Download Pontine Gustatory Activity Is Altered by Electrical Stimulation in the

Pontine Gustatory Activity Is Altered by Electrical Stimulation in the
Central Nucleus of the Amygdala
ROBERT F. LUNDY JR. AND RALPH NORGREN
Department of Behavioral Science, Penn State College of Medicine, Hershey, Pennsylvania 17033
Received 15 July 2000; accepted in final form 30 October 2000
Visceral signals and experience modulate the acceptance of
gustatory stimuli and, consequently, the consumption of foodstuff. For instance, the association of taste with gastrointestinal
malaise (conditioned taste aversion) can prevent the subsequent ingestion of the tastant (Garcia et al. 1955; Grill 1985;
Nachman and Ashe 1973), while dietary sodium deficiency can
produce an avid consumption of previously avoided concentrations of NaCl (Berridge et al. 1984; Contreras and Hatton
1975; Nachman 1962; Richter 1936). The pontine parabrachial
nucleus (PBN) appears to be a critical neural substrate for these
taste-guided behaviors because bilateral lesions of this area
severely disrupt their expression (Grigson et al. 1993; Scalera
et al. 1995; Spector et al. 1992). In normal animals, both
conditioned taste aversion and sodium appetite selectively alter
gustatory evoked responses in the brain stem (Chang and Scott
1984; Nakamura and Norgren 1995; Shimura et al. 1997;
Tamura and Norgren 1997; Yasoshima et al. 1995). One interpretation of this modulation in response to visceral signals
and experience is that centrifugal activity normally regulates
gustatory processing in the brain stem. This is supported by the
fact that chronically decerebrate rats fail to acquire a learned
taste aversion or to express a salt appetite (Grill et al. 1986).
The PBN distributes gustatory information to the hypothalamus, amygdala, bed nucleus of the stria terminalis, and, via
the thalamus, to insular cortex and, in turn, receives projections
from these brain structures (Halsell 1992; Hopkins and Holstege 1978; Norgren 1976; Roberts 1980; Saper and Loewy
1980; Veening et al. 1984). These forebrain regions participate
in autonomic and endocrine functions, and each has been
implicated in the expression of complex taste-guided behaviors
(Bermudez-Rattoni and McGaugh 1991; Johnson et al. 1999;
Loewy and Spyer 1990; Roth et al. 1973; Ruger and Schulkin
1980; Zardetto-Smith et al. 1994). The influence of descending
input from these rostral structures on the neurophysiology of
brain stem gustatory neurons has received little attention. Prior
studies have shown that electrical stimulation in the lateral
hypothalamus (Bereiter et al. 1980; Matsuo and Kusano 1984;
Matsuo et al. 1984; Murzi et al. 1986) modulated gustatoryresponsive neurons in the rostral nucleus of the solitary tract,
but not in the PBN (Murzi et al. 1986). Activity in gustatory
cortex, on the other hand, altered the ongoing spontaneous
discharge of both nucleus of the solitary tract (NST) and PBN
gustatory neurons (DiLorenzo and Monroe 1992; Smith and Li
2000). None of these studies tested for alterations in gustatory
evoked activity.
The choice to stimulate in the central nucleus of the amygdala (CeA) was based on the fact that it is a major recipient of
PBN gustatory afferent axons, as well as the major source of
Address for reprint requests: R. F. Lundy Jr., Dept. of Behavioral Science,
Penn State College of Medicine, 500 University Dr., Hershey, PA 17033
(E-mail: [email protected]).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked ‘‘advertisement’’
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
INTRODUCTION
770
0022-3077/01 $5.00 Copyright © 2001 The American Physiological Society
www.jn.physiology.org
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
Lundy, Robert F., Jr. and Ralph Norgren. Pontine gustatory activity is altered by electrical stimulation in the central nucleus of the
amygdala. J Neurophysiol 85: 770 –783, 2001. Visceral signals and
experience modulate the responses of brain stem neurons to gustatory
stimuli. Both behavioral and anatomical evidence suggests that this
modulation may involve descending input from the forebrain. The
present study investigates the centrifugal control of gustatory neural
activity in the parabrachial nucleus (PBN). Extracellular responses
were recorded from 51 single PBN neurons during application of
sucrose, NaCl, NaCl mixed with amiloride, citric acid, and QHCl with
or without concurrent electrical stimulation in the ipsilateral central
nucleus of the amygdala (CeA). Based on the sapid stimulus that
evoked the greatest discharge, 3 neurons were classified as sucrosebest, 32 as NaCl-best, and 16 as citric acid-best. In most of the
neurons sampled, response rates to an effective stimulus were either
inhibited or unchanged during electrical stimulation of the CeA.
Stimulation in the CeA was without effect in two sucrose-best neurons, nine NaCl-best neurons, and one citric acid-best neuron. Suppression was evident in 1 sucrose-best neuron, 18 NaCl-best neurons,
and 15 citric acid-best neurons. In NaCl-best neurons inhibited by
CeA stimulation, the magnitude of the effect was similar for spontaneous activity and responses to the five taste stimuli. Nonetheless, the
inhibitory modulation of gustatory sensitivity increased the relative
effectiveness of NaCl resulting in narrower chemical selectivity. For
citric acid– best neurons, the magnitude of inhibition produced by
CeA activation increased with an increase in stimulus effectiveness.
The responses to citric acid were inhibited significantly more than the
responses to all other stimuli with the exception of NaCl mixed with
amiloride. The overall effect was to change these CA-best neurons to
CA/NaCl-best neurons. In a smaller subset of NaCl-best neurons (n ⫽
5), CeA stimulation augmented the responsiveness to NaCl but was
without effect on the other stimuli or on baseline activity. It appears
that electrical stimulation in the CeA modulates response intensity, as
well as the type of gustatory information that is transmitted in a subset
of NaCl-best neurons. These findings provide an additional link between the amygdala and the PBN in the control of NaCl intake,
modulating the response and the chemical selectivity of an amiloridesensitive Na⫹-detecting input pathway.
FOREBRAIN STIMULATION AND GUSTATORY PROCESSING
METHODS
Subjects
Neurophysiological recordings were made in 25 male SpragueDawley rats weighing 360 –500 g [CrL:CD (SD) BR; Charles River
Breeding Laboratories]. The animals were maintained in a temperature-controlled colony room on a 12-h light/dark cycle and allowed
free access to normal rat chow (Teklad 8604) and distilled water.
Amygdala stimulating electrodes
The rats were anesthetized with a 50-mg/kg injection (ip) of pentobarbital sodium (Nembutal). Additional doses of Nembutal (0.1 ml)
were administered as necessary to continue a deep level of anesthesia.
