al., 1989). Neuropeptides, which also can cause
hyperpolarization (Pepper and Henderson, 1980; Pittman and Siggins,
1981; Williams et al., 1982), have been suggested as potential
candidate neurotransmitters for IPSPs that last many seconds; a
striking example of a slow peptide-mediated synaptic event has been
described by Jan and Jan (1982).
We have recorded intracellularly from adult male zebra finch HVc
neurons in brain slices to investigate whether the physiological properties within HVc could account for the long-lasting inhibition observed in HVc in vivo (McCasland and Konishi, 1981).
High-frequency stimulation, approximating levels of activity observed
during singing (McCasland, 1987; Yu and Margoliash, 1996), caused a
slow IPSP lasting 2-20 sec. Blockade of glutamatergic excitatory
transmission reduced the amplitude of the hyperpolarization but did not
alter its slow time course, suggesting an intrinsically slow mechanism that did not require a polysynaptic network. Pharmacological dissection of this hyperpolarization revealed at least three components of the
inhibition.
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MATERIALS AND METHODS |
Preparation of slices and electrophysiological
recording. Adult zebra finches (Taeniopygia guttata)
were obtained from a breeding colony at Caltech as well as from local
suppliers near Los Angeles and Philadelphia. Slices were prepared as
described previously (Mooney, 1992; Perkel and Nicoll, 1993). Briefly,
birds were anesthetized with halothane or isoflurane and decapitated.
The brain was removed rapidly and placed in ice-cold artificial
cerebrospinal fluid (ACSF) that had been bubbled with 95%
O2/5% CO2. Composition of the ACSF was
(in mM): NaCl 134, KCl 2.5, NaH2PO4 1, NaHCO3 26, D-glucose 12, CaCl2 2.5, MgSO4 1.5. The brain was cut midsagittally with a razor
blade and parasagittal slices (400 µm thick) were prepared using a
vibrating microtome. Slices were stored at room temperature on porous
membrane (Nucleopore, Cambridge, MA) at the interface of ACSF and
humidified 95% O2/5% CO2 or submerged in bubbled ACSF. For recording, a slice was transferred to a submersion chamber where it was superfused with pregassed ACSF.
Intracellular electrodes were filled with 4 M potassium
acetate and had DC resistances of 70-140 M . Stable intracellular recordings were routinely obtained from neurons in nucleus HVc, the
borders of which were clearly defined even in the unstained tissue.
Resting potential and input resistance were closely monitored and
remained stable for the duration of the recording, commonly 2-5 hr.
One or more stainless steel bipolar stimulating electrodes (impedance
2-5 M) were placed within HVc, usually near the posterior or
anterior pole (Fig. 1B). We stimulated somata and
fibers within HVc (100 µsec duration; constant voltage, 5-60 V)
because input pathways to HVc are not segregated well enough to
stimulate one specifically. Moreover, stimulation outside of HVc would
likely cause antidromic activation of HVc outputs, which exit across a
broad region (Nottebohm et al., 1982).
Signals were amplified using an Axoclamp 2A (Axon Instruments, Foster
City, CA), low-pass filtered, and digitized at twice the filter cut-off
frequency. Intracellular records are presented here as the average of
two to three consecutive traces. Analysis included fitting a single
exponential function to the decay phase of a synaptic potential using a
least-squares algorithm. Average values of response amplitudes or
best-fit time constants are presented as the mean ± SD. The
Student's t test, paired or unpaired, was used as
indicated.
Materials. Chemicals were obtained from Sigma (St. Louis,
MO), except as noted. DMSO was purchased from Fisher Scientific (Pittsburgh, PA). The AMPA glutamate receptor antagonist
6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the NMDA glutamate
receptor antagonist DL-2-amino-5-phosphonovaleric acid
(APV), and the opiate antagonist naloxone were obtained from Research
Biochemicals (Natick, MA). The GABAB receptor antagonist CGP 35348 was a gift from CIBA-Geigy (Basel, Switzerland). Except as
noted, all drugs were added to the superfusion medium by dilution of a
stock solution made in water. Stock solutions of CNQX were made in
DMSO, resulting in a final concentration of DMSO of 0.1-0.2%, which
when added alone did not affect any of the responses observed. Bicuculline methiodide (BMI) was dissolved directly into the ACSF.
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RESULTS |
High-frequency stimuli in HVc elicit a slow
depolarization/hyperpolarization sequence lasting many seconds
We recorded intracellularly from HVc neurons and activated
synaptic inputs via a stimulating electrode placed within nucleus HVc
(Fig. 1B). In selecting
a stimulation pattern, we were guided by reported high firing rates
observed during singing (McCasland, 1987; Yu and Margoliash, 1996).
Single high-frequency trains of synaptic stimuli (50 pulses; 100 Hz)
caused a slow depolarization followed by an unusually slow
hyperpolarization (SH) lasting up to 20 sec (Figs.
2A,
3C). The hyperpolarization was often punctuated by
small depolarizing deflections (Fig. 2A). The overall
amplitude of the slow depolarization/hyperpolarization (SDH) appeared
to depend on the number of pulses in the stimulus train (Fig.
3A). Although we have not
performed a systematic analysis of the stimulus parameters, in four of
four neurons, the SH amplitude was near maximal with a stimulus train
of 20-50 pulses (Fig. 3B). Its slow time course was
apparent after only five stimuli (Fig. 3B). We were able to
elicit an SDH in 66% of the cells tested (57/86 neurons). This
percentage should be viewed as a rough approximation because it is
subject to positioning of the stimulating electrode as well as sampling
bias. In cells in which a single train gave rise to an SDH, a similar
SDH was also elicited by a more complex stimulus consisting of five
pulses at 100 Hz repeated five times at 5 Hz.
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Figure 1.
A, Schematic diagram of the song
system showing the various connections of nucleus HVc. Nucleus
HVc is part of the motor pathway for song production
(thick outline), sending a projection to nucleus RA. RA projects to brainstem motor and premotor neurons
that control the Syrinx and muscles of
Respiration. HVc also projects to Area X,
which forms part of the anterior forebrain loop, a circuit essential
for song learning. Auditory inputs to HVc originate from
NIf as well as from field L, although
field L inputs may reach HVc indirectly via the shelf surrounding the
nucleus. The broken line between field L and NIf
indicates that this connection involves several synapses within the
auditory forebrain. HVc also receives major inputs from the forebrain
nucleus m-MAN and the thalamic nucleus
UVa. HVc, used here as the proper name of
the nucleus (Brenowitz et al., 1997), also referred to as the high vocal center (HVC); RA, nucleus robustus
archistriatalis; UVa, nucleus uvaeformis;
L, field L; NIf, nucleus interfacialis;
m-MAN, medial portion of the magnocellular nucleus of
the anterior neostriatum; L-MAN, lateral portion of the
magnocellular nucleus of the anterior neostriatum; DLM,
medial nucleus of the dorsolateral thalamus. B,
Photomicrograph of the experimental preparation used in this study.
