 |
 Previous Article | Next Article 
The Journal of Neuroscience, August 1, 1999, 19(15):6694-6699
Glutamate Inhibits Thalamic Reticular Neurons
Charles L.
Cox and
S. Murray
Sherman
Department of Neurobiology, State University of New York, Stony
Brook, New York 11794-5230
 |
ABSTRACT |
Activation of metabotropic glutamate receptors (mGluRs) can result
in long-lasting modulation of neuronal excitability. Multiple mGluR
subtypes are localized within the rat thalamic reticular nucleus (TRN),
and we have examined the effects of activating these different receptor
subtypes on the excitability of these neurons using an in
vitro slice preparation. Typical of most mGluR-sensitive preparations, the general mGluR agonist,
(±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid
(ACPD) produced a robust, long-lasting excitatory response. Surprisingly, ACPD produced a membrane hyperpolarization in some neurons. Using selective mGluR agonists, we found that activation of
group II mGluRs produces the hyperpolarization, whereas the depolarization is mediated by group I mGluRs. While the polarity of the
postsynaptic response (hyperpolarization vs depolarization) was
dependent on the mGluR subtype activated, both actions appear to result
from modification of a linear K+ conductance. The
inhibitory action of Glutamate, via group II mGluRs, provides an avenue
for a disinhibitory effect that could have interesting consequences
upon a well-investigated, model neuronal circuit, turning its assumed
functional role upside down.
Key words:
thalamus; metabotropic glutamate receptors; thalamic
reticular nucleus; inhibition; thalamocortical
| |
INTRODUCTION |
The thalamic reticular nucleus (TRN)
consists of a thin layer of GABA-containing neurons that forms a
shell predominantly lateral to the dorsal thalamus (Jones, 1985 ). All
axons communicating between thalamus and cortex in both directions pass
through and innervate the TRN. Because TRN neurons provide a powerful
inhibitory input to thalamocortical relay cells, they are strategically
situated to influence the responsiveness of thalamic relays (Cox et
al., 1997; Kim et al., 1997; Sanchez-Vives et al., 1997). The activity of TRN neurons has been associated with various functions, including the regulation of receptive field sizes (Lee et al., 1994a,b) and the
generation of synchronized oscillations among thalamic neurons during
certain phases of sleep and forms of epilepsy (Steriade et al., 1986,
1993; Avoli et al., 1990; Buzsáki et al., 1990). Much of the
afferent input to TRN derives from collaterals of both corticothalamic
and thalamocortical axons, which are glutamatergic and thus have been
widely assumed to be purely excitatory. Thus, most views of TRN are
based on the idea that it provides a feedback inhibitory input to
dorsal thalamus (i.e., being excited by glutamatergic relay cell axons
and projecting back to these relay cells) and a feedforward inhibitory
input from cortex (i.e., being excited by glutamatergic corticothalamic
axons and projecting to thalamic relay cells).
Glutamate can activate multiple subtypes of both ionotropic and
metabotropic receptors, primarily leading to EPSPs in the CNS.
Activation of metabotropic glutamate receptors (mGluRs) is of
increasing interest, because such activation through G-protein-coupled, second messenger pathways stereotypically produce long-lasting changes
in neuronal excitability, in contrast to the relatively short-lasting
actions of activating ionotropic glutamate receptors (iGluRs) (Watkins
and Evans, 1981; Conn and Pin, 1997). At least eight subtypes of mGluRs
have been identified, and they are currently differentiated into three
primary groups based on pharmacology, structural homology, and signal
transduction mechanism (Nakanishi, 1992; Conn and Pin, 1997). Different
mGluR subtypes have been associated with a variety of presynaptic and
postsynaptic actions in many CNS regions (Watkins and Evans, 1981;
Collingridge and Lester, 1989; Schoepp and Conn, 1993; Conn and Pin,
1997). Whereas activation of mGluRs usually results in a postsynaptic
excitation (Charpak et al., 1990; Mercuri et al., 1993; Davies et al.,
1995; Eaton and Salt, 1996; Lee and McCormick, 1997; Turner and Salt, 1998), several studies have indicated that mGluR activation may also
produce a postsynaptic inhibitory response (Shirasaki et al., 1994;
Holmes et al., 1996; Fiorillo and Williams, 1998). More specifically,
activation of group II mGluRs produces a postsynaptic inhibitory
response in basolateral amygdala (Holmes et al., 1996). This is of
particular interest, because recent immunohistochemical evidence
suggests that TRN cells possess several distinct types of mGluR (Ohishi
et al., 1993a,b). The presence of group II mGluRs in particular suggest
the possibility of glutamatergic inhibition of TRN cells, thereby
dramatically changing our ideas of the functional circuitry involving
TRN. We sought to test this possibility by pharmacological
investigation of TRN cells in an in vitro thalamic slice preparation.
