The effects of noradrenergic activation of the nucleus tractus solitarius on memory and in potentiating norepinephrine release in the amygdala.

Although it is known that norepinephrine (NE) modulates memory by acting on limbic areas, few studies describe how structures supplying NE to the limbic system such as the nucleus tractus solitarius (NTS) contribute to this process. The present study examined the effects on memory of activating the NE pathway between the NTS and the amygdala (AMYG). Rats received buffer or the β-noradrenergic agonist clenbuterol (CLN; 10, 50, or 100 ng/0.5 μl) into the NTS after footshock training in a Y-maze discrimination task. Infusion of 100 ng CLN significantly improved memory when retention was tested in the absence or presence of cues associated with the footshock. Experiment 2 used in vivo microdialysis to determine whether the mnemonic effects of CLN are mediated by influencing NE output in the AMYG. Subjects were given an intra-NTS infusion of CLN or phosphate buffered saline, footshock (0.8 mA, 1 s) and injected with epinephrine (EPI; 0.3 mg/kg ip) or saline. CLN or EPI injection produced a significant increase in NE sampled from the AMYG. These findings indicate that activation of NTS neurons that project to and release NE in the AMYG modulates memory storage processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Norepinephrine release in the amygdala after systemic injection of epinephrine or escapable footshock: contribution of the nucleus of the solitary tract

Several findings based largely on lesions and drug manipulations within the amygdala suggest that norepinephrine (NE) systems in the amygdala contribute to enhancement of memory processes by epinephrine (EPI). However, no studies to date have directly measured changes in the release of NE in the amygdala after EPI injection. In Experiment 1, in vivo microdialysis was used to assess amygdala NE release after systemic injection of saline, EPI (0.1 or 0.3 mg/kg), and administration of an escapable footshock (0.8 mA, 1 s). Both doses of EPI produced a significant elevation in NE release that persisted for up to 60 min. In Experiment 2, the local anesthetic lidocaine (2%) was infused (0.5 microl) into the nucleus of the solitary tract (NTS) immediately before injection of 0.3 mg/kg EPI. The EPI-induced elevation in amygdala NE release observed in Experiment I was attenuated by inactivation of the NTS. These findings indicate that systemic injection of EPI increases release of NE in the amygdala and suggest that the effects are mediated in part by activation of brainstem neurons in the NTS that project to the amygdala.     

Posttraining intra-basolateral amygdala scopolamine impairs food- and amphetamine-induced conditioned place preferences.

The present study investigated the role of cholinergic muscarinic receptor function within the basolateral amygdala memory in the consolidation of conditioned place preference (CPP) memory. Adult male Long-Evans rats were confined to treatment- or nontreatment-paired compartments for 30 min on 4 alternating days. After training, rats received intrabasolateral amygdala infusions of scopolamine (2.5 μg or 5.0 μg/0.5 μl) or saline. The rats were then given a 20-min test session, and the time spent in each of the compartments was recorded. Immediate posttraining (but not delayed 2 hr) scopolamine (5.0 μg) blocked acquisition of food- and amphetamine-induced CPPs. The findings indicate a time-dependent role for basolateral amygdala muscarinic receptors in memory consolidation underlying CPPs for natural and drug rewards. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The noradrenergic system of the amygdala and aversive information processing.

In 4 experiments, 113 water-deprived male Long-Evans rats were trained to drink in a passive avoidance apparatus. After reaching a latency criterion, Ss were given a single 3-sec, 3-mA footshock. Immediately or 12 hrs after footshock, Ss were given intracranial injections of vehicular saline, norepinephrine (NE), propranolol, or dopamine (DA) into the amygdala, internal capsule, lateral ventricles, or caudate-putamen. Ss were tested for passive avoidance at 30 min or 24 hrs following footshock. No memory deficits were seen as a consequence of short-term retention or because of proactive or toxicity effects. Retention deficits were seen in the 24-hr test only in Ss injected with NE in the amygdala, internal capsule, or lateral ventricles. However, qualitative differences in stress-indicative behaviors were noted in the NE groups and in the DA-amygdala Ss. Results suggest that the noradrenergic system of the amygdala is involved in the long-term processing of the emotional attributes of aversive information. (66 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Excitatory amino-acid receptors contribute to carotid sinus and vagus nerve evoked excitation of neurons in the nucleus of the tractus solitarius