Rectal temperature was monitored throughout a recording session and
maintained at 37 ⫾ 0.2°C. The trachea was cannulated with polyethylene 210 tubing, and a small suture was attached to the ventral
surface of the tongue. Animals were then secured in a stereotaxic
instrument using nonpuncture ear bars (45° taper) and a bite bar. A
midline incision was made and the skull leveled between ␤ and ␭.
Three 140-␮m-diam stainless steel electrodes, insulated except at the
cross section of the tip, were lowered into the central nucleus of the
amygdala (CeA) using the following stereotaxic coordinates relative
to ␤: P ⫺1.8 mm, L 4.0 mm, and V 8.5 mm. A small hole was drilled
through the skull at the P-L coordinates, and the dura was excised.
The stimulating electrodes were lowered through the cortical tissue
using a custom-made jig that spaced the electrodes 0.5 mm apart and
oriented them in the AP plane. The electrodes were anchored with
dental cement via a stainless steel screw in the skull just posterior to
the electrodes. Electrical stimulation in the amygdala was achieved
using a Grass S 48 train generator attached to a constant current
source (PSIU6), which, in turn, was connected to a switch box that
could distribute the current to any possible pair of the 3 electrodes.
Stimulation parameters were 1-s trains of 10 pulses delivered at 0.5
Hz for 10 s (total of 5 trains). The duration and amplitude of an
individual pulse were 0.2 ms and 0.4 mA, respectively.
Localization of PBN gustatory neurons
After drilling a small hole through the interparietal bone, glassinsulated tungsten electrodes (resistance 2– 8 M⍀) were lowered into
the PBN using a Fredrick Haer micropositioner. To avoid the transverse sinus, the electrode was oriented 20° off the vertical with the tip
pointed rostrally. A drop in background activity marked the boundary
between the cerebellum and the pons, and, at that point, any neuron
encountered was tested for its sensitivity to 0.1 M NaCl applied to the
anterior two-thirds of the tongue. If a response was not obtained with
NaCl, then 0.3 M sucrose, 0.01 M citric acid, and 0.003 M quinine
hydrochloride were tested. Neural activity was amplified (⫻1,000),
fed through an artifact suppresser, monitored with an oscilloscope and
audiomonitor, and stored on a audio-cassette recorder for off-line
analysis. The artifact suppresser was used to adjust the size of the
electrical stimulation artifact to be easily distinguished from the
neural signal during off-line analysis. Cambridge Electronic Design’s
Spike2 hardware and software were used to convert the recorded data
to digital format.
The neural signal and the artifact signal were individually classified
and separated into two wavemark channels using Spike2 hardware
and software. The channel with the artifact signal was used to mark
the onset and offset of the electrical pulses. This procedure removes
the background noise from the recording (see Fig. 5) and functions as
a window discriminator in conjunction with waveform matching. The
analog signal is digitized at 20,000 Hz and templates formed during an
initial sampling period (60 s). Subsequently, the matching algorithm is
engaged only if the digitized voltage levels reach a prespecified value.
Spikes are then included in a template only if more than a user-defined
percentage of the points in a spike fall within the template. The
present study characterized a spike with 75 points. It then required that
⬎60% of the points match, and that the difference in amplitude
between template and spike be ⬍20% for any potential to be counted.
In two instances, Spike2 was used to separate the activity of two
different action potentials recorded from the same site.
Stimulus delivery and protocols
The tongue was gently extended out from the oral cavity using the
ventral tongue suture. A computer-controlled delivery system was
used for taste stimulus and water presentation to the anterior tongue.
For 10 s before and for longer after stimulus offset, a separate outflow
nozzle delivered deionized-distilled water to the same locus on the
tongue. During the rinse period, the stimulus delivery line and nozzle
were flushed with water. Gustatory neurons were tested for responsiveness to 0.3 M sucrose, 0.1 M NaCl, 0.1 M NaCl mixed with 10
␮M amiloride, 0.01 M citric acid (CA), and 0.003 M quinine hydrochloride (QHCl) using a water, stimulus, water procedure. Stimulus
order varied from one recording session to another. Briefly, water was
applied to the tongue for 10 s followed by tastant application for 10 s.
The water flow that followed tastant application was for 90 s, and the
total time between different stimulus applications was 2 min. The
stimulation protocol was as follows: control series 1–test series–
control series 2. Tastant application during a control series was
without CeA stimulation. Prior to the test series, baseline activity in
the absence of fluid flowing over the tongue was recorded during CeA
stimulation. After another 2–3 min, the test series began and the
tastants were applied during concurrent CeA stimulation. In most
cases a neuron was held long enough to complete the second control
series. This was done to assess the stability of the recorded neuron and
to determine whether CeA stimulation produced any prolonged effects
on gustatory responsiveness.
Data analysis
Corrected neural responses to a taste stimulus were calculated by
subtracting the 10-s discharge rate to each stimulus from its preceding
10-s discharge rate to water. The 10-s response measure was used to
categorize individual neurons based on the stimulus that evoked the
greatest discharge. When a neuron was tested with both control series
1 and 2, these response rates were averaged. During the test series,
seconds 1, 3, 5, 7, and 9 of tastant application correspond to the time
periods when pulse trains were delivered to the CeA, while seconds 2,
4, 6, 8, and 10 correspond to the time periods between pulse trains.
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
amygdaloid efferents to the brain stem (Halsell 1992; Norgren
1976; Veening et al. 1984). In addition, neurophysiological
studies examining cardiovascular and respiratory sensitive neurons in the amygdala and PBN showed that neurons recorded
in one area were influenced by electrical stimulation in the
other (Cechetto and Calaresu 1983; Jhamandas et al. 1996).
The effect of such forebrain stimulation on the responses of
gustatory neurons in the PBN has not been examined.
The present study characterizes the influence of the CeA on
gustatory processing at the level of the PBN. We recorded
responses of single PBN neurons to gustatory stimuli applied
before, during, and after concurrent electrical stimulation in the
CeA. Amygdala stimulation was found to modulate both ongoing spontaneous discharge and tastant-evoked responses in
PBN gustatory neurons. These alterations in gustatory sensitivity mimic those produced by the induction of a sodium
appetite.
A portion of this work was presented as a poster at the 2000
meeting of the Association for Chemoreception Sciences.
771
772
R. F. LUNDY AND R. NORGREN
Neurons in the present study were classified as inhibited or augmented
if these response measures differed from their corresponding control
rates by ⬍25 or ⬎25%, respectively. A difference score was calculated by subtracting the test series response rates from the control
series response rates during seconds 1, 3, 5, 7, and 9 and 2, 4, 6, 8, and
10. The breadth of responsiveness was calculated according to the
formula H ⫽ ⫺K ⌺ pI log pI, where K is a scaling constant (1.66 for
4 stimuli; sucrose, NaCl, CA, QHCl) and pI is the proportion of the
response to each of the stimuli against the total response to all the
stimuli (Smith and Travers 1979).