Parasagittal brain slices were cut through the zebra finch brain.
Stimulating electrodes were placed near the posterior or anterior pole
of the nucleus. Intracellular recordings were obtained from neurons in
nucleus HVc, the borders of which were clearly defined even in the
unstained tissue. Dorsal is up; anterior is to the right. Scale bar,
500 µm.
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Figure 2.
Slow depolarizing/hyperpolarizing sequence after
repetitive synaptic stimulation of an HVc neuron. A,
This sample trace illustrates the potential change
caused by stimulating within nucleus HVc at 100 Hz for 0.5 sec. Such
stimulation caused this HVc neuron to exhibit a slow depolarization
followed by a long-lasting hyperpolarization. In this case the decay
time constant of the hyperpolarization was 2.6 sec, and the resting
membrane potential was  65 mV. Arrow indicates onset of
stimulation. B, This schematic representation of the
slow depolarizing/hyperpolarizing sequence illustrates how waveform
parameters were measured. A, Time-to-peak for
the depolarization B. Amplitude of peak
depolarization. C, Time-to-peak hyperpolarization. D, Amplitude of peak
hyperpolarization. E, Decay time constant of the
hyperpolarization. See Table 1 for recorded values.
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Figure 3.
Effect of stimulation pattern on amplitude and
time course of the SH. A, HVc neurons were subjected to
different numbers of stimuli (A1, 5 pulses; A2,
20 pulses; A3, 50 pulses) delivered at 100 Hz. The amplitude
and the time course of both the slow depolarization and the
hyperpolarization were directly dependent on the number of pulses used
in the stimulus. Dotted line indicates the resting
potential for the cell illustrated (58 mV). B, Peak amplitude and decay time constant of the SH component varied with the
number of stimuli. Peak amplitude (filled
circles) of the SH increased rapidly with the number of stimuli
reaching 80% of maximum with a 20-pulse stimulus. Decay time constant
(open circles) increased from 5 to 10 pulses and then
leveled out around 4 sec. C, Histogram for all cells
recorded showing the range of decay time constants ( ) for the SH
obtained using the standard 50-pulse stimulation. Time constants tended
to cluster around 5 sec.
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We measured the components of the SDH illustrated in Figure
2B, and the values are summarized in Table
1. In most of the cells recorded (26/31)
(Fig. 3C), the decay time constant fell within the range of
2.6-6.9 sec, with a mean of 4.8 ± 1.3 sec for those 26 neurons.
One outlier had a decay time constant of 639 msec, whereas four others
fell in the range of 13-21 sec.
The slow depolarization/hyperpolarization can occur with blocked
network excitation
To test whether the SDH response resulted from persistent
polysynaptic network activity, we blocked excitatory neurotransmission pharmacologically. Vu and Lewicki (1994) have reported blockade of
EPSCs in HVc by ionotropic glutamate receptor antagonists. We used 20 µM CNQX to block AMPA receptors (Honoré et al.,
1988) and 100 µM APV to block NMDA receptors (Davies et
al., 1981). This combination of antagonists blocked monosynaptic EPSPs
evoked by single-shock stimulation (Fig.
4A) and almost always
(19/20) reduced the amplitude of the SDH response (Fig.
4B). The overall effect of blocking glutamatergic
transmission on the SDH response was quite variable. The depolarization
was often eliminated (9/14), whereas in the remaining five cells it was
reduced to 43 ± 13% of its control value (Table 1). The
time-to-peak depolarization was unchanged with ionotropic glutamatergic
transmission blocked (p > 0.89). The effect of
CNQX and APV on the hyperpolarization amplitude was particularly
variable. The peak amplitude in the presence of the blockers averaged
60 ± 53% of control (n = 20; range, 2-140%)
(Fig. 4C). The time-to-peak hyperpolarization was shortened.
Despite the changes in the amplitude values, the addition of CNQX and
APV did not significantly change the decay time constant of the SH
(p > 0.45; paired t test). Because
blockade of excitatory amino acid receptors should eliminate
polysynaptic responses, these results suggest that glutamatergic
excitatory connections remaining within the slice contribute
significantly to both the slow depolarization and hyperpolarization
responses. However, because a substantial portion of the SH remained
after blockade of ionotropic glutamate receptors, these data also
suggest that the hyperpolarizing component of the SDH may result from
direct activation of inhibitory neurons. Moreover, the time course of the SH appears not to depend on the activation of an extensive network
of excitatory glutamatergic connections.
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Figure 4.
Effect of ionotropic glutamate receptor
antagonists on synaptically evoked potentials in nucleus HVc.
A, A single-shock stimulus typically elicited a rapid
onset EPSP followed by an IPSP lasting several hundred milliseconds.
Stronger stimulation could elicit an action potential. Bath application
of the glutamate antagonists CNQX (20 µM) and APV (100 µM) blocked the EPSP and preserved the slow IPSP.
B, Bath application of CNQX/APV generally had a wide range of effects on the time course and amplitude of the SH elicited by
a fast train of stimuli (50 pulses at 100 Hz). These effects ranged
from partial decrease in amplitude of the hyperpolarization to nearly
complete blockade. This sample trace illustrates a typical example
(different cell from A), in which the amplitude of the SH is decreased by ~40% after blockade of excitatory transmission. C, This histogram illustrates the range of effects
observed after the addition of CNQX/APV. Although addition of glutamate
receptor antagonists always reduced the amplitude of the SH, the
overall level of reduction was quite variable. Percent reduction of the SH (measured at peak amplitude) ranged from 0 to 98%, with a median reduction near 50%. Two cells in which the SH grew after application of CNQX and APV are represented as 0% blockade here.
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The slow depolarizing response is mediated by activation of
GABAA receptors
To characterize the slow hyperpolarizing portion of the SDH, we
attempted to block the initial slow depolarizing phase of the response.
Previous studies have shown that GABAA receptor activation,
which is normally hyperpolarizing, can become depolarizing when neurons
are stimulated at high frequency (Andersen et al., 1980; Alger and
Nicoll, 1982; Staley et al., 1995). The addition of the
GABAA receptor antagonist BMI (40 µM) (Curtis
et al., 1970; Newberry and Nicoll, 1984) to neurons exhibiting a
substantial SDH in the presence of CNQX and APV completely blocked the
slow depolarizing response in all cases tested (Fig.