| |
MATERIALS AND METHODS |
Thalamic slices were prepared as previously described (Cox et
al., 1998). Briefly, young Sprague Dawley rats (P10-P18) were deeply
anesthetized with pentobarbital sodium (50 mg/kg), and the brains were
quickly removed. Tissue slices (300-350 µm) were cut in the
horizontal plane using a vibratome in cold, oxygenated slicing medium
containing (in mM): 2.5 KCl, 1.25 NaH2PO4, 10.0 MgCl2,
0.5 CaCl2, 26.0 NaHCO3, 11.0, glucose and 234.0 sucrose. Slices were transferred to a holding chamber
containing oxygenated (5% CO2 and 95%
O2) physiological solution that contained (in mM): 126.0 NaCl, 2.5 KCl, 1.25 NaH2PO4, 2.0 MgCl2,
2.0 CaCl2, 26.0 NaHCO3, and 10.0 glucose for at least 1 hr before recording. Individual slices were then
transferred to a recording chamber maintained at 30 ± 1°C, and
oxygenated physiological saline was continuously superfused at a rate
of 3 ml/min.
Whole-cell recordings were obtained from visually identified thalamic
reticular neurons with differential interference contrast optics and
infrared video microscopy. An Axoclamp2A amplifier (Axon Instruments,
Foster City, CA) was used in bridge mode for voltage recordings and
discontinuous single electrode voltage-clamp mode for current
recordings. In voltage-clamp recordings, switching frequencies ranged
from 3 to 4 kHz with a gain of 300-800 pA/mV, and the headstage was
continually monitored to ensure that the current transient had
completely decayed before voltage measurements. Voltage-clamp
recordings were limited to neurons that had a stable access resistance
of <25 M . No correction for liquid junction potential has been made
to the voltage measurements. Recording pipettes were pulled from 1.5 mm
outer diameter capillary tubing and filled with the following
intracellular solution (in mM): 117 K gluconate, 13 KCl,
1.0 MgCl2, 0.07 CaCl2, 0.1 EGTA, 10.0 HEPES, 2.0 Na2-ATP, and 0.4 Na-GTP. In some experiments, Cs-gluconate and CsCl were substituted for
K-gluconate and KCl, respectively, to suppress
K+-mediated conductances. The pH of the solution was
adjusted to 7.3 using KOH or CsOH, and osmolality was adjusted to 280 mosm with distilled water.
Concentrated stock solutions of pharmacological agents were prepared in
either distilled water or 0.1 M NaOH and diluted in physiological solution to final concentrations before use. Agonists were applied by injecting a bolus into the flow line of the chamber over 20-60 sec using a motorized syringe pump. Based on the rate of
agonist injection and chamber perfusion, the final bath concentration of agonists were estimated to be approximately one-fourth of the concentration introduced in the flow line (Cox et al., 1995). Concentrations listed in the text are the concentrations of the injected agent before the fourfold dilution in the bath. Antagonists were diluted to a final concentration from concentrated stocks and
bath-applied. All compounds were purchased from Tocris Cookson (St.
Louis, MO) or Sigma (St. Louis, MO).
| |
RESULTS |
Current-clamp recordings of rat TRN neurons associated with the
ventrobasal complex (the primary somatosensory thalamic relay) revealed
that the general mGluR agonist
(±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD;
125-250 µM) produced a long-lasting robust
depolarization (mean ± SD; 9.4 ± 5.8 mV; n = 11) that could result in action potential discharge (Fig.
1A). The ACPD-mediated
depolarization was associated with an increase in input resistance and
persisted in the presence of tetrodotoxin (TTX; 1 µM),
suggesting that activation of postsynaptic mGluRs on the recorded cell
underlies the alteration in membrane potential (Fig.