To determine the role of excitatory amino-acid (EAA) receptors in afferent evoked excitation of neurons in the nucleus of the solitarius (NTS), responses of NTS neurons to activation of visceral afferent inputs were examined before and during iontophoretic application of the broad spectrum EAA receptor antagonist kynurenate (KYN). Iontophoretic application of KYN, at doses which attenuated glutamate but not substance P or acetylcholine evoked discharge, inhibited carotid sinus nerve (CSN) and vagus nerve evoked discharge. KYN attenuation of evoked responses was similar whether the evoked input was monosynaptic (CSN evoked discharge reduced by 50 +/- 6% (mean +/- SE; n = 5); vagus nerve evoked discharge reduced by 45 +/- 4%, n = 6) or polysynaptic (CSN evoked discharge reduced by 48 +/- 6%, n = 6; vagus nerve evoked discharge reduced by 43 +/- 3%, n = 8). Spontaneous action potential discharge rate was reduced during KYN iontophoresis in 6 cells (1.8 +/- 0.4 spikes/s vs. 0.7 +/- 0.2 spikes/s). Iontophoretic application of a structural analogue of KYN which has no EAA receptor antagonist properties, xanthurenic acid, had no effect on glutamate, CSN or vagus nerve evoked discharge. Iontophoretic application of KYN reduced the action potential discharge evoked by activation of the carotid body chemoreceptors by 52 +/- 2% in 5 cells tested. The results demonstrate that excitatory amino-acid receptors are involved in visceral afferent evoked activation of NTS neurons. Furthermore, since both mono- and poly-synaptic inputs were attenuated, these receptors appear to be utilized at multiple levels of afferent integration within NTS.     

Hippocampal–prefrontocortical circuits: PKA inhibition in the prefrontal cortex impairs delayed nonmatching in the radial maze in rats.

Recent findings implicate the prefrontal cortex (PFC) and, in particular, frontocortical dopamine acting at D1-like receptors, in working memory. However, the mechanisms underlying this function of dopamine remain unknown. The present studies evaluated the hypothesis that dopamine contributes to working memory through its action on the 2nd messenger cyclic 3',5'-adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA). Thus, rats were trained to perform random foraging or delayed (30 min) nonmatching-to-position (delayed win-shift) tasks on the radial maze. With hippocampal output to the frontal cortex disconnected by injecting lidocaine (20 μg/0.5 μl) unilaterally into the ventral subiculum, contralateral frontocortical injections of lidocaine (20 μg/0.5 μl) or the D1-like dopamine receptor antagonist SCH 23390 (0.5 μg/0.5 μl) impaired delayed win-shift but not random foraging, replicating previous findings. In similarly disconnected rats, frontocortical injections of the PKA inhibitor Rp-cAMPS (5.0 and 10.0, but not 1.0, μg/0.5 μl) selectively impaired delayed nonmatching-to-position. Results suggest that activation of the cAMP-PKA pathway by dopamine acting at D1-like receptors in the frontal cortex is necessary for working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Glutamatergic influences on the nucleus paragigantocellularis: Contribution to performance in avoidance and spatial memory tasks.

Stimulation of the locus coeruleus (LC) and the subsequent release of norepinephrine contribute to memory consolidation processes. Excitatory input to the LC is derived primarily from neurons in the nucleus paragigantocellularis (PGi). The authors examined the effects of activating the pathway between PGi and the LC on memory. Rats received vehicle or the excitatory amino acid glutamate (25, 50, or 100 nmol/0.5 μl) into PGi after training in an inhibitory avoidance (IA) or delayed matching-to-sample (DMS) task. Rats given the 100-nmol dose had significantly longer retention latencies on a 48-hr IA retention test. Rats treated with the 50- or 100-nmol dose made significantly more correct responses than controls on an 18-hr DMS retention test. Results suggest that encoding and storage of memory for emotional and spatial events may be enhanced by activation of neuronal circuits afferent to the LC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association between the amygdala and nucleus of the solitary tract in mu-opioid induced feeding in the rat

The central nucleus of the amygdala (CNA) and the nucleus of the solitary tract (NTS) are important in the regulation of ingestive behavior. We evaluated whether opioid-opioid signaling between the CNA and rostral NTS (rNTS) affect feeding behavior. To test this, rats were doubly cannulated with one cannula placed in the rNTS and one cannula in the CNA, allowing for co-administration of an opioid agonist into one site and an opioid antagonist into the other. Tyr-D-Ala-Gly-(me) Phe-Gly-ol (DAMGO) (2 nmol) injected into the CNA (CNA DAMGO) increased feeding more than two-fold compared to the vehicle-injected rats. This increase in food intake was blocked when doses of 26.5 and 79 nmol of naltrexone (NTX) were injected into the rNTs. In the reverse situation, rNTS DAMGO increased food intake above control levels, and CNA NTX blocked DAMGO-induced feeding when administrated in doses of 26.5 and 79 nmol. This suggests that a bi-directional opioid-opioid signaling pathway exists between the CNA and the rNTS which influences feeding via mu-opioid receptors.     