5) (n = 8). Blockade by
BMI left a hyperpolarization that sometimes, but not always, appeared
to have two decay phases. The slow phase measured in the presence of
CNQX, APV, and BMI had a decay time constant unchanged from that
measured before the addition of BMI (n = 8;
p > 0.3; paired t test). Although the decay
time course of the SH remained unchanged, the peak amplitude during
GABAA receptor blockade was larger (n = 8;
p < 0.05; paired t test) and occurred
sooner after stimulation (n = 8; p < 0.05; paired t test) than in the presence of just CNQX and
APV (see Table 1).
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Figure 5.
Effect of the GABAA receptor
antagonist bicuculline methiodide (BMI) on the
depolarizing phase of the synaptically evoked slow
depolarization/hyperpolarization sequence. High-frequency stimulation
(50 pulses at 100 Hz) was used to obtain an SDH sequence (Control) in the presence of CNQX (20 µM) and APV (100 µM). Addition of BMI (40 µM) in the continued presence of CNQX and APV completely blocked the depolarizing phase of the synaptic response. This blockade
of a depolarizing response by BMI was not unexpected, given previous
reports showing that stimulation at high frequency can cause
GABAA receptor-mediated events to become depolarizing (see
Results). The peak amplitude of the hyperpolarization significantly increased after addition of BMI, suggesting that the reversed GABAA depolarizing phase was masking part of the SH. On
average, the slow decay time constant remained unchanged in the
presence of BMI. In this case the decay time constants were 1.8 sec
(Control) and 2.2 sec
(BMI). The rise to peak hyperpolarization in the
presence of BMI often had a characteristic linear shape.
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When the membrane potential was shifted by injecting DC current, the
extrapolated reversal potential was approximately 95 mV (data not
shown), suggesting the SH is mediated by an increase in potassium
conductance. In two cases, the apparent reversal potential was shifted
to a depolarized level when the external potassium concentration was
raised (data not shown). A more detailed biophysical analysis of the SH
will require voltage-clamp techniques with better control of the
postsynaptic membrane potential.
Contribution of a long-lasting AHP to the
slow hyperpolarization
The SH was in some cases likely to be purely synaptic in nature
because it could be elicited in the absence of stimulus-induced antidromic action potentials (n = 6) (Fig.
2A). In many cases, however, despite the presence of
glutamate receptor blockade, stimulation within HVc produced action
potentials and created the possibility that a portion of the
hyperpolarization was caused by an action potential-induced slow
afterhyperpolarization (sAHP). These action potentials were not
unexpected, given the high degree of axonal arborization within HVc
(Katz and Gurney, 1981; Nottebohm et al., 1982; Nixdorf et al., 1989)
and were likely antidromic in nature because they (1) had rapid onset
times, (2) persisted in the presence of glutamatergic receptor
antagonists, (3) persisted in the presence of hyperpolarizing current,
and (4) were not blocked by the calcium channel blocker
CdCl2 (100 µM), which eliminated all synaptic
transmission.
Slow AHPs in nucleus HVc could be elicited by direct current
injection (Kubota and Saito, 1991) (Fig.
6) and were characterized by an initial,
rapidly decaying phase followed by a very slow component, the time
course of which resembled the decay time constant of the SH observed
after extracellular stimulation within HVc (compare Fig. 5 and Fig. 6).
The decay time constant of the two hyperpolarizations was directly
compared in 15 cells. The value was 5.4 ± 3.9 sec for the SH and
4.3 ± 2.4 sec (n = 15; p > 0.07; t test) for the sAHP. Thus, on the basis of the time course,
in cases in which extracellular stimulation caused antidromic action potentials the sAHP could have contributed to the SH.
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Figure 6.
Depolarizing current pulses cause a slow
afterhyperpolarization (sAHP). A, An example of rapid
action potentials elicited by direct current injection into an HVc
neuron (0.8 nA, 1 sec). B, Such current injection caused
an afterhyperpolarization with a relatively short time to peak but slow
decay time constant (4.1 sec). Resting membrane potential = 63
mV.
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In an attempt to discriminate between the synaptic component of the SH
and the sAHP, we sought a pharmacological means of selectively blocking
the sAHP. In agreement with Kubota and Saito (1991), we found that in
nucleus HVc, the slow phase of the sAHP is insensitive to the
broad-spectrum calcium channel blocker cadmium (Fig.
7A), suggesting that the
conductance is different from that of calcium-dependent sAHPs observed
in other systems (for review, see Sah, 1996). This sAHP was also
insensitive (Fig. 7B) to either norepinephrine (NE) (10 µM; n = 5), or the cholinergic agonist carbachol (10 µM; n = 3), both known
modulators of calcium-dependent sAHPs (Nicoll, 1988). We were able to
block this sAHP, however, by adding the sodium channel blocker
tetrodotoxin (1 µM; n = 7) (Fig.
7C) (Kubota and Saito, 1991). This result is consistent with
the hypothesis that the sAHP present in HVc neurons is generated by
sodium-dependent activation of a potassium conductance (Kubota and
Saito, 1991), although other possibilities cannot be excluded. Unfortunately, because TTX would block both sAHP and synaptic-mediated events, this pharmacological agent could not be used to block selectively the sAHP contribution to the SH. To circumvent this problem, we attempted to block sodium channels with the intracellular sodium channel blocker QX-314. This drug did block the action potential-mediated sAHP. Unfortunately, QX-314 also blocked
GABAB receptor-mediated inhibition (Andrade, 1991)
(n = 3, data not shown) and could not be used here to
remove the sAHP selectively.
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Figure 7.
Properties of the sAHP in HVc neurons.
A, A direct depolarizing current pulse (0.5-2.0 nA; 1 sec) gave rise to a very slowly decaying sAHP. Such depolarization
typically elicited 30-40 action potentials during the pulse (not
shown). Application of the Ca2+ channel blocker
CdCl2 (100 µM), known to block sAHPs in other systems, had no effect on either the duration or amplitude of the sAHP.
B, Norepinephrine (10 µM), which blocks
the sAHP in other cell types (Madison and Nicoll, 1982), did not affect
the sAHP in HVc. C, Bath application of the sodium
channel blocker tetrodotoxin (TTX) (1 µM) completely blocked the slow phase of the sAHP.
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These results indicate that HVc neurons contain a slow, TTX-sensitive
sAHP with a time course similar to the SH observed after synaptic
stimulation. Although we were unable to block the sAHP selectively, we
exploited its lack of dependence on calcium. We thus further
characterized the SH by separating intrinsic from synaptic components
using sensitivity of synaptic transmitter release to cadmium (see
Results).