1A). Given that ACPD is a general agonist for both
group I and II mGluR subtypes, specific mGluR agonists were then tested
on TRN neurons. The selective group I agonist
(RS)-3,5-dihroxyphenylglycine (DHPG; 250-500
µM) with and without TTX (1 µM) also
produced a strong depolarization with an increased input resistance
similar to that seen with ACPD (Fig. 1B). At these
concentrations (250-500 µM), suprathreshold
depolarizations were commonly observed.
View larger version (36K):
[in this window]
[in a new window]
|
Figure 1.
Activation of mGluRs alters excitability of a TRN
neuron. These examples reflect current-clamp recording.
A, Control, ACPD (125 µM,
thick line under recording) produces a long-lasting
membrane depolarization leading to spike discharge (spikes truncated).
The depolarization is interrupted for 20-30 sec by current injection
to repolarize the membrane to the pre-ACPD level ( 70 mV), thereby
controlling for any voltage-dependent effects while comparing pre-ACPD
and post-ACPD input resistance. During the depolarization, there is an
increase in baseline activity, presumably representing EPSPs
originating from suprathreshold excitation by the ACPD of afferent
glutamatergic inputs (e.g., from ventrobasal relay cells that are
generally connected the TRN neurons in these slice preparation).
A, TTX, With addition of TTX (1 µM), the ACPD-mediated depolarization persists, but the
increase in baseline activity is eliminated as are, of course, the
action potentials. In both Control and
TTX, the increased amplitude of membrane responses to
the hyperpolarizing current steps indicate an increase in neuronal
input resistance. B, Control, In a
different TRN neuron, the group I mGluR agonist DHPG (250 µM) produces a robust depolarization, evoking action
potentials (spikes truncated) as well as a robust increase in baseline
activity. B, TTX, The DHPG depolarization
persists in the presence of TTX (1 µM). As in
A, the larger voltage responses to hyperpolarizing
current steps after the membrane potential is manually returned to the
pre-DHPG level of 74 mV indicate a decrease in input resistance.
C, Control, The selective group II mGluR
agonist S3-C4HPG (500 µM) produces a small membrane
hyperpolarization from the initial membrane potential of 65 mV (the
dashed line serves as a reference to this), and the
responses to current steps indicate a small decrease in neuronal input
resistance in a different TRN neuron. C,
TTX, The S3-C4HPG-mediated hyperpolarization persists in
TTX (1 µM).
|
|
In contrast, the selective group II agonist
S-3-carboxy-4-hydroxyphenylglycine (S3-C4HPG; 500-2000
µM) produced a small amplitude membrane hyperpolarization
in TRN cells (Fig. 1C). This hyperpolarization was observed
in 18 of 26 neurons and had an average peak amplitude of 1.5 ± 0.6 mV (range, 0.9-3.2 mV). It also persisted in TTX (1 µM), suggesting a postsynaptic action (Fig.
1C). We also saw some evidence for a slight decrease in
input resistance during these current-clamp recordings, but the changes
were small, variable, and often unreliable. We thus chose the more
sensitive technique of measuring current responses to ramped command
voltages during voltage-clamp recording to obtain a more reliable
measure of changed input resistance, and this is described below.
Further support of this hyperpolarizing action of group II mGluR
activation was provided by a different agent,
(2S,1'R, 2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG IV), a potent agonist of group II mGluRs that also activates NMDA
receptors. Similar to S3-C4HPG, DCG IV (100 µM) produced an initial hyperpolarization, followed by a robust, AP-5-sensitive depolarization as predicted by the mixed action of this agonist on both
group II mGluRs and NMDA receptors (n = 4; data not shown).
In three neurons, ACPD produced an apparent biphasic action. That is,
in control conditions ACPD produced the typical membrane depolarization
associated with an increased baseline activity (Fig.
2A). However, in TTX (1 µM), ACPD produced an initial relatively brief
hyperpolarization that was followed by a longer lasting depolarization
(Fig. 2A, TTX). Similarly,
voltage-clamp recordings from a different neuron indicate that, in
control conditions, ACPD produced a net inward current as expected by
group I mGluR activation (Fig. 2B). When TTX (1 µM) was added to the preparation for this neuron, ACPD
produced a short-lasting outward current that was followed by a longer
lasting inward current (Fig. 2B, TTX). Furthermore, during the initial outward current
there is an increase in the current response to the ramped voltage
commands (Fig. 2B, downward
deflections) indicative of an increased conductance, and the
opposite is observed during the inward current (decreased membrane
response). These data indicate that both the group I and II
mGluR-mediated responses can occur in the same TRN neurons, and
furthermore they can be elicited by the general mGluR agonist.