Reversible lesions of the nucleus of the solitary tract attenuate the memory-modulating effects of posttraining epinephrine.

Male rats implanted with cannula tips placed above the nucleus of the solitary tract (NTS) were trained to obtain food pellets placed in 2 arms of a Y-maze and then given a footshock in 1 arm of the maze. Ss then received bilateral injections of lidocaine or buffer into the NTS and peripheral injections of saline or epinephrine (0.01 or 0.05 mg/kg, intraperitoneally [ip]). Two tests were given 24 and 48 hrs after training to assess retention in the presence and absence of contextual cues (the stainless steel floor) associated with the footshock training trial. Epinephrine (0.05 mg/kg) produced a significant enhancement in retention, which was attenuated by injections of lidocaine into the NTS. These findings indicate that the NTS is involved in mediating the memory-modulating effects of peripheral epinephrine and that such effects are initiated at least in part by activation of vagal afferents projecting to the NTS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of posttraining injection of cholinergic agonists and antagonists into the amygdala on retention of passive avoidance training in rats.

144 adult male Long-Evans rats were given a single footshock while licking a water tube and tested 24 hrs later for retention of the footshock experience. A single bilateral injection of a subseizure dose of physostigmine into the amygdala applied immediately but not 18 hrs after the footshock impaired retention. This effect appeared to be somewhat localized, as physostigmine injected into the hippocampus or lateral ventricles did not disrupt retention. Conversely, a subseizure dose of atropine sulfate into the amygdala, given immediately or 18 hrs after the footshock did not impair retention. Atropine injected concurrently with physostigmine into the same amygdaloid loci counteracted a potential physostigmine-induced retention deficit. Injection of carbachol into the amygdala also impaired retention; however, carbachol precipitated seizures and possibly exerted proactive consequences on performance. The time-dependent nature of the deficit following physostigmine is consistent with the view that injection of cholinergic agonists into the amygdala disrupts memory for the footshock experience. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine transmission in the amygdala modulates surprise in an aversive blocking paradigm.

Learning about predictive relationships depends on surprise. For example, in Kamin's blocking paradigm learning about the association between one stimulus (X) and a footshock is attenuated when X→footshock training occurs in the presence of a good predictor (A) of that footshock. Establishing the neural processes that underlie this effect has generated considerable interest in recent years. Here, an infusion of the dopamine antagonist cis-(z)-Flupenthixol into the amygdala prior to compound (AX) conditioning attenuated the blocking effect, but had no effect on controls. This effect of dopamine antagonism in the amygdala immediately prior to compound conditioning was obtained irrespective of whether infusions occurred prior to the first, second or both compound conditioning trials. These results provide evidence for the involvement of amygdaloid dopamine in regulating surprise in fear and therefore predictive learning via a direct outcome processing mechanism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spared retention of inhibitory avoidance learning after posttraining amygdala lesions.

Previous findings indicate that the memory-impairing effects of posttraining amygdala lesions are attenuated by increasing the number of training trials given prior to the induction of the lesion. The aim of this experiment was to determine whether the degree of impairment is also influenced by the footshock intensity used during training. Rats were given 1 trial of inhibitory avoidance (IA) training with either no footshock or a footshock at 1 of 3 intensities. Sham or neurotoxic amygdala lesions were induced 1 week later. On a retention test performed 4 days after surgery, the performance of all amygdala-lesioned rats given footshock training, including those given the lowest training footshock, was better than that of amygdala-lesioned rats given no training footshock. These findings of preserved retention of IA learning in rats given posttraining amygdala lesions do not support a general hypothesis that the amygdala is a locus of permanent changes underlying aversively motivated learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Associative structure of fear memory after basolateral amygdala lesions in rats.