Contributions of GABAB receptor activation to the
slow hyperpolarization
Most neurons contain a multiplicity of potassium channels, the
activation of which can lead to hyperpolarization (Nicoll, 1988). In
many cases, activation of GABAB receptors by exogenous application of baclofen causes a hyperpolarization via increased potassium conductance. In hippocampal pyramidal cells, synaptically released GABA acts on GABAB receptors to cause slow IPSPs
that last hundreds of milliseconds (Dutar and Nicoll, 1988). To assess whether HVc neurons are capable of responding to GABAB
receptor activation, we first perfused slices with the
GABAB receptor agonist baclofen (30 µM). Bath
application of this agonist caused a marked hyperpolarization in every
cell examined (Fig. 8A)
(11.0 ± 3.8 mV; n = 14). This hyperpolarization
was associated with a decrease in input resistance, consistent with the
increase in potassium conductance observed in other cell types (Fig.
8B) (Newberry and Nicoll, 1984; Gahwiler and Brown,
1985; Nicoll, 1988). When the membrane potential was returned to
control levels by injection of steady depolarizing current, input
resistance was still reduced (Fig.
8B1,B3), indicating
that the conductance change was not merely secondary to the change in
potential.
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Figure 8.
Effect of the GABAB receptor agonist
baclofen on HVc neurons. A, Bath application of baclofen
(30 µM) caused a reversible hyperpolarization associated
with a decrease in input resistance. Input resistance was monitored by
passing 300 msec current pulses (0.1 nA) every 5-20 sec (see
B1-B4). Input resistance remained decreased even
after the membrane potential was shifted back to the original resting
potential by DC depolarization (+ DC;
B3). These results suggest that baclofen causes an
increase in potassium conductance, a commonly observed effect of
activating GABAB receptors in many other systems.
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In the presence of the GABAB receptor antagonist CGP 35348 (500 µM) (Olpe et al., 1990), baclofen did not
significantly hyperpolarize HVc neurons (0.6 ± 1.9 mV;
n = 7; p > 0.35). In six cells,
responses to baclofen were measured in the presence and absence of CGP
35348. The antagonist reduced the baclofen response by 91 ± 20%
(n = 6). When baclofen was added after washout of CGP
35348, neurons responded with the characteristic hyperpolarization
(Fig. 9) (n = 4/4). These
findings validate baclofen and CGP 35348 as selective GABAB
receptor compounds in this avian system and indicate that HVc neurons
express GABAB receptors coupled to potassium channels.
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Figure 9.
Effect of the GABAB receptor
antagonist CGP 35348 on the hyperpolarizing action of baclofen. To test
the effect of CGP 35348 on HVc neurons, neurons were first subjected to
bath application of baclofen (30 µM) to ensure that
baclofen produced a hyperpolarizing response (left
panel). After a recovery period of 20 min the membrane potential returned to near the original resting potential. In the
presence of CGP 35348 (500 µM), baclofen did not affect
the membrane potential (middle panel). The small
difference in membrane potential between the left and
middle panels was not a common observation. Addition of
baclofen after washout of the antagonist produced a normal
hyperpolarizing response (right panel).
Blank portions of the traces during baclofen addition
indicate time when the membrane potential was returned to the original
resting potential (see Fig. 8). These points were omitted for clarity. All traces were obtained from the same neuron over a period of 1 hr.
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To investigate directly the role of GABAB receptors in
generating the slow synaptic hyperpolarization, we examined the effect of CGP 35348 on the SH elicited in the presence of CNQX, APV, and BMI.
Bath application of CGP 35348 (500 µM) produced quite variable effects (Fig.
10B) ranging from no
effect to nearly complete blockade of the SH (Fig.
10A). The average reduction in peak amplitude of the
SH was 44 ± 27% (n = 19). These results
demonstrate that a substantial component of the SH can be accounted for
by activation of GABAB receptors and suggest that GABA is
able to produce IPSPs that last many seconds. The variable effect of
the GABAB antagonist suggests that GABAB
receptors may contribute a different fraction of the SH in different
neurons.
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Figure 10.
Effect of the GABAB receptor
antagonist CGP 35348 on the stimulus-induced SH. A, A
brief, high-frequency stimulus train (50 pulses at 100 Hz; indicated by
the horizontal bar above the trace) was used to elicit a
long-lasting SH in the presence of CNQX (20 µM), APV (100 µM), and BMI (40 µM). After several stable
stimulation trains (elicited every 2 min), CGP 35348 (500 µM) was added to the mixture of drugs. In this particular
example, addition of the GABAB receptor antagonist blocked
a large portion of the SH. The nature of the remaining
hyperpolarization could have been caused by a synaptically mediated
IPSP or alternatively by an sAHP, because stimulation caused antidromic
firing in this neuron. B, The effect of CGP 35348 on the
SH was quite variable across HVc neurons. This histogram illustrates
that nearly all neurons were affected by addition of the
GABAB receptor antagonist. A large proportion of neurons
(64%) had their SH reduced by >30% (n = 11/17).
|
|
A GABAB receptor-independent IPSP contributes to the
slow hyperpolarization
In many cases, a residual SH resisted blockade by the mixture of
CNQX, APV, BMI, and CGP 35348. In an attempt to block the remaining
synaptically mediated hyperpolarization, we applied a mixture of
receptor antagonists implicated in slow hyperpolarizing responses. The
addition of this mixture, consisting of antagonists to opioid receptors
(naloxone, 500 µM), muscarinic acetylcholine receptors
(atropine, 10 µM), or  2 noradrenergic
receptors (yohimbine, 20 µM) was without effect in
reducing either the magnitude or the time course of the
hyperpolarization (n = 3; data not shown).
To assess the relative contribution of synaptic transmission to this
residual SH, we applied the calcium channel blocker
CdCl2, which blocks transmitter release but not the
sAHP (Fig. 7A). The SH was elicited using our standard
stimulation protocol in the presence of antagonists to glutamate and
GABAA receptors (CNQX, APV, and BMI). After several stable
baseline traces (Fig.
11A), the
GABAB component of the SH was removed by adding CGP 35348 (Fig. 11B). After confirming that the antagonistic
effect of CGP 35348 had stabilized, CdCl2 (100 µM) was added to the pharmacological mixture. The calcium
channel blocker reduced the SH (75 ± 29%; n = 5)
(Fig. 11C), suggesting that a significant portion of the SH
is attributable to a GABAB receptor-independent IPSP. In
some cases, a small, brief, residual hyperpolarization remained after the addition of CdCl2 (Fig. 11C). This
hyperpolarization may have been caused by a calcium-independent sAHP
attributable to stimulus-induced antidromic action potentials and could
be blocked by subsequent addition of TTX (data not shown).