View larger version (40K):
[in this window]
[in a new window]
|
Figure 2.
Biphasic actions of ACPD on TRN cells.
A, Control, In control conditions during
current-clamp recording, ACPD (125 µM) produces a
depolarization associated with a large increase in spontaneous
depolarizations (presumed EPSPs), and action potentials are evoked. The
depolarization is interrupted by a manual return of the membrane
voltage to the pre-ACPD level of 63 mV. A,
TTX, With the addition of TTX (1 µM), ACPD
produces an early hyperpolarization with reduced input resistance
followed by a longer lasting depolarization with increased input
resistance. B, Control, In a
voltage-clamp recording from a different neuron, ACPD (125 µM) produces an inward current associated with an
increase in small inward currents, which are presumed EPSCs.
B, TTX, With the addition of TTX (1 µM), ACPD no longer produces an increase in baseline
activity but does evoke an initial outward current followed by a
longer-lasting inward current. See legend to Figure 3 for explanation
of the downward deflections during the voltage-clamp
recording.
|
|
To further investigate the mechanisms underlying the mGluR-mediated
membrane potential changes, voltage-clamp recordings using ramped
voltage commands (50 to 90 mV) were used to quantify alterations in
input conductance. In control conditions, ACPD produced a net inward
current that had an average peak of 67.0 ± 32.0 pA
(n = 10) that persisted in 1 µM TTX (Fig.
3Ai). During the ACPD-induced
inward current, the slope of the current response to the ramped voltage
commands was significantly decreased, reflecting a reduction in input
conductance (p < 0.05; paired Student's
t test; n = 6; Fig. 3Aii). This
decreased conductance averaged 0.69 ± 0.55 nS (range, 0.06-1.49
nS), accounting for a 1-15% reduction in resting conductance. The
ACPD-altered current appears linear over the tested voltage range (50
to 90 mV) and reversed near EK,
indicating that ACPD likely decreases a Kleak conductance (Fig. 3Aiii). Similarly, the group I agonist DHPG also
produced a TTX-insensitive inward current (Fig. 3Bi)
associated with a significant reduction of a conductance that reverses
near EK (Fig. 3Bii,iii;
p < 0.05; n = 5).
View larger version (21K):
[in this window]
[in a new window]
|
Figure 3.
Activation of different mGluR subtypes during
voltage-clamp recording in the presence of TTX (1 µM)
differentially alters K+ conductances.
Ai, The general mGluR agonist ACPD (125 µM) produces an inward current associated with a decrease in amplitude of
the downward deflections. These deflections are current responses to
ramped voltage commands (50 to 90 mV, 2 sec duration). Thus, the
reduced amplitude of the deflections reflects an increase in input
resistance. Aii, Expanded traces of the averaged
recorded current responses (I; n = 5) versus the ramped voltage commands before (Pre-drug,
thin line) and during (ACPD, thick
line) the peak ACPD response. In response to ACPD, there is an
inward shift of the holding current (indicative of the inward current)
and decreased slope of the membrane response, indicating a decreased
conductance. Aiii, Difference between the pre-drug and
ACPD traces in Aii, thereby showing the ACPD-mediated
current response. The extrapolated reversal potential of this current
is 90 mV. Bi, From a different TRN neuron, the
specific group I mGluR agonist DHPG (250 µM) produces an
inward current similar to that seen in Ai with ACPD.
Bii, Average of five responses as in Aiii
to the ramped voltage commands before (Pre-drug) and
during (DHPG) the peak agonist response. DHPG produces a
decreased slope of the current response, as in Aii.
Biii, The extrapolated reversal potential of the DHPG-mediated
current was 94 mV. Ci, From the TRN neuron in Figure
1C, the selective group II mGluR agonist S3-C4HPG (500 µM) produces a small outward current. The downward
deflections that are membrane responses to voltage ramps are truncated
in this illustration. Cii, Average of five responses as
in Aiii to the ramped voltage commands before
(Pre-drug) during (S3-C4HPG) the peak
agonist response. Note the increased slope of the response to S3-C4HPG.