One- and two-way ANOVAs were performed to detect significant
differences between response rates. In some instances, post hoc contrast analyses (least significant difference) were used to determine the
source of statistically significant differences. One-sample t-tests were
FIG. 2. A photomicrograph of a coronal section through the
amygdala (cresyl violet stain). The track left by a stimulating
electrode ends in the central nucleus of the amygdala (dashed
line). Three additional amygdaloid nuclei are shown (dotted
lines). MA, medial nucleus; BLA, basolateral nucleus; LA, lateral
nucleus.
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
FIG. 1. Top left: photomicrograph of a coronal section through the parabrachial nucleus (PBN) where taste responsive neurons
were isolated (cresyl violet stain). The black arrow points to a marking lesion made following the recording of a gustatory neuron;
3 electrode tracks are also visible. The approximate area in which taste-responsive neurons were isolated at various PBN levels is
illustrated by a filled oval in the 3 line drawings. LC, locus coeruleus; LBP, lateral parabrachial nucleus; LSO, lateral superior olive;
Me5, mesencephalic trigeminal nucleus; MPB, medial parabrachial nucleus; Mo5, trigeminal motor nucleus; Pr5DM, dorsomedial
aspect of the principal sensory trigeminal nucleus; Pr5VL, ventrolateral aspect of the principal sensory trigeminal nucleus (redrawn
from Paxinos and Watson 1986).
FOREBRAIN STIMULATION AND GUSTATORY PROCESSING
773
used to determine whether the absolute difference scores differed
from 0. A change in stimulus-evoked activity was considered significant when it differed above or below the response rate to water flow
by ⱖ2.5 standard deviations. The results will be shown as the mean ⫾
SE. Data analyses were done using SPSS, and P values ⬍0.05 were
considered significant.
Histological processing and analyses
At the end of an experiment, a small electrolytic lesion (5 ␮A for
30 s) was made at the site of the last recorded gustatory neuron. The
rats were given a lethal dose of Nembutal (100 mg/kg ip) and perfused
intracardially with 0.9% saline followed by 10% Formalin. The brain
was removed, cut coronally in 50-␮m sections using a freezing
microtome, and stained with the cresyl Lecht violet. The lesion mark
and stimulating electrode tracks were detected using a light-field
microscope and the loci noted.
medial quadrant of the PBN. Figure 1 shows a photomicrograph of a coronal section through the PBN and line drawings
that correspond to three different levels of the PBN. The black
arrow indicates the marking lesion made following the recording of a gustatory neuron; three electrode tracks are visible.
The approximate area in which taste-responsive neurons were
isolated at various PBN levels is illustrated by a filled oval in
the line drawings (Paxinos and Watson 1986). The present
taste-responsive zone matched closely the area reported in
previous studies (Nishijo and Norgren 1990; Norgren and
Pfaffmann 1975; Scott and Perrotto 1980). The photomicrograph in Fig. 2 shows the track of a stimulating electrode
placed in the CeA. Neurophysiological data in the present
study were obtained from animals in which the stimulating
electrodes were histologically confirmed to terminate in the
CeA.
RESULTS
Histology
Neuronal categorization
Based on stereotaxic coordinates of the penetrations and the
marking lesions, gustatory neurons were isolated in the caudo-
Fifty-one gustatory neurons were isolated in the PBN and
tested with the five taste stimuli with and without concurrent
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
FIG. 3. The response profiles of the 51 gustatory
neurons recorded in the PBN. Neurons were
grouped based on the stimulus that evoked the greatest discharge with sucrose-best neurons on the left,
NaCl-best in the middle, and citric acid-best on the
right. The taste stimuli tested and the spontaneous
activity during the 10-s prestimulus water flow are
arranged from top to bottom. Within a neural category, response rates to the best stimulus are arranged in descending order. Filled bars in the taste
stimulus plots represent response rates that were
significantly different from those during prestimulus
water flow.
774
R. F. LUNDY AND R. NORGREN
Amygdala stimulation
Figure 5 shows the response of a CA-best neuron to sucrose,
NaCl, CA, and QHCl with and without concurrent CeA stimulation. The labels to the left of each raw record indicates the
stimulus; the labels with the acronym CeA indicate stimulus
applications during amygdala activation. With regard to the
bottom record, the effect of CeA stimulation was assessed on
the baseline activity when no fluid flowed over the tongue
(Baseline/CeA). The first and third long black bar in each taste
stimulus record corresponds to 10 s of water flow, and the
second (middle) black bar is stimulus application. The short
black bars in the records with the CeA acronym indicate the
five 1-s pulse trains delivered to the CeA. The first three
records show the responses to sucrose with and without concurrent CeA stimulation. To appreciate the typical signal-tonoise ratio obtained in the present study, the first two records
are shown with the background noise included. Raw record 3
differs from record 2 only in that Spike2 was used to remove
the background noise and extract the CeA stimulation artifacts
(e.g., shorter vertical lines above pulse train marks in record 2),
the spike data were unmodified. This figure shows that electrical pulses delivered to the CeA produced a significant reduction in the baseline and tastant-evoked discharge rates.
NaCl-best neurons
Of the 32 NaCl-best neurons, electrical pulse trains delivered to the CeA inhibited gustatory responses in 18, augmented
responses in 5, and were ineffective in 9. Only the results for
neurons inhibited (amiloride sensitive and insensitive) and
augmented (amiloride sensitive) will be shown. For the neurons that were inhibited, Fig. 6A shows the responses to the five
stimuli applied before and after the applications during amygdala stimulation. The discharge rates were nearly identical,
indicating that the recording was stable and CeA activation was
without a prolonged influence on gustatory responsiveness
(F1,160 ⫽ 0.0, P ⫽ 0.99). During delivery of the pulse trains to
the CeA, the response rate to each stimulus was suppressed
(Fig. 6B, F1,176 ⫽ 10.9, P ⬍ 0.01). In contrast, the response
rates to the taste stimuli between the pulse trains (seconds 2, 4,
6, 8, and 10) were comparable to the response rates during the
same time periods in the control series (Fig. 6C, F1,176 ⫽ 0.2,
P ⫽ 0.63). This indicates that the effect of CeA activation
rapidly reversed. The difference in response rates to the taste
stimuli and the effect of the pulse trains on baseline activity
during the same time periods are shown in Fig. 6D. One-
FIG. 4. Shown are the mean corrected response rates to each stimulus in neurons categorized as sucrose-best, NaCl-best, NaClgeneralists, and citric acid– best. The number
of neurons in each group is shown in parentheses.