View larger version (12K):
[in this window]
[in a new window]
|
Figure 11.
Contribution to the SH of a GABAB
receptor-independent IPSP. A, Sample traces showing the
presence of an SH in the presence of our standard pharmacological
mixture of CNQX (20 µM), APV (100 µM), and
BMI (40 µM). Stimulus train consisted of 50 pulses at 100 Hz, at the time indicated by the horizontal bar below the trace in
C. B, Addition of CGP 35348 significantly
reduced the magnitude of the SH. C, To investigate the
nature of the remaining SH, the inorganic calcium channel blocker
CdCl2 (100 µM) was added to block all
synaptic transmission. Addition of CdCl2 reduced the
response to electrical stimulation. The small remaining
hyperpolarization was caused by a calcium-insensitive sAHP produced by
stimulation-induced antidromic action potentials. In this particular
neuron, stimulation caused 38-40 action potentials. All records are
from the same cell.
|
|
| |
DISCUSSION |
We have described an unusually slow, activity-induced
hyperpolarization in neurons of nucleus HVc in the adult zebra finch. At least three components contribute to the SH to varying degrees: (1)
an afterhyperpolarization intrinsic to the neuron recorded, (2) a
synaptically induced, GABAB receptor-mediated response, and
(3) an unidentified slow IPSP. All three components appear to depend on
increased potassium conductance and individually or collectively may
play an important role in gating information flow in the song
system.
Mechanism of slow hyperpolarization
Intrinsic cell properties
A component of the SH described here is a slow
afterhyperpolarization (sAHP) caused by action potentials evoked during
stimulation in HVc. These action potentials were probably evoked
antidromically by stimulation of the extensive axonal ramifications of
HVc neurons within the nucleus (Katz and Gurney, 1981; Nottebohm et
al., 1982; Fortune and Margoliash, 1995). Although sAHPs are observed
in most neurons studied, the sAHP observed in HVc appears to differ from those observed in most other systems (for review, see Sah, 1996).
Kubota and Saito (1991) used multiple trains of action potentials to
elicit an sAHP in HVc neurons having a time course similar to or longer
than that of sAHPs studied in other systems. The sAHP in HVc is calcium
independent and requires Na+ influx. We have
confirmed these findings and shown that the HVc sAHP also differs from
other sAHPs, including one other known example of sodium-dependent sAHP
(Schwindt et al., 1989), in its apparent insensitivity to modulation by
neurotransmitters such as norepinephrine or acetylcholine (Nicoll,
1988; Foehring et al., 1989).
Although the sAHP component of the SH described here may be a
consequence of our stimulation paradigm, physiological firing rates (Yu
and Margoliash, 1996) could produce a similar sAHP. Slow AHPs in
several neuronal types mediate spike-frequency accommodation (Madison
and Nicoll, 1984; Sah, 1996) and may influence stimulus-induced spike
timing (Hu, 1995). The particularly long time course of the sAHP
observed in HVc neurons (typically 1-5 sec for a train of 30-50
action potentials) suggests that it may help modulate neural activity
during singing.
Synaptic properties
Although we could not block the sAHP component of the SH
selectively, we have shown that one or more slow synaptic events contribute to the SH. In several cases, we were able to elicit a large
SH in the complete absence of antidromic action potentials (Fig.
2A), indicating that the SH can be caused exclusively
by long-lasting synaptic mechanisms. In addition, when antidromic action potentials were present, a substantial proportion of the SH
could be blocked by the calcium channel blocker CdCl2.
Because cadmium blocks Ca2+-dependent transmitter
release and leaves the sAHP intact (Kubota and Saito, 1991; present
results), these manipulations indicate that a synaptic component
contributes to the SH, even when it is accompanied by antidromic action
potentials.
The SH observed here, which lasted up to 20 sec, is unusually long in
duration. This slow time course is most likely caused by slow
transmitter action, but if it is caused by sustained release of a
short-lasting transmitter, intermediary neurons would need to continue
firing after stimulation. Such neurons were never recorded in this
study, and such postulated excitation would need to persist during
blockade of ionotropic glutamate receptors. Alternatively, a circuit
consisting of two mutually inhibitory neuronal populations could show
prolonged activity (Cropper and Weiss, 1996). Such a scenario might be
expected to cause rhythmic bursts of inhibition in the recorded cell.
We did not observe oscillatory inhibition, however. Few IPSPs lasting
seconds have been described. In most cases these appear to be mediated
by serotonin (Pan et al., 1989), norepinephrine (Egan et al., 1983), or
acetylcholine (Dodd and Horn, 1983). Neuropeptides, although not
directly shown to produce IPSPs, have been shown to hyperpolarize
neurons in the CNS and may act as transmitters for slow IPSPs (Nicoll
et al., 1990).
The CGP 35348-sensitive component of the SH lasts up to 20 sec and
appears to require GABAB receptor activation. Although GABAB receptors typically cause IPSPs lasting only a few
hundred milliseconds (Alger, 1984; Newberry and Nicoll, 1984; Dutar and Nicoll, 1988; Nicoll et al., 1990), they have been shown to mediate a
tetanus-induced heterosynaptic presynaptic inhibition in the hippocampus (Isaacson et al., 1993). Because tetanic stimulation can
also cause hyperpolarization in hippocampal pyramidal neurons lasting
several seconds (Cole and Nicoll, 1984, their Fig. 4), these results
suggest that GABAB receptors may cause slow inhibitory synaptic events lasting many seconds. However, repetitive stimulation can also cause depression of GABAB receptor-mediated
responses. The long duration of inhibition observed here may reflect
the stimulation paradigm or an unusually slow action of GABA on HVc neurons, possibly attributable to slow GABA uptake or a long-lasting second messenger system.
In many instances, the addition of the GABAB-receptor
antagonist CGP 35348 only partially blocked the SH. By blocking
calcium-dependent synaptic transmission with CdCl2,
without affecting the sAHP, we were able to show that this residual
hyperpolarization consists of a non-GABAB IPSP. The
transmitter and receptor mediating this synaptic component remain
elusive, because blockade of muscarinic (atropine), 2
noradrenergic (yohimbine), or opioid (naloxone) receptors failed to
block the IPSP. Further mechanistic analysis of this IPSP is clearly
required.
Role of slow hyperpolarization in the song system
Blockade of excitatory transmission by CNQX and APV
consistently attenuated or abolished the SH, indicating that a
significant portion of the hyperpolarization was generated by neurons
intrinsic to HVc that were synaptically excited by our stimulus.