Ciii, The extrapolated reversal potential of the
increased current was 85 mV.
|
|
In contrast, the selective group II mGluR agonist S3-C4HPG produced a
TTX-insensitive outward current (Fig. 3Ci; 20.2 ± 17.0 pA; n = 13; range, 7-73 pA). The S3-C4HPG outward
current was associated with a significant increase in resting membrane
conductance (p < 0.05; n = 10;
Fig. 3Cii). This increased conductance averaged 0.48 ± 0.49 nS (range, 0.07-1.74 nS) accounting for a 1-18% increase in
resting conductance. This current appears linear and also reverses near
EK, suggesting group II mGluR activation
increases a Kleak conductance (Fig. 3Ciii).
Thus, although our data are consistent with the possibility that
activation of group I or II mGluRs alters an apparent, single linear
K+ conductance, we do not have the data necessary to
determine whether this is a single conductance involving one group of
K+ channels or multiple conductances and
K+ channel types. Nonetheless, our experiments
indicate that the direction of the conductance change (increase or
decrease) is dependent on the mGluR subtype activated.
The role of mGluRs mediating this hyperpolarization was further
supported by the reversible antagonism of the S3-C4HPG-mediated hyperpolarization by the general mGluR antagonist
(RS)- -methyl-4-carboxyphenylglycine (MCPG), as
illustrated in Figure
4A (n = 3). In addition, because the voltage-clamp recordings suggest that
activation of either group I or II mGluRs alters K+
conductances, Cs+-containing recording pipettes were
used to suppress K+ currents. As Figure
4B illustrates, the ACPD-mediated inward current was
absent or very small in these recording conditions (n = 6). Furthermore, the S3-C4HPG-induced outward current was also absent
(n = 3).
View larger version (39K):
[in this window]
[in a new window]
|
Figure 4.
A, Current-clamp recording showing
attenuation by mGluR antagonists of group II mGluR agonist-mediated
hyperpolarization of TRN cell. A, TTX, In
TTX (1 µM), the group II agonist S3-C4HPG (500 µM) produces a membrane hyperpolarization.
A, MCPG + TTX, The S3-C4HPG
hyperpolarization is partially attenuated by the presence of the
general mGluR antagonist MCPG (500 µM). A,
Wash, After a 23 min wash in TTX-containing solution,
the S3-C4HPG-mediated hyperpolarization recovers. Initial Vm = 59 mV. B, Voltage-clamp recording in another TRN cell
showing that the mGluR-mediated effects are suppressed by
Cs+ in the electrode. B,
Control, In control conditions, ACPD produces a robust
alteration in baseline activity, presumably increasing spontaneous
EPSCs via suprathreshold activation of synaptically connected relay
neurons. B, TTX, In the presence of TTX
(1 µM), ACPD does not alter the holding current or
spontaneous baseline activity. C,
TTX, During voltage-clamp recording from a different TRN
neuron in TTX (1 µM), the selective group II mGluR
agonist S3-C4HPG produces no obvious change in resting current levels
or responses to voltage ramps.
|
|
| |
DISCUSSION |
Our results thus indicate that glutamate can produce postsynaptic
inhibitory responses in TRN cells in addition to the typical excitatory
action that has been described in many preparations. This inhibition
occurs through activation of group II mGluRs, which hyperpolarizes TRN
neurons by increasing a linear K+ conductance,
whereas activation of group I mGluRs suppresses a K+
conductance resulting in a membrane depolarization. Although the
predominant action of the general agonist ACPD is a depolarization, a
biphasic action of mGluR activation can occur within some TRN neurons,
suggesting the presence of both receptor subtypes on these cells.
Furthermore, although all TRN neurons tested produced the group I mGluR
mediated depolarization, approximately two-thirds also exhibited the
group II-mediated hyperpolarization. This difference suggests that
group II mGluRs are differentially distributed on TRN neurons or
perhaps that all TRN cells possess group II mGluR activity, but that
for some, the level of activity is insufficient to be detected by our
somatic recordings.
In any case, our findings indicate that activation of glutamatergic
inputs to many TRN cells from thalamocortical and/or
corticothalamic axons can provide both excitatory and
inhibitory influences depending on the specific glutamate
receptors activated. Of obvious importance is whether endogenous
activation of these different mGluR subtypes is specific to particular
glutamatergic afferents, such as a subset of corticothalamic and/or
thalamocortical axons. A precedent for such specificity exists in
thalamus for glutamatergic inputs. For example, activation of group I
mGluRs on relay neurons, which produces long-lasting EPSPs, appears
specific to the corticothalamic pathway and not the retinogeniculate,
both of which are glutamatergic (McCormick and von Krosigk, 1992;
Godwin et al., 1996).