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
electrical stimulation in the CeA. The response profiles of these
neurons are shown in Fig. 3. The taste stimuli tested and the
activity of each neuron during the 10-s prestimulus water flow
are arranged from top to bottom and the different neuron
groups from left to right. Within each group, neurons are
arranged by their response rate to the best stimulus in descending order. Neurons 1–3 were deemed sucrose-best, neurons
4 –35 NaCl-best, and neurons 36 –51 CA-best. Although neurons 31–35 were NaCl-best, they differed from the other NaClbest neurons insofar as their response to NaCl was insensitive
to amiloride. They were termed NaCl generalists (Lundy and
Contreras 1999).
The mean corrected response rates to each stimulus as a
function of neuron type is shown in Fig. 4. Separate one-way
ANOVA tests revealed a significant main effect for stimulus in
NaCl-best (F4,135 ⫽ 42.3, P ⬍ 0.01) and CA-best neurons
(F4,76 ⫽ 19.8, P ⬍ 0.01). Post hoc analyses indicated that the
order of stimulus effectiveness for NaCl-best neurons was
NaCl ⬎ NaCl ⫹ amiloride ⫽ CA ⫽ sucrose ⬎ QHCl. In the
case of CA-best neurons, the order was CA ⬎ NaCl ⫽ NaCl ⫹
amiloride ⬎ sucrose ⫽ QHCl. Figure 4 also shows clearly that
the epithelial Na⫹ channel antagonist amiloride was only effective in suppressing response rates to NaCl in NaCl-best
neurons. In subsequent analyses, the 2 NaCl-best groups were
combined because no clear differences were observed in terms
of the effects of CeA stimulation on neural responsiveness.
FOREBRAIN STIMULATION AND GUSTATORY PROCESSING
775
sample t-tests revealed that the baseline activity and the discharge rate to each stimulus differed significantly from 0 only
during the pulse trains (P values ⱕ0.01). Although, the degree
of inhibition was comparable for spontaneous activity and
taste-evoked responses (F5,105 ⫽ 1.7, P ⫽ 0.12), CeA stimulation reduced the number of neurons that responded significantly to sucrose from 10 to 5, to NaCl/Amiloride from 16 to
14, to CA from 13 to 8, and to QHCl from 11 to 2.
In another subset of NaCl-best neurons, CeA activation
increased the responsiveness to NaCl. The stimulus-evoked
responses in this group were stable between the two control
series applications (Fig. 7A, F1,40 ⫽ 0.02, P ⫽ 0.87). Although
the response rate of all five neurons to NaCl increased (range,
26 –95%) during the pulse trains, the effect was not statistically
significant (Fig. 7B, F1,50 ⫽ 1.1, P ⫽ 0.3). Analysis of the
difference scores in Fig. 7D, however, showed that the increase
in response rate to NaCl differed significantly from 0 during
both concurrent CeA stimulation (t-test, P ⬍ 0.01) and between pulse trains (t-test, P ⫽ 0.01). A two-way ANOVA on
the difference scores revealed a significant interaction between
stimulus and measurement period (F5,60 ⫽ 6.1, P ⬍ 0.01). Post
hoc analyses indicated that the increase in NaCl responsiveness
between pulse trains was less than that during the pulse trains
(P ⬍ 0.01). Interestingly, this amygdala-induced facilitation of
NaCl-evoked responses was disrupted by amiloride and occurred in the absence of an effect on baseline activity. The
number of neurons responsive to sucrose was reduced from
three to two, to CA from four to two, and to QHCl from one to
zero.
CA-best neurons
With the exception of one unaffected neuron, the influence
of amygdala stimulation on CA-best neurons was always inhibitory. Before and after CeA stimulation, the evoked responses were stable (F1,160 ⫽ 0.1, P ⫽ 0.72; Fig. 8A). Electrical pulses delivered to the CeA dramatically suppressed the
discharge rate of PBN cells to each taste stimulus (Fig. 8B,
F1,142 ⫽ 22.3, P ⬍ 0.01). In fact, a post hoc analysis on the
stimulus main effect during CeA stimulation (F4,70 ⫽ 14.8,
P ⬍ 0.01) indicated that the response rates to NaCl and CA
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
FIG. 5. The responses of a CA-best neuron to sucrose, NaCl, CA, and QHCl with and without concurrent CeA stimulation. See text for details.
776
R. F. LUNDY AND R. NORGREN
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
FIG. 6. Data from the NaCl-best neurons that were inhibited by CeA stimulation. A: the responses to the 5 stimuli applied before
(䊐) and after (s) the trials with concurrent amygdala stimulation. B: the response rates during stimulation of the CeA (■) and during
the corresponding periods in trials without CeA stimulation (䊐). C: the response rates during the time periods between CeA pulse
trains (p) and during the corresponding periods without CeA stimulation (䊐). D: the difference between the response rates shown
in panels B (■) and C (o). The effect of the pulse trains on baseline activity during the same time periods is also shown in D
(Baseline). F, test series significantly different from control series; †, significantly different from 0.
were no longer significantly different (P ⫽ 0.26). During the
time periods between pulse trains, the response rates tended to
recover to control levels (Fig. 8C, F1,142 ⫽ 2.7, P ⫽ 0.09).
One-sample t-tests indicated that the baseline activity and
discharge rates to each tastant were significantly different from
0 during the pulse trains (Fig. 8D, P values ⬍0.01). The degree
of inhibition varied with stimulus effectiveness (F5,85 ⫽ 4.6,
P ⬍ 0.01); responses to CA were inhibited significantly more
FOREBRAIN STIMULATION AND GUSTATORY PROCESSING
777
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
FIG. 7. Data from the NaCl-best neurons that were facilitated by CeA stimulation. A: the responses to the 5 stimuli applied
before (䊐) and after (s) the trials with concurrent amygdala stimulation. B: the response rates during stimulation of the CeA (■)
and during the corresponding periods in trials without CeA stimulation (䊐). C: the response rates during the time periods between
CeA pulse trains (o) and during the corresponding periods without CeA stimulation (䊐). D: the difference between the response
rates shown in B (■) and C (o). The effect of the pulse trains on baseline activity during the same time periods is also shown in
D (Baseline). ‡, significantly different from 0 and baseline activity.
than the responses to all other stimuli (P values ⱕ0.03) with
the exception of NaCl mixed with amiloride (P ⫽ 0.08).