The authors have recently demonstrated that rats with basolateral amygdala (BLA) lesions acquire Pavlovian fear conditioning after overtraining. However, it is not known whether the associative basis of Pavlovian fear memory acquired by rats with BLA lesions is similar to that of intact rats. Associations are typically formed between the conditional (CS) and unconditional (US) stimuli (stimulus-stimulus; S-S), although it is possible for stimuli to enter into association with the responses they produce (stimulus-response; S-R). Indeed, the central nucleus of the amygdala, which is essential for fear conditioning in rats with BLA lesions, may mediate S-R associations in some Pavlovian tasks. The authors therefore used a postconditioning US inflation procedure (i.e., exposure to intense footshock USs) to assess the contribution of S-S associations to fear conditioning after overtraining in rats with BLA lesions. In Experiment 1, intact rats that were overtrained and later inflated displayed elevated freezing levels when tested, indicating that S-S associations contribute to overtrained fear memories. Interestingly, neither neurotoxic BLA lesions nor temporary inactivation of the BLA during overtraining prevented the inflation effect (Experiment 2 and 3, respectively). These results reveal that S-S associations support Pavlovian fear memories after overtraining in both intact rats and rats with BLA lesions, and imply that the central nucleus of the amygdala encodes CS-US associations during fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttraining electrical stimulation of vagal afferents with concomitant vagal efferent inactivation enhances memory storage processes in the rat

Peripherally administered or released substances that modulate memory storage, but do not freely enter the brain, may produce their effects on memory by activating peripheral receptors that send messages centrally through the vagus nerve. Indeed, vagus nerve stimulation enhances memory performance, although it is unclear whether this effect is due to the activation of vagal afferents or efferents. To eliminate the possible influence of descending fibers on memory storage processes, rats were implanted with cuff electrode/catheter systems along the left cervical vagus. Forty-eight hours following surgery, each animal received a 3. 0-microliter infusion (1.0 microliter/min) of either lidocaine hydrochloride (75.0 mM) or isotonic saline below the point of stimulation. Animals were then trained 10 min later on an inhibitory-avoidance task with a 0.75-mA, 1.0-s foot shock. Sham stimulation or vagus nerve stimulation (0.5-ms biphasic pulses; 20.0 Hz; 30 s; 0.2, 0.4, or 0.8 mA) was administered immediately after training. Memory, tested 24 h later, was enhanced by stimulation whether descending vagus nerve fibers were inactivated or not. Both lidocaine- and saline-infused groups showed an intensity-dependent, inverted-U-shaped pattern of retention performance, with the greatest effect observed for 0.4 mA (U = 9, p < .05, and U = 7, p < .01, respectively). Additionally, animals that received lidocaine infusions, but no vagus nerve stimulation, showed impaired memory compared to the performance of saline-infused control animals (U = 11, p < .05). Together, these findings suggest that vagal afferents carry messages about peripheral states that lead to the modulation of memory storage and that the memory-enhancing effect produced by vagus nerve stimulation is not mediated via the activation of vagal efferents.     

Medullary pathways of cardiovascular responses to 5-HT2 and 5-HT3 receptor stimulation in the rat nucleus tractus solitarius

As previously found for the baroreceptor reflex, microinjection of kynurenic acid (KYN, 2 nmol), a glutamate receptor antagonist, into the caudal ventrolateral medulla (CVL) blocked the hypotension and bradycardia elicited by microinjections of a 5-HT2 receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI, 0.5 pmol) into the nucleus tractus solitarius (NTS). In addition, as previously observed with the sympathetic chemoreflex response, microinjections of KYN into the RVI, blocked the increase in blood pressure elicited by microinjections of 1-m-(chlorophenyl)-biguanide (1200 pmol), a 5-HT1 receptor agonist, into the NTS. These results suggest that medullary pathways involved in the responses to 5-HT2 and 5-HT3 receptor stimulation in the NTS are similar to those that mediate the baroceptor and chemoreceptor reflex responses, respectively.     

Central implants of dilute estradiol enhance the satiety effect if CCK-8.