However, failure of these drugs to block the SH completely or change
its slow time course suggests that monosynaptic inhibitory processes contribute to the observed SH. In this study, we cannot distinguish between monosynaptic IPSPs produced by intrinsic HVc neurons and connections extrinsic to HVc. Such extrinsic inputs to HVc could arise
from a number of nuclei, including the thalamic nucleus uvaeformis
(Uva) (Nottebohm et al., 1982), the forebrain medial portion of the
magnocellular nucleus of the anterior neostriatum (M-MAN) and nucleus
interfacialis (NIf) (Nottebohm et al., 1982), the HVc "shelf"
(Vates et al., 1996), and possibly the field L complex (Fortune and
Margoliash, 1995). Because the physiological nature of these inputs is
not known, these connections could provide the excitatory input
sufficient to activate inhibitory neurons within HVc, inhibit HVc
neurons directly, or provide a mixed excitatory/inhibitory input. The
connection from Uva, and possibly NIf (Fig. 1), may be of particular
interest in the context of inhibition of auditory responses during
singing, because stimulation of Uva has been reported to cause
long-lasting inhibition of auditory responses in HVc (Williams,
1989).
The SH often consisted of a combination of sAHP,
GABAB-receptor mediated IPSP, and a third unidentified
IPSP. The relative contribution of these components to the SH was quite
variable. In the present study, we did not attempt to estimate
quantitatively the relative contributions to the SH made by the various
component mechanisms, because these values likely depend on the details of electrode placement as well as on the class of neuron being recorded
and the connections it receives. Identification of the afferent types
being stimulated remains challenging because of the confluence from
multiple sources. A description of the neuronal properties in HVc may
yield interesting insight into the role of this slow inhibition.
Nucleus HVc sends out two major projections, to area X and to nucleus
robustus archistriatalis (RA) (Nottebohm et al., 1982), originating
from separate neuronal populations (Katz and Gurney, 1981; Lewicki,
1996) that may be functionally distinct (Kimpo and Doupe, 1997). The
X-projecting neurons have auditory responses (Katz and Gurney, 1981;
Lewicki, 1996). We have shown here that only a portion (~60%) of all
neurons recorded in HVc exhibit an SH after stimulation within HVc.
Recent results (Dutar and Perkel, 1997) suggest that only X-projecting
HVc neurons have the SH, providing a clear physiological difference
between these neuronal populations.
The SH observed in this study may contribute to generating song
selectivity of auditory responses (Margoliash, 1983). Song-selective neurons, which respond most strongly to playback of the bird's own
song, were found to become most hyperpolarized during presentation of
their preferred stimulus (Lewicki, 1996; Lewicki and Konishi, 1995).
This hyperpolarization was interrupted by short, precisely timed bursts
of action potentials during specific segments of the song. The
hyperpolarization, as well as the bursts, were absent during
presentation of less favorable auditory stimuli. Hyperpolarization may
permit deinactivation of voltage-dependent conductances, which are
thought to cause bursting behavior in certain systems (Crunelli and
Leresche, 1991; von Krosigk et al., 1993). These hyperpolarizations, which can be caused by either extrinsic (e.g., GABAB in the
lateral geniculate nucleus) (Crunelli and Leresche, 1991) or intrinsic mechanisms (e.g., sAHP in auditory thalamus) (Hu, 1995), may permit bursts of action potentials and thus provide more precise information than single action potentials (for review, see Lisman, 1996). Long-lasting, stimulus-induced hyperpolarizations may thus play a
crucial role in enhancing signal-to-noise ratio by suppressing background noise, and responses to weak inputs, while allowing strong
stimuli to produce precisely timed bursts of action potentials (Karlsson et al., 1990; Mainen and Sejnowski, 1995).
The SH could also contribute to the long-lasting inhibition of auditory
responses observed during and after singing (McCasland and Konishi,
1981). Because HVc acts as a gateway for auditory information flow into
the song system and because song learning requires auditory feedback,
inhibition of auditory responses during singing could be regulated
during song learning. It will be critical to understand whether and how
inhibition in HVc modulates the flow of auditory information into the
rest of the song system during different stages of song acquisition.
Identification of the cellular basis of this inhibition as well as its
development during song learning will illuminate a pivotal aspect of
auditory-motor integration.
| |
FOOTNOTES |
Received Sept. 4, 1997; revised Nov. 17, 1997; accepted Nov. 19, 1997.
This work was supported by a Helen Hay Whitney Postdoctoral Fellowship
to D.J.P., as well as grants from National Institutes of Health (NRSA
DC00125 and RO3DC03041 to M.F.S. and RO3 DC02477 to D.J.P.). We thank
Drs. Gilles Laurent, Anthony Leonardo, and Mark Konishi, as well as
members of the Perkel laboratory, for helpful comments on this
manuscript. We also thank Mark Konishi, in whose laboratory many of
these experiments were performed, for his valuable support and
advice.
Correspondence should be addressed to David J. Perkel, Department of
Neuroscience, 215 Stemmler Hall, University of Pennsylvania, Philadelphia, PA 19104-6074.
| |
REFERENCES |
-
Alger BE
(1984)
Characterization of a slow hyperpolarizing synaptic potential in rat hippocampal pyramidal cells in vitro.
J Neurophysiol
52:892-910[Abstract/Free Full Text].
-
Alger BE,
Nicoll RA
(1982)
Pharmacological evidence for two kinds of GABA receptors on rat hippocampal pyramidal cells studied in vitro.
J Physiol (Lond)
328:125-141[Abstract/Free Full Text].
-
Allerton CA,
Boden PR,
Hill RG
(1989)
Actions of the GABAB agonist ()-baclofen on neurones in deep dorsal horn of the rat spinal cord in vitro.
Br J Pharmacol
96:29-38[Web of Science][Medline].
-
Andersen P,
Dingledine R,
Gjerstad L,
Langmoen IA,
Laursen AM
(1980)
Two different responses of hippocampal pyramidal cells to application of gamma-aminobutyric acid.
J Physiol (Lond)
305:279-296[Abstract/Free Full Text].
-
Andrade R
(1991)
Blockade of neurotransmitter-activated K+ conductance by QX-314 in the rat hippocampus.
Eur J Pharmacol
199:259-262[Web of Science][Medline].
-
Brenowitz EA,
Margoliash D,
Nordeen KW
(1997)
An introduction to birdsong and the avian song system.
J Neurobiol
33:495-500[Web of Science][Medline].
-
Cole AE,
Nicoll RA
(1984)
Characterization of a slow cholinergic post-synaptic potential recorded in vitro from rat hippocampal pyramidal cells.
J Physiol (Lond)
352:173-188[Abstract/Free Full Text].
-
Connors BW,
Malenka RC,
Silva LR
(1988)
Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor-mediated responses in neocortex of rat and cat.
J Physiol (Lond)
406:443-468[Abstract/Free Full Text].