Responses to NaCl, NaCl/Amiloride, and CA, but not to sucrose and QHCl, were inhibited to a greater degree than was
the baseline activity. Between pulse trains, the inhibitory effect
did not fully reverse when NaCl or CA was the stimulus (t-test,
P values ⱕ0.02). The residual inhibition of CA responses was
significantly different from sucrose, NaCl/Amiloride, QHCl,
778
R. F. LUNDY AND R. NORGREN
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
FIG. 8. Data from the citric acid– best neurons that were inhibited by CeA stimulation. A: the responses to the 5 stimuli applied
before (䊐) and after (s) the trials with concurrent amygdala stimulation. B: the response rates during stimulation of the CeA (■)
and during the corresponding periods in trials without CeA stimulation (䊐). C: the response rates during the time periods between
CeA pulse trains (o) and during the corresponding periods without CeA stimulation (䊐). D: the difference between the response
rates shown in B (■) and in C (o). The effect of the pulse trains on baseline activity during the same time periods is also shown
in D (Baseline). F, test series significantly different from control series; †, significantly different from 0; ‡, significantly different
from 0 and baseline activity.
and baseline activity (P values ⱕ0.01). As with NaCl-best
neurons, the percentage of CA-best neurons that responded to
stimuli other than their best stimulus was reduced during CeA
stimulation. The number of neurons responding to sucrose
decreased from 10 to 3, to NaCl and NaCl/Amiloride from 15
to 14, and to QHCl from 10 to 5.
FOREBRAIN STIMULATION AND GUSTATORY PROCESSING
779
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
FIG. 9. The entropy measure for the NaCl-best and the CA-best neurons that were inhibited and the NaCl-best neurons that were
facilitated by CeA stimulation (A). This metric of stimulus responsiveness was calculated using the neural responses to 0.3 M
sucrose, 0.1 M NaCl, 0.01 M CA, and 0.003 M QHCl. A value of 0 indicates that neurons were responsive to only one of the four
stimuli, while a value of 1 indicates that they were equally responsive to the 4 stimuli. In this and subsequent plots, the open bars
represent values without concurrent CeA stimulation, and the dark bars represent values during concurrent CeA stimulation. B: the
percentage overall evoked activity elicited by each stimulus in the NaCl-best neurons under inhibitory control by CeA stimulation.
C: the NaCl-best neurons under excitatory control. D: the CA-best neurons under inhibitory control. F, test series significantly
different from control series; †, significant difference between neuron types.
780
R. F. LUNDY AND R. NORGREN
Breadth of responsiveness
DISCUSSION
We have shown that electrical stimulation in the CeA
differentially controls gustatory neurons in the PBN. The
present findings are the first to demonstrate that a subcortical forebrain area can modulate tastant-evoked responses in
brain stem gustatory neurons. Prior studies have demonstrated that the lateral hypothalamus (LH) (Bereiter et al.
1980; Matsuo and Kusano 1984; Matsuo et al. 1984; Murzi
et al. 1986) and the gustatory cortex (GC) (Smith and Li
2000) modulate taste-responsive neurons in the nucleus of
the solitary tract (NST). Stimulation of the GC (Di Lorenzo
and Monroe 1992), but not the LH (Murzi et al. 1986), also
has been shown to influence gustatory cells in the PBN.
Descending activity was reported to be inhibitory, excitatory, or without effect on ongoing spontaneous discharge.
Although modulation of taste-evoked responses was not
assessed, these studies indicate that the stimulation sites in
the LH and the GC, which receive afferent gustatory information, generate descending activity in the same system.
Our data are consistent with these findings and extend them
by showing how a different forebrain region modulates
gustatory evoked responses in the PBN. Similar to the LH
and the GC, the CeA receives taste information from the
PBN, and the PBN, in turn, receives a reciprocal connection
from the CeA (Halsell 1992; Norgren 1976).
Coding
Given what is known about the central anatomy of the
gustatory system, both the site and parameters of electrical
stimulation were largely arbitrary. Nevertheless, we observed considerable effects, and the changes were coherent.
Amygdala stimulation inhibited the spontaneous activity
and the response to each taste stimulus in 18 of the 32
NaCl-best neurons and 14 of the 15 CA-best neurons. In
NaCl-best neurons, the degree of inhibition on spontaneous
activity and responses to the five sapid stimuli was similar,
but in CA-best neurons, inhibition was greatest for the most
effective stimuli (e.g., CA and NaCl). When CeA stimula-
Possible neural connections
The differential effect of CeA stimulation on NaCl-best PBN
neurons provides a hint of how forebrain activity might modulate the central gustatory system. The gustatory-evoked responses of different NaCl-best neurons isolated in the same
preparation were inhibited, facilitated, or unaffected during
electrical stimulation of the CeA. Modulation of spontaneous
activity might underlie the inhibitory effect on gustatory responses because the degree of inhibition was similar in the
presence and absence of a sapid stimulus on the tongue. In
contrast, with regard to NaCl, the excitatory effect was dependent on taste-evoked activity. This differential effect of CeA
stimulation on NaCl-best cells is further distinguished by the
suppressive effect of amiloride on NaCl responses. The inhibited gustatory neurons included both amiloride-sensitive and
amiloride-insensitive cells, while the facilitated gustatory neurons included only amiloride-sensitive cells. The excitatory
effect, but not the inhibitory effect, of CeA stimulation on
NaCl-evoked activity was disrupted by amiloride suppression
of NaCl responses. One interpretation is that a certain amount
of afferent activity might be required to engage the excitatory
descending influence and that this is normally achieved only
with above threshold concentrations of NaCl.
The only monosynaptic projections from the amygdala to the
brain stem originate in the CeA (Halsell 1992; Veening et al.
1984). Nevertheless, electrical stimulation cannot differentiate
between activation of intrinsic neurons and fibers of passage.
Using small infusions of an excitotoxin that does not activate
fibers of passage could test this possibility. If one assumes that
fibers of passage were involved, then the activation of the CeA
could have either influenced PBN neurons through direct syn-
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
The entropy measure (H value) ranges from 0 to 1. A
value of 0 corresponds to a neuron that was activated by
only one stimulus; a value of 1, to a neuron activated equally
by all stimuli. Amygdala stimulation reduced the entropy
measure of each response category (F1,70 ⫽ 9.1, P ⬍ 0.01,
Fig. 9A). Post hoc analysis of the main effect for neuron
type (F2,70 ⫽ 10.7, P ⬍ 0.01) revealed that the H value was
significantly lower for the NaCl-best cells compared with
the CA-best cells. Another way to measure change in responsiveness in taste neurons is the percentage of overall
evoked activity elicited by each of the sapid stimuli (Fig. 9,
B–D). For the inhibited NaCl-best neurons, CeA stimulation
increased the percentage of the response produced by NaCl
(60 –78%) and correspondingly decreased it for the other
stimuli (Fig. 9B; sucrose, 11 to ⫺1%; CA, 20 to 6%; QHCl,
9 to ⫺3%). Proportional responses did not differ significantly in the NaCl-best neurons augmented (Fig. 9C, F1,40 ⫽
0.0, P ⫽ 0.98), or in the CA-best neurons inhibited by CeA
stimulation (Fig. 9D, F1,96 ⫽ 0, P ⫽ 0.96).
tion facilitated responses in NaCl-best cells (5 of 32), the
effect was specific to that sapid stimulus; spontaneous activity and the responses to sucrose, CA, QHCl, and NaCl
mixed with amiloride were unaffected. The remaining NaClbest neurons (9 of 32) were not influenced by electrically
stimulating the CeA. The overall effect of CeA stimulation
was to sharpen the gustatory response profiles in PBN
neurons.