Thus, the overall, sustained influence of activating these two mGluR
subtypes (groups I and/or II) by synaptically released glutamate on the
excitability of TRN neurons remains unknown. We assume that iGluRs
activated by these glutamatergic inputs provide relatively fast EPSPs,
and given evidence elsewhere that mGluR activation requires higher
afferent activity than does activation of iGluRs (McCormick and von
Krosigk, 1992), there could be an interesting frequency-dependent
effect in which certain corticothalamic or thalamocortical inputs to
TRN cells begin to inhibit these cells only when relatively active.
Also, the more sustained effects of mGluR activation would last well
beyond iGluR activation. We suggest three different possibilities that
require further investigation. First, individual glutamatergic
afferents can activate both group I and II mGluRs, leading to a
predominant excitatory response that negates small hyperpolarizing
actions. Second, individual glutamatergic afferents may activate only
group I or II mGluRs. If those activating group II mGluRs do not
activate iGluRs, the postsynaptic effect would be pure inhibition, and
even if they did activate both receptor types the mGluR-mediated
inhibition would outlast the iGluR-mediated excitation. Third, a given
axon may synapse on both group I and II mGluRs, but activation of these different subtypes may be differentially frequency-dependent, with one
effect dominating at lower levels of afferent activity, and the other,
at higher levels.
Although the functional significance of endogenous glutamate release on
mGluRs remains unanswered, our data suggest several hypotheses that
need further investigation. Clearly, TRN cells powerfully
inhibit thalamic relay cells, thereby providing an important control of
thalamic relay functions (Cox et al., 1997; Kim et al., 1997). As noted
above, all previous ideas of TRN functioning were based on the belief
that corticothalamic and thalamocortical axon collaterals, which form a
major input to TRN neurons, strictly excite these cells. The fact of
group II-mediated inhibition of TRN cells raises the possibility that
specific inputs from cortex or dorsal thalamus can inhibit TRN cells.
(In this sense, "specific" refers to certain afferents and/or
certain patterns of afferent activity.) Our data thus indicate that
significant inhibition may also result from corticothalamic and/or
thalamocortical inputs to TRN cells. If so, then ideas of TRN
functioning and control by these glutamatergic afferents are more
complex and richer than previously thought.
| |
FOOTNOTES |
Received March 15, 1999; revised May 15, 1999; accepted May 20, 1999.
This research was supported by National Eye Institute Grant EY03038
from the National Institutes of Health.
Correspondence should be addressed to S. M. Sherman, Department of
Neurobiology, State University of New York, Stony Brook, NY 11794-5230.
| |
REFERENCES |
-
Avoli M,
Gloor P,
Kostopoulos G
(1990)
Thalamocortical relationships in generalized epilepsy with bilaterally synchronous spike-and-wave discharge.
In: Generalized epilepsy: neurobiological approaches (Avoli M,
Gloor P,
Kostopoulos G,
Naquet R,
eds), pp 190-212. Boston: Birkhauser.
-
Buzsáki G,
Smith A,
Berger S,
Fisher LJ,
Gage FH
(1990)
Petit mal epilepsy and parkinsonian tremor: hypothesis of a common pacemaker.
Neuroscience
36:1-14[ISI][Medline].
-
Charpak S,
Gähwiler BH,
Do K-Q,
Knöpfel T
(1990)
Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters.
Nature
347:765-767[Medline].
-
Collingridge GL,
Lester RA
(1989)
Excitatory amino acid receptors in the vertebrate central nervous system.
Pharmacol Rev
40:143-210.
-
Conn PJ,
Pin JP
(1997)
Pharmacology and functions of metabotropic glutamate receptors.
Annu Rev Pharmacol Toxicol
37:205-237[ISI][Medline].
-
Cox CL,
Huguenard JR,
Prince DA
(1995)
Cholecystokinin depolarizes rat thalamic reticular neurons by suppressing a K+ conductance.
J Neurophysiol
74:990-1000[Abstract/Free Full Text].
-
Cox CL,
Huguenard JR,
Prince DA
(1997)
Nucleus reticularis neurons mediate diverse inhibitory effects in thalamus.
Proc Natl Acad Sci USA
94:8854-8859[Abstract/Free Full Text].