-
Cropper EC,
Weiss KR
(1996)
Synaptic mechanisms in invertebrate pattern generation.
Curr Opin Neurobiol
6:833-841[Web of Science][Medline].
-
Crunelli V,
Leresche N
(1991)
A role for GABAB receptors in excitation and inhibition of thalamocortical cells.
Trends Neurosci
14:16-21[Web of Science][Medline].
-
Curtis DR,
Duggan AW,
Felix D,
Johnston GAR
(1970)
Bicuculline and central inhibition.
Nature
226:1222-1224[Medline].
-
Davies J,
Francis AA,
Jones AW,
Watkins JC
(1981)
2-Amino-5-phosphono-valerate (2APV), a potent and selective antagonist of amino acid induced and synaptic excitation.
Neurosci Lett
21:77-82[Web of Science][Medline].
-
Dodd J,
Horn JP
(1983)
Muscarinic inhibition of sympathetic C neurones in the bullfrog.
J Physiol (Lond)
334:271-291[Abstract/Free Full Text].
-
Doupe AJ
(1993)
A neural circuit specialized for vocal learning.
Curr Opin Neurobiol
3:104-111[Medline].
-
Doupe AJ,
Konishi M
(1991)
Song-selective auditory circuits in the vocal control system of the zebra finch.
Proc Natl Acad Sci USA
88:11339-11343[Abstract/Free Full Text].
-
Dutar P,
Nicoll RA
(1988)
A physiological role for GABAB receptors in the central nervous system.
Nature
332:156-158[Medline].
-
Dutar P,
Perkel DJ
(1997)
Distinct functional properties of HVc neurons projecting to area X and to RA in the zebra finch.
Soc Neurosci Abstr
23:246.
-
Egan TM,
Henderson G,
North RA,
Williams JT
(1983)
Noradrenaline-mediated synaptic inhibition in rat locus coeruleus neurones.
J Physiol (Lond)
345:477-488[Abstract/Free Full Text].
-
Foehring RC,
Schwindt PC,
Crill WE
(1989)
Norepinephrine selectively reduces slow Ca++ and Na+ dependent K+currents in cat neocortical neurons.
J Neurophysiol
62:245-256.
-
Fortune ES,
Margoliash D
(1995)
Parallel pathways and convergence onto HVc and adjacent neostriatum of adult male zebra finches (Taeniopygia guttata).
J Comp Neurol
360:413-441[Web of Science][Medline].
-
Gahwiler BH,
Brown DA
(1985)
GABAB-receptor activated K+ current in voltage-clamped CA3 pyramidal cells in hippocampus.
Proc Natl Acad Sci USA
82:1558-1562[Abstract/Free Full Text].
-
Honoré T,
Davies SN,
Drejer J,
Fletcher EJ,
Jacobsen P,
Nielsen FE
(1988)
Quinoxaline-diones: potent competitive non-NMDA glutamate receptor antagonists.
Science
241:701-703[Abstract/Free Full Text].
-
Hu B
(1995)
Cellular basis of temporal synaptic signalling: an in vitro electrophysiological study in rat auditory thalamus.
J Physiol (Lond)
483:167-182[Abstract/Free Full Text].
-
Isaacson JS,
Solis JM,
Nicoll RA
(1993)
Local and diffuse synaptic actions of GABA in the hippocampus.
Neuron
10:165-175[Web of Science][Medline].
-
Jan LY,
Jan YN
(1982)
Peptidergic transmission in sympathetic ganglia of the frog.
J Physiol (Lond)
327:219-246[Abstract/Free Full Text].
-
Karlsson G,
Schmutz M,
Kolb C,
Bittiger H,
Olpe HR
(1990)
GABAB receptors and experimental models of epilepsy.
In: GABAB receptors in mammalian function (Bowery NG,
Bittinger H,
Olpe HR,
eds), pp 349-365. New York: Wiley.
-
Katz LC,
Gurney ME
(1981)
Auditory responses in the zebra finch's motor system for song.
Brain Res
221:192-197[Web of Science][Medline].
-
Kimpo RR,
Doupe AJ
(1997)
FOS is induced by singing in distinct neuronal populations in a motor network.
Neuron
18:315-325[Web of Science][Medline].
-
Kubota M,
Saito N
(1991)
Sodium- and calcium-dependent conductances of neurones in the zebra finch hyperstriatum ventrale pars caudale in vitro.
J Physiol (Lond)
440:131-142[Abstract/Free Full Text].
-
Lewicki MS
(1996)
Intracellular characterization of song-specific neurons in the zebra finch auditory forebrain.
J Neurosci
15:5854-5863.
-
Lewicki MS,
Konishi M
(1995)
Mechanisms underlying the sensitivity of songbird forebrain neurons to temporal order.
Proc Natl Acad Sci USA
92:5582-5586[Abstract/Free Full Text].
-
Lisman JE
(1996)
Bursts as a unit of neural information: making unreliable synapses reliable.
Trends Neurosci
20:38-43.
-
Madison DV,
Nicoll RA
(1982)
Noradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus.
Nature
299:636-638[Medline].
-
Madison DV,
Nicoll RA
(1984)
Control of the repetitive discharge of rat CA1 pyramidal neurons in vitro.
J Physiol (Lond)
354:319-331[Abstract/Free Full Text].
-
Mainen ZF,
Sejnowski TJ
(1995)
Reliability of spike timing in neocortical neurons.
Science
268:1503-1506[Abstract/Free Full Text].
-
Margoliash D
(1983)
Acoustic parameters underlying the responses of song-specific neurons in the white-crowned sparrow.
J Neurosci
3:1039-1057[Abstract].
-
Margoliash D,
Konishi M
(1985)
Auditory representation of autogenous song in the song system of white-crowned sparrows.
Proc Natl Acad Sci USA
82:5997-6000[Abstract/Free Full Text].
-
McCasland JS
(1987)
Neuronal control of bird song production.
J Neurosci
7:23-39[Abstract].
-
McCasland JS,
Konishi M
(1981)
Interactions between auditory and motor activities in an avian song control nucleus.
Proc Natl Acad Sci USA
78:7815-7819[Abstract/Free Full Text].
-
Mooney R
(1992)
Synaptic basis for developmental plasticity in a birdsong nucleus.
J Neurosci
12:2464-2477[Abstract].
-
Newberry NR,
Nicoll RA
(1984)
A bicuculline-resistant inhibitory post-synaptic potential in rat hippocampal pyramidal cells in vitro.
J Physiol (Lond)
348:239-254[Abstract/Free Full Text].
-
Nicoll RA
(1988)
The coupling of neurotransmitter receptors to ion channels in the brain.