Specifically, the breadth of responses in NaCl-best and CAbest neurons was reduced during concurrent CeA stimulation,
indicating that these neurons increased their chemical selectivity. This shift in chemical sensitivity was most pronounced in
the NaCl-best neurons that were inhibited by forebrain stimulation. In this subset of neurons, sucrose, CA, and QHCl
became relatively less effective during CeA stimulation, and
the percentage of the total response profile produced by NaCl
increased from 60 to 78%. At least as far as the present
NaCl-best cells are concerned, the entropy measure during
CeA stimulation (0.45 ⫾ 0.05, mean ⫾ SE) was very near the
value calculated for NaCl-specific PBN cells in awake behaving rats (0.39 ⫾ 0.05) (Nishijo and Norgren 1990). In an
anesthetized preparation, activity in the CeA modulated NaClbest neurons in such a way that NaCl became a more salient
stimulus. In contrast, the inhibitory effect of CeA stimulation
in CA-best neurons disrupted the differential responsiveness to
CA and NaCl that is typical of this category. The small number
of sucrose-best neurons (n ⫽ 3) precludes any conclusion
concerning the influence of CeA activation.
FOREBRAIN STIMULATION AND GUSTATORY PROCESSING
781
might be to extract information from the incoming barrage
based on current demands. A few electrophysiological studies
have demonstrated that the induction of a sodium appetite
alters the sensitivity of the gustatory system to sodium (Contreras and Frank 1979; Nakamura and Norgren 1995; Tamura
and Norgren 1997). Whether sodium sensitivity is increased or
decreased, however, seems to depend on the method of inducing the sodium need state. For instance, dietary sodium deprivation reduced the responsiveness to NaCl in both chorda
tympani (Contreras and Frank 1979) and NST (Nakamura and
Norgren 1995) NaCl-best neurons. In contrast, a sodium appetite induced with the diuretic furosemide increased specifically
the response of NaCl-best NST neurons to NaCl (Tamura and
Norgren 1997). Our findings compliment these prior neurophysiological studies insofar as the activation of the CeA, a
region known to be responsive to changes in sodium balance,
also alters gustatory sensory processing of sodium. Activation
of the CeA inhibited the responsiveness of some NaCl-best
neurons to NaCl and other sapid stimuli (e.g., dietary sodium
deprivation), while in other NaCl-best neurons the response to
NaCl was increased selectively (e.g., furosemide sodium depletion).
Although the effect of this motivational state on gustatory
sensory processing in the PBN has not been examined, the
anatomical connections of the CeA are well suited to modulate gustatory information processing in the PBN based on
physiological demand. Despite a lack of knowledge about
how rostral brain structures might interpret this altered
gustatory information, the present results provide clues to a
neurophysiological relationship between the CeA and the
PBN in the control of NaCl intake. This centrifugal modulation might serve to increase the relative detectability and
motivational properties of the Na⫹ ion. Indeed, electrical
stimulation in the amygdala of awake-behaving rats has
been shown to alter saline preference (Gentil et al. 1971).
The direction of the change in preference, however, seems
to depend on the particular amygdaloid subnuclei that are
stimulated.
Implications for sodium appetite
Summary
The central nucleus of the amygdala (CeA) participates in
the maintenance of body fluid balance. For instance, c-fos
expression in the central and medial divisions of the amygdala
is increased by peritoneal dialysis–induced sodium depletion
(Johnson et al. 1999). This immunocytochemical index of
neural activation indicates that cells in these two amygdala
subnuclei responded to the change in sodium balance. In addition, bi-lateral lesions of the CeA disrupt the sodium appetite
that develops following furosemide (subcutaneous), DOCA
(subcutaneous), or renin (intracerebroventricular) injection
(Galaverna et al. 1991; Zardetto-Smith et al. 1994). The role of
the gustatory system is to carry the neural information that
signals the presence of the Na⫹ ion. Specifically, the amiloride-sensitive NaCl-best neurons are indispensable for the discrimination between sodium and nonsodium salts (Spector et
al. 1996) and for the expression of sodium appetite (Bernstein
and Hennessy 1987; Breslin et al. 1993; McCutcheon 1991).
One function of centrifugal projections to sensory nuclei
The present study demonstrated that a subcortical forebrain
area modulates pontine gustatory neurons. In 38 of 51 PBN
gustatory cells, descending activity generated in the CeA influenced taste-evoke responses. Specifically, taste responses were
inhibited in 33 cells and facilitated in another 5 cells. This centrifugal modulation increased the chemical selectivity of pontine
taste cells, particular with regard to NaCl-best cells. The NaCl
message transmitted through this subset of neurons was accentuated, which tends to mimic the changes in NST taste cell responsiveness produced by a motivational state, sodium appetite. Thus
the gustatory neural code is not rigid, but subject to modulation by
visceral signals and experience that likely involves centrifugal
input from the forebrain. In this context, we have identified one
forebrain area, the central nucleus of the amygdala, that participates in endocrine functions, receives afferent gustatory input, and
generates descending activity that alters gustatory sensory processing in the dorsal pons.
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
aptic contact or through an indirect projection via some other
forebrain region. As already mentioned, the PBN distributes
axons at least to the hypothalamus, amygdala, and bed nucleus
of the stria terminalis, and, in turn, receives projections from
each of these brain structures. Moreover, these more rostral
regions are connected with each other (see Norgren 1985 for
review; Halsell 1992; van der Kooy et al. 1984; Yamamoto et
al. 1984). The dissociation between these two alternative pathways might be tested by comparing gustatory-evoked responses in the PBN during CeA activation with and without
concurrent inactivation in each of these other rostral structures.
A final possibility is that the effects we observed in the PBN
were first established in the NST and then transmitted rostrally
to the PBN. In a prior study, stimulation in the LH modulated
NST gustatory neurons, but not those in the PBN (Murzi et al.