-
Cox CL,
Zhou Q,
Sherman SM
(1998)
Glutamate locally activates dendritic outputs of thalamic interneurons.
Nature
394:478-482[Medline].
-
Davies CH,
Clarke VR,
Jane DE,
Collingridge GL
(1995)
Pharmacology of postsynaptic metabotropic glutamate receptors in rat hippocampal CA1 pyramidal neurones.
Br J Pharmacol
116:1859-1869[ISI][Medline].
-
Eaton SA,
Salt TE
(1996)
Role of N-methyl-D-aspartate and metabotropic glutamate receptors in corticothalamic excitatory postsynaptic potentials in vivo.
Neuroscience
73:1-5[ISI][Medline].
-
Fiorillo CD,
Williams JT
(1998)
Glutamate mediates an inhibitory postsynaptic potential in dopamine neurons.
Nature
394:78-82[Medline].
-
Godwin DW,
Van Horn SC,
Erisir A,
Sesma M,
Romano C,
Sherman SM
(1996)
Ultrastructural localization suggests that retinal and cortical inputs access different metabotropic glutamate receptors in the lateral geniculate nucleus.
J Neurosci
16:8181-8192[Abstract/Free Full Text].
-
Holmes KH,
Keele NB,
Arvanov VL,
Shinnick-Gallagher P
(1996)
Metabotropic glutamate receptor agonist-induced hyperpolarizations in rat basolateral amygdala neurons: receptor characterization and ion channels.
J Neurophysiol
76:3059-3069[Abstract/Free Full Text].
-
Jones EG
(1985)
In: The thalamus. New York: Plenum.
-
Kim U,
Sanchez-Vives MV,
McCormick DA
(1997)
Functional dynamics of GABAergic inhibition in the thalamus.
Science
278:130-134[Abstract/Free Full Text].
-
Lee KH,
McCormick DA
(1997)
Modulation of spindle oscillations by acetylcholine, cholecystokinin and 1S,3R-ACPD in the ferret lateral geniculate and perigeniculate nuclei in vitro.
Neuroscience
77:335-350[ISI][Medline].
-
Lee SM,
Friedberg MH,
Ebner FF
(1994a)
The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. I. Assessment of receptive field changes following thalamic reticular nucleus lesions.
J Neurophysiol
71:1702-1715[Abstract/Free Full Text].
-
Lee SM,
Friedberg MH,
Ebner FF
(1994b)
The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. II. Differential effects of GABAA and GABAB receptor antagonists on responses of VPM neurons.
J Neurophysiol
71:1716-1726[Abstract/Free Full Text].
-
McCormick DA,
von Krosigk M
(1992)
Corticothalamic activation modulates thalamic firing through glutamate "metabotropic" receptors.
Proc Natl Acad Sci USA
89:2774-2778[Abstract/Free Full Text].
-
Mercuri NB,
Stratta F,
Calabresi P,
Bonci A,
Bernardi G
(1993)
Activation of metabotropic glutamate receptors induces an inward current in rat dopamine mesencephalic neurons.
Neuroscience
56:399-407[ISI][Medline].
-
Nakanishi S
(1992)
Molecular diversity of glutamate receptors and implications for brain function.
Science
258:597-603[Abstract/Free Full Text].
-
Ohishi H,
Shigemoto R,
Nakanishi S,
Mizuno N
(1993a)
Distribution of the messenger RNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat.
Neuroscience
53:1009-1018[ISI][Medline].
-
Ohishi H,
Shigemoto R,
Nakanishi S,
Mizuno N
(1993b)
Distribution of the mRNA for a metabotropic glutamate receptor (mGluR3) in the rat brain: an in situ hybridization study.
J Comp Neurol
335:252-266[ISI][Medline].
-
Sanchez-Vives MV,
Bal T,
McCormick DA
(1997)
Inhibitory interactions between perigeniculate GABAergic neurons.
J Neurosci
17:8894-8908[Abstract/Free Full Text].
-
Schoepp DD,
Conn PJ
(1993)
Metabotropic glutamate receptors in brain function and pathology.
Trends Neurosci
14:13-20.
-
Shirasaki T,
Harata N,
Akaike A
(1994)
Metabotropic glutamate response in acutely dissociated hippocampal CA1 pyramidal neurones of the rat.
J Physiol (Lond)
475:439-453[Abstract/Free Full Text].