Science
241:545-551[Abstract/Free Full Text].
-
Nicoll RA,
Malenka RA,
Kauer JA
(1990)
Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system.
Physiol Rev
70:513-565[Free Full Text].
-
Nixdorf BE,
Davis SS,
DeVoogd TJ
(1989)
Morphology of Golgi-impregnated neurons in hyperstriatum ventralis, pars caudalis in adult male and female canaries.
J Comp Neurol
284:337-349[Web of Science][Medline].
-
Nottebohm F,
Stokes TM,
Leonard C
(1976)
Central control of song in the canary, Serinus canarius.
J Comp Neurol
165:457-486[Web of Science][Medline].
-
Nottebohm F,
Kelley DB,
Paton JA
(1982)
Connections of vocal control nuclei in the canary telencephalon.
J Comp Neurol
207:344-357[Web of Science][Medline].
-
Olpe H,
Karlsson G,
Pozza MF,
Brugger F,
Steinmann M,
Van Riezen H,
Fagg G,
Hall RG,
Froestl W,
Bittiger H
(1990)
CGP35348: a centrally active blocker of GABAB receptors.
Eur J Pharmacol
187:27-38[Web of Science][Medline].
-
Pan ZZ,
Colmers WF,
Williams JT
(1989)
5-HT-mediated synaptic potentials in the dorsal raphe nucleus: interactions with excitatory amino acid and GABA transmission.
J Neurophysiol
62:481-486[Abstract/Free Full Text].
-
Pepper CM,
Henderson G
(1980)
Opiates and opioid peptides hyperpolarize locus coeruleus neurons in vitro.
Science
208:394-396.
-
Perkel DJ,
Nicoll RA
(1993)
Evidence for all-or-none regulation of neurotransmitter release: implications for long-term potentiation.
J Physiol (Lond)
471:481-500[Abstract/Free Full Text].
-
Pittman QJ,
Siggins GR
(1981)
Somatostatin hyperpolarizes hippocampal pyramidal cells in vitro.
Brain Res
221:402-408[Web of Science][Medline].
-
Sah P
(1996)
Calcium-activated K currents in neurones: types, physiological roles and modulation.
Trends Neurosci
19:150-154[Web of Science][Medline].
-
Schwindt PC,
Spain WJ,
Crill WE
(1989)
Long-lasting reduction of excitability by a sodium-dependent potassium current in cat neocortical neurons.
J Neurophysiol
61:233-244[Abstract/Free Full Text].
-
Staley KJ,
Soldo BL,
Proctor WR
(1995)
Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors.
Science
269:977-981[Abstract/Free Full Text].
-
Vates GE,
Broome BM,
Mello CV,
Nottebohm F
(1996)
Auditory pathways of caudal telencephalon and their relation to the song system of adult male zebra finches (Taeniopygia guttata).
J Comp Neurol
366:613-642[Web of Science][Medline].
-
Vicario DS,
Yohay KH
(1993)
Song-selective auditory input to a forebrain vocal control nucleus in the zebra finch.
J Neurobiol
24:488-505[Web of Science][Medline].
-
von Krosigk M,
Bal T,
McCormick DA
(1993)
Cellular mechanisms of a synchronized oscillation in the thalamus.
Science
261:361-364[Abstract/Free Full Text].
-
Vu E,
Lewicki MS
(1994)
Intrinsic interactions between zebra finch HVc neurons involve NMDA-receptor activation.
Soc Neurosci Abstr
20:166.
-
Vu ET,
Mazurek ME,
Kuo YC
(1994)
Identification of a forebrain motor programming network for the learned song of zebra finches.
J Neurosci
14:6924-6934[Abstract].
-
Wagner EJ,
Moore KE,
Lookingland KJ
(1994)
Neurochemical evidence that AMPA receptor-mediated tonic inhibition of hypothalamic dopaminergic-neurons occurs via activation of inhibitory interneurons.
Brain Res
660:319-322[Web of Science][Medline].
-
Williams H
(1989)
Multiple representations and auditory-motor interactions in the avian song system.
Ann NY Acad Sci
563:148-164[Web of Science].
-
Williams JT,
Egan TM,
North RA
(1982)
Enkephalin opens potassium channels on mammalian central neurons.
Nature
299:74-77[Medline].
-
Yu AC,
Margoliash D
(1996)
Temporal hierarchical control of singing in birds.
Science
273:1871-1875[Abstract/Free Full Text].
Copyright © 1998 Society for Neuroscience 0270-6474/98/183895-10$05.00/0
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|
R. Mooney and J. F. Prather
The HVC Microcircuit: The Synaptic Basis for Interactions between Song Motor and Vocal Plasticity Pathways
J. Neurosci.,
February 23, 2005;
25(8):
1952 - 1964.
[Abstract]
[Full Text]
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M. F. Schmidt
Pattern of Interhemispheric Synchronization in HVc During Singing Correlates With Key Transitions in the Song Pattern
J Neurophysiol,
December 1, 2003;
90(6):
3931 - 3949.
[Abstract]
[Full Text]
[PDF]
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P. Dutar, J. J. Petrozzino, H. M. Vu, M. F. Schmidt, and D. J. Perkel
Slow Synaptic Inhibition Mediated by Metabotropic Glutamate Receptor Activation of GIRK Channels
J Neurophysiol,
November 1, 2000;
84(5):
2284 - 2290.
[Abstract]
[Full Text]
[PDF]
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T. W. Troyer and A. J. Doupe
An Associational Model of Birdsong Sensorimotor Learning I. Efference Copy and the Learning of Song Syllables
J Neurophysiol,
September 1, 2000;
84(3):
1204 - 1223.
[Abstract]
[Full Text]
[PDF]
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M. Luo and D. J. Perkel
A GABAergic, Strongly Inhibitory Projection to a Thalamic Nucleus in the Zebra Finch Song System
J. Neurosci.,
August 1, 1999;
19(15):
6700 - 6711.
[Abstract]
[Full Text]
[PDF]
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J. E. Spiro, M. B. Dalva, and R. Mooney
Long-Range Inhibition Within the Zebra Finch Song Nucleus RA Can Coordinate the Firing of Multiple Projection Neurons
J Neurophysiol,
June 1, 1999;
81(6):
3007 - 3020.
[Abstract]
[Full Text]
[PDF]
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P. Dutar, H. M. Vu, and D. J. Perkel
Multiple Cell Types Distinguished by Physiological, Pharmacological, and Anatomic Properties in Nucleus HVc of the Adult Zebra Finch
J Neurophysiol,
October 1, 1998;
80(4):
1828 - 1838.
[Abstract]
[Full Text]
[PDF]
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Top
Abstract
Introduction