1986). Any inferences drawn from these earlier data must be
tempered by the small sample of PBN neurons tested (n ⫽ 12),
and the obvious fact that centrifugal influences on brain stem
gustatory neurons may differ between the LH and the CeA. A
more direct test would be to repeat the present study, but record
from gustatory neurons in the NST.
Other visceral sensory modalities also are subject to centrifugal modulation. Many cardiovascular-sensitive cells in both
the NST and PBN respond to electrical stimulation in the
hypothalamus and the amygdala (Cechetto and Calaresu 1983;
Cox et al. 1986; Mifflin et al. 1988; Silva-Carvalho et al. 1995).
In the case of hypothalamic stimulation, afferent activity
evoked in the NST by inflating a balloon in the descending
aorta or the carotid sinus was either inhibited, facilitated, or
unaffected (Silva-Carvalho et al. 1995). Interestingly, the efficacy of afferent input was facilitated in two NST neurons
without a synaptic response (e.g., excitatory postsynaptic potential) to the hypothalamic stimulation itself. The same types
of influence, exerted by corticofugal input, have been reported
in thalamic neurons that respond to auditory and somatosensory stimulation (Ghosh et al. 1994; He 1997; Villa et al.
1991). In the present study, electrical stimulation of the CeA
also had variable effects on somatosensory cells in the dorsal
pons (n ⫽ 15, data not shown). The spontaneous activity was
unaffected (n ⫽ 11), inhibited (n ⫽ 2), or facilitated (n ⫽ 2).
782
R. F. LUNDY AND R. NORGREN
This research was supported by National Institutes of Health (NIH) Grants
DC-00369, DC-00240, and MH-43787. R. Norgren was supported by NIH
Senior Scientist Award MH-00653.
REFERENCES
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017
BEREITER D, BERTHOUD HR, AND JEANRENAUD B. Hypothalamic input to brain stem
neurons responsive to oropharyngeal stimulation. Exp Brain Res 39: 33–39,
1980.
BERMUDEZ-RATTONI F AND MCGAUGH J. Insular cortex and amygdala lesions
differentially affect acquisition on inhibitory avoidance and conditioned
taste aversion. Brain Res 549: 165–170, 1991.
BERNSTEIN IL AND HENNESSY CJ. Amiloride-sensitive sodium channels and
expression of sodium appetite in rats. Am J Physiol Regulatory Integrative
Comp Physiol 253: R371–R374, 1987.
BERRIDGE KC, FLYNN FW, SCHULKIN J, AND GRILL HJ. Sodium depletion
enhances salt palatability in rats. Behav Neurosci 98: 652– 660, 1984.
BRESLIN PAS, SPECTOR AC, AND GRILL HJ. Chorda tympani section decreases
the cation specificity of depletion-induced sodium appetite in rats. Am J
Physiol Regulatory Integrative Comp Physiol 264: R319 –R323, 1993.
CECHETTO DF AND CALARESU FR. Parabrachial units responding to stimulation
of buffer nerves and forebrain in the cat. Am J Physiol Regulatory Integrative Comp Physiol R811–R819, 1983.
CHANG F-C AND SCOTT T. Conditioned taste aversions modify neural responses
in the rat nucleus tractus solitarius. J Neurosci 4: 1850 –1862, 1984.
CONTRERAS RJ AND FRANK ME. Sodium deprivation alters neural responses to
gustatory stimuli. J Gen Physiol 73: 569 –594, 1979.
CONTRERAS RJ AND HATTON GI. Gustatory adaptation as an explanation for
dietary-induced sodium appetite. Physiol Behav 15: 569 –576, 1975.
COX GE, JORDAN D, MORUZZI P, SCHWABER JS, SPYER KM, AND TURNER SA.
Amygdaloid influences on brain-stem neurones in the rabbit. J Physiol
(Lond) 381: 135–148, 1986.
DILORENZO PM AND MONROE S. Corticofugal input to taste-responsive units in
the parabrachial pons. Brain Res 29: 925–930, 1992.
GALAVERNA O, DELUCA LA JR, SCHULKIN J, YAO S-Z, AND EPSTEIN AN.
Deficits in NaCl ingestion after damage to the central nucleus of the
amygdala in the rat. Brain Res Bull 28: 89 –98, 1991.
GARCIA J, KIMELDORF DJ, AND KOELLING RA. Conditioned aversions to saccharin resulting from exposure to gamma radiation. Science 122: 157–158,
1955.
GENTIL CG, MOGENSON GJ, AND STEVENSON JAF. Electrical stimulation of
septum, hypothalamus, and amygdala and saline preference. Am J Physiol
220: 1172–1177, 1971.
GHOSH S, MURRAY GM, TURMAN AB, AND ROWE MJ. Corticothalamic influences on transmission of tactile information in the ventroposterolateral
thalamus of the cat: effect of reversible inactivation of somatosensory
cortical areas I and II. Exp Brain Res 100: 276 –286, 1994.
GRIGSON PS, SHIMURA T, REILLY S, AND NORGREN R. Ibotenic acid lesions of
the parabrachial nucleus disrupt learned taste aversions, but permit a learned
capsaicin aversion and a learned flavor preference (Abstract). Chem Senses
18: 564, 1993.
GRILL HJ. Introduction: physiological mechanisms in conditioned taste aversion. Ann NY Acad Sci 443: 67– 88, 1985.
GRILL H, SCHULKIN J, AND FLYNN FW. Sodium homeostasis in chronic decerebrate rats. Behav Neurosci 100: 536 –543, 1986.
HALSELL CB. Organization of parabrachial nucleus efferents to the thalamus
and amygdala in the golden hamster. J Comp Neurol 317: 57–78, 1992.
HE J. Modulatory effects of regional cortical activation on the onset responses
of the cat medial geniculate neurons. J Neurophysiol 77: 896 –908, 1997.
HOPKINS DA AND HOLSTEGE G. Amygdaloid projections to the mesencephalon,
pons and medulla oblongata in the cat. Exp Brain Res 32: 529 –547, 1978.
JHAMANDAS JH, PETROV T, HARRIS KH, VU T, AND KRUKOFF TL. Parabrachial
nucleus projection to the amygdala in the rat: electrophysiological and
anatomical observations. Brain Res Bull 39: 115–126, 1996.
JOHNSON AK, DE OLMOS J, PASTUSKOVAS CV, ZARDETTO-SMITH AM, AND
VIVAS L. The extended amygdala and salt appetite. Ann NY Acad Sci 877:
258 –280, 1999.
LOEWY AD AND SPYER KM. Central Regulation of Autonomic Function, edited
by Loewy AD and Spyer KM. New York: Oxford Univ. Press, 1990.
LUNDY RF JR AND CONTRERAS RJ. Gustatory neuron types in rat geniculate
ganglion. J Neurophysiol 82: 2970 –2988, 1999.