-
Steriade M,
Domich L,
Oakson G
(1986)
Reticularis thalami neurons revisited: activity changes during shifts in states of vigilance.
J Neurosci
6:68-81[Abstract].
-
Steriade M,
McCormick DA,
Sejnowski TJ
(1993)
Thalamocortical oscillations in the sleeping and aroused brain.
Science
262:679-685[Abstract/Free Full Text].
-
Turner JP,
Salt TE
(1998)
Characterization of sensory and corticothalamic excitatory inputs to rat thalamocortical neurones in vitro.
J Physiol (Lond)
510:829-843[Abstract/Free Full Text].
-
Watkins JC,
Evans RH
(1981)
Excitatory amino acid transmitters.
Annu Rev Pharmacol Toxicol
21:165-204[ISI][Medline].
Copyright © 1999 Society for Neuroscience 0270-6474/99/19156694-06$05.00/0
This article has been cited by other articles:
|
|
|
|
 
N. Cotillon-Williams, C. Huetz, E. Hennevin, and J.-M. Edeline
Tonotopic Control of Auditory Thalamus Frequency Tuning by Reticular Thalamic Neurons
J Neurophysiol,
March 1, 2008;
99(3):
1137 - 1151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Govindaiah and C. L. Cox
Metabotropic Glutamate Receptors Differentially Regulate GABAergic Inhibition in Thalamus
J. Neurosci.,
December 27, 2006;
26(52):
13443 - 13453.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-H. Lee and C. L. Cox
Excitatory Actions of Vasoactive Intestinal Peptide on Mouse Thalamocortical Neurons Are Mediated by VPAC2 Receptors
J Neurophysiol,
August 1, 2006;
96(2):
858 - 871.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. Blethyn, S. W. Hughes, T. I. Toth, D. W. Cope, and V. Crunelli
Neuronal Basis of the Slow (<1 Hz) Oscillation in Neurons of the Nucleus Reticularis Thalami In Vitro
J. Neurosci.,
March 1, 2006;
26(9):
2474 - 2486.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Long, C. E. Landisman, and B. W. Connors
Small Clusters of Electrically Coupled Neurons Generate Synchronous Rhythms in the Thalamic Reticular Nucleus
J. Neurosci.,
January 14, 2004;
24(2):
341 - 349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Cox, I. Reichova, and S. M. Sherman
Functional Synaptic Contacts by Intranuclear Axon Collaterals of Thalamic Relay Neurons
J. Neurosci.,
August 20, 2003;
23(20):
7642 - 7646.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Slaght, N. Leresche, J.-M. Deniau, V. Crunelli, and S. Charpier
Activity of Thalamic Reticular Neurons during Spontaneous Genetically Determined Spike and Wave Discharges
J. Neurosci.,
March 15, 2002;
22(6):
2323 - 2334.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. D. Schoepp
Unveiling the Functions of Presynaptic Metabotropic Glutamate Receptors in the Central Nervous System
J. Pharmacol. Exp. Ther.,
October 1, 2001;
299(1):
12 - 20.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Hillenbrand and J. L. van Hemmen
Does Corticothalamic Feedback Control Cortical Velocity Tuning?
Neural Comput.,
February 1, 2001;
13(2):
327 - 355.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. J. Ramcharan, C. L. Cox, X. J. Zhan, S. M. Sherman, and J. W. Gnadt
Cellular Mechanisms Underlying Activity Patterns in the Monkey Thalamus During Visual Behavior
J Neurophysiol,
October 1, 2000;
84(4):
1982 - 1987.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Bal, D. Debay, and A. Destexhe
Cortical Feedback Controls the Frequency and Synchrony of Oscillations in the Visual Thalamus
J. Neurosci.,
October 1, 2000;
20(19):
7478 - 7488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. J. Zhan, C. L. Cox, and S. M. Sherman
Dendritic Depolarization Efficiently Attenuates Low-Threshold Calcium Spikes in Thalamic Relay Cells
J. Neurosci.,
May 15, 2000;
20(10):
3909 - 3914.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. D. Weese, J. M. Phillips, and V. J. Brown
Attentional Orienting Is Impaired by Unilateral Lesions of the Thalamic Reticular Nucleus in the Rat
J. Neurosci.,
November 15, 1999;
19(22):
10135 - 10139.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
.gif?ad=17923&adview=true)
TOP
ABSTRACT
INTRODUCTION