MATSUO R AND KUSANO K. Lateral hypothalamic modulation of the gustatorysalivary reflex in rats. J Neurosci 4: 1208 –1216, 1984.
MATSUO R, SHIMIZU N, AND KUSANO K. Lateral hypothalamic modulation of
oral sensory afferent activity in the nucleus tractus solitarius neurons of rats.
J Neurosci 4: 1201–1207, 1984.
MCCUTCHEON NB. Sodium deficient rats are unmotivated by sodium chloride
solutions mixed with the sodium channel blocker amiloride. Behav Neurosci
105: 764 –766, 1991.
MIFFLIN SW, SPYER KM, AND WITHINGTON-WRAY DJ. Baroreceptor inputs to
the nucleus tractus solitarius in the cat: modulation by the hypothalamus.
J Physiol (Lond) 399: 369 –387, 1988.
MURZI E, HERNANDEZ L, AND BAPTISTA T. Lateral hypothalamic sites eliciting
eating affect medullary taste neurons in rats. Physiol Behav 36: 829 – 834,
1986.
NACHMAN M. Taste preferences for sodium salts by adrenalectomized rats.
J Comp Physiol Psychol 55: 1124 –1129, 1962.
NACHMAN M AND ASHE JH. Learned taste aversion in rats as a function of
dosage, concentration, and route of administration. Physiol Behav 10: 73–
78, 1973.
NAKAMURA K AND NORGREN R. Sodium-deficient diet reduces gustatory activity in the nucleus of the solitary tract of behaving rats. Am J Physiol
Regulatory Integrative Comp Physiol 269: R647–R661, 1995.
NISHIJO H AND NORGREN R. Responses from parabrachial gustatory neurons in
behaving rats. J Neurophysiol 63: 707–724, 1990.
NORGREN R. Taste pathways to the hypothalamus and amygdala. J Comp
Neurol 166: 17–30, 1976.
NORGREN R. Taste and the autonomic nervous system. Chem Senses 10:
143–161, 1985.
NORGREN R AND PFAFFMANN C. The pontine taste area in the rat. Brain Res 91:
99 –117, 1975.
PAXINOS G AND WATSON C. The Rat Brain in Stereotaxic Coordinates. Sydney,
Australia: Academic, 1986.
RICHTER CP. Increased salt appetite in adrenalectomized rats. Am J Physiol
115: 155–161, 1936.
ROBERTS WW. [14C]Deoxyglucose mapping of first-order projections of the
lateral hypothalamus in the rat. J Comp Neurol 194: 617– 638, 1980.
ROTH S, SCHWARTZ M, AND TEITELBAUM P. Failure of lateral hypothalamic rats
to learn specific food aversions. J Comp Physiol Psychol 83: 184 –197, 1973.
RUGER J AND SCHULKIN J. Preoperative sodium appetite experience and hypothalamic lesions in rats. J Comp Physiol Psychol 94: 914 –920, 1980.
SAPER C AND LOEWY A. Efferent connections of the parabrachial nucleus in the
rat. Brain Res 197: 291–317, 1980.
SCALERA G, GRIGSON PS, AND NORGREN R. Excitotoxic lesions of the parabrachial nuclei prevent conditioned taste aversion and sodium appetite.
Behav Neurosci 109: 997–1008, 1995.
SCOTT TR AND PERROTTO RS. Intensity coding in pontine taste area: gustatory
information is processed similarly throughout rat’s brain stem. J Neurophysiol 44: 739 –750, 1980.
SHIMURA T, TANAKA H, AND YAMAMOTO T. Salient responsiveness of parabrachial neurons to the conditioned stimulus after the acquisition of taste
aversion learning in rats. Neuroscience 81: 239 –247, 1997.
SILVA-CARVALHO L, QAWID-MILNER MS, GOLDSMITH GE, AND SPYER KM.
Hypothalamic modulation of the arterial chemoreceptor reflex in the anaesthetized cat: role of the nucleus tractus solitarius. J Physiol (Lond) 487:
751–760, 1995.
SMITH DV AND LI CS. GABA-mediated corticofugal inhibition of tasteresponsive neurons in the nucleus of the solitary tract. Brain Res 858:
408 – 415, 2000.
SMITH DV AND TRAVERS JB. A metric for the breadth of tuning of gustatory
neurons. Chem Senses Flav 4: 215–229, 1979.
SPECTOR AC, GUAGLIARDO NA, AND ST. JOHN SJ. Amiloride disrupts NaCl
versus KCl discrimination performance: implications for salt taste coding in
rats. J Neurosci 16: 8115– 8122, 1996.
SPECTOR AC, NORGREN R, AND GRILL H. Parabrachial nucleus lesions impair
taste aversion learning in rats. Behav Neurosci 106: 147–161, 1992.
TAMURA R AND NORGREN R. Repeated sodium depletion affects gustatory
neural responses in the nucleus of the solitary tract of rats. Am J Physiol
Regulatory Integrative Comp Physiol 273: R1381–R1391, 1997.
VAN DER KOOY D, KODA LY, MCGINTY JF, GERFEN CR, AND BLOOM FE. The
organization of projections from the cortex, amygdala, and hypothalamus to
the nucleus of the solitary tract in rats. J Comp Neurol 224: 1–24, 1984.
VEENING JG, SWANSON LW, AND SAWCHENKO PE. The organization of projections from the central nucleus of the amygdala to brainstem sites involved in
central autonomic regulation: a combined retrograde transport-immunohistochemical study. Brain Res 303: 337–357, 1984.
FOREBRAIN STIMULATION AND GUSTATORY PROCESSING
VILLA AEP, ROUILLER EM, SIMM GM, ZURITA P, DERIBAUPIERRE Y, AND
DERIBAUPIERRE F. Corticofugal modulation of the information processing in
the auditory thalamus of the cat. Exp Brain Res 86: 506 –517, 1991.
YAMAMOTO T, YUYAMA N, KATO T, AND KAWAMURA Y. Gustatory responses
of cortical neurons in rats. I. Response characteristics. J Neurophysiol 51:
616 – 635, 1984.
783
YASOSHIMA Y, SHIMURA T, AND YAMAMOTO T. Single unit responses of the
amygdala after conditioned taste aversion in conscious rats. NeruoReport 6:
2424 –2428, 1995.
ZARDETTO-SMITH AM, BELTZ TG, AND JOHNSON AK. Role of the central
nucleus of the amygdala and bed nucleus of the stria terminalis in experimentally-induced salt appetite. Brain Res 645: 123–134, 1994.
Downloaded from http://jn.physiology.org/ by 10.220.32.247 on June 18, 2017