The following studies evaluated whether direct placement of estradiol into different brain areas could increase the satiating potency of CCK in female rats. In Experiment 1, estradiol implants in the PVN, but not in the VMN or third ventricle, significantly enhanced the satiety actions of CCK (5.0 μg/kg). In Experiment 2, a lower dose of CCK (0.5 μg/kg) suppressed food intake in females with estradiol implants in the PVN but not in animals with implants in the VMN or preoptic area. In both experiments, estradiol implants in the PVN significantly lowered food intake and body weight during the 2-day period of hormone treatment. Implants in other areas had no significant effects on feeding or body weight. These data support the hypothesis that the satiety effect of CCK is enhanced by estradiol and suggest that the PVN is involved in the interaction between CCK and estradiol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the bed nucleus of the stria terminalis block sensitization of the acoustic startle reflex produced by repeated stress, but not fear-potentiated startle

1. The effects of lesions of the bed nucleus of the stria terminalis (BST) on the acquisition of conditioned fear were examined. In Experiment 1, BST lesions did not block acquisition of fear-potentiated startle to an explicit visual conditioned stimulus (CS) over 20 days of training. However, BST lesions blocked a gradual elevation in baseline startle also seen over the course of training. 2. The gradual increase in baseline startle was replicated in Experiment 2 without the presence of an explicit CS, using unoperated subjects. Experiment 2 showed that the elevation was due to repetitive exposure to shock, because unshocked control subjects did not show any elevation over sessions. 3. In Experiment 3, lesions of the BST did not disrupt rapid sensitization of the startle reflex by footshock, showing that different neural substrates underlie sensitization of startle by acute and chronic exposure to footshock. 4. These data indicate that the BST, despite its anatomical continuity with the amygdala, is not critically involved in the acquisition of conditioned fear to an explicit CS. Nevertheless, the BST is involved in mediating a stress-induced elevation in the startle reflex. This suggests that the BST and the CeA, which constitute part of the "extended amygdala" have complementary roles in responses to stress.     

Cardiovascular effects of nitric oxide and adenosine in the nucleus tractus solitarii of rats

It has been shown that nitric oxide (NO) is synthesized in the central nervous system as well as in vascular endothelial cells. We recently reported that NO was involved in central cardiovascular regulation, modulated the baroreflex, and was involved in a reciprocal release with excitatory amino acids in the nucleus tractus solitarii (NTS) of rats. We also reported previously that adenosine increased the release of glutamate in the NTS. The purpose of the present study was to investigate the possible interaction of NO and adenosine in the NTS. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure was monitored intra-arterially. Unilateral microinjection of L-arginine (3.3 nmol/60 nL) into the NTS produced decreases in blood pressure and heart rate. Microinjection of adenosine (2.3 nmol/60 nL) also produced depressive and bradycardic effects. These cardiovascular effects were attenuated by prior administration of the specific adenosine receptor antagonist DPSPX (0.92 nmol). Similarly, prior administration of NO synthase inhibitor NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester significantly attenuated the depressive and bradycardic effects of adenosine. These results demonstrate a reciprocal attenuation of adenosine receptor antagonist and NO synthase inhibitor on L-arginine and adenosine responses, respectively, in the NTS and implicate an interaction between NO and adenosine in central cardiovascular regulation.     

Ascending projections from the area postrema and the nucleus of the solitary tract of Suncus murinus: anterograde tracing study using Phaseolus vulgaris leucoagglutinin

Suncus murinus (suncus) is a new experimental animal model for research on the mechanisms underlying emesis. In the present study, we examined the ascending projections from the area postrema (AP) and the nucleus of the solitary tract (NTS) in suncus based on anterograde transport of phaseolus vulgaris leucoagglutinin. The AP projected heavily to the dorsal vagal complex, especially in the commissural and medial subnuclei of the NTS, and the dorsal motor nucleus of the vagus. Some ascending fibers from the AP projected bilaterally to the parabrachial nucleus (Pb), but no labeling was observed rostral to this area. In contrast, the NTS had extensive projections as far as the basal forebrain. The NTS projections were observed in the AP, ventrolateral reticular formation including the nucleus ambiguus, A5 noradrenergic area, locus coeruleus, Pb, and central gray matter of the midbrain. At the level of the diencephalon, the NTS projections were seen in the dorsomedial, lateral, paraventricular, periventricular, supraoptic, retrochiasmatic and arcuate nuclei of the hypothalamus, in addition to the paraventricular nucleus of the thalamus. Terminal fields within the basal forebrain were also shown to include the medial preoptic area, the bed nucleus of the stria terminalis, the substantia innominata and the ventral pallidum. The results indicated that the neurological relationship between the chemo- and/or barosensitive systems including the trigger of the emetic response and the general viscerosensory and/or -motor systems may exist also in the suncus.     

Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus.

[Correction Notice: An erratum for this article was reported in Vol 114(2) of Behavioral Neuroscience (see record 2007-17251-001). The captions for Figure 4 (p. 70) and Figure 5 (p. 72) were printed incorrectly. The caption used for Figure 4 should appear under Figure 5, and the caption used for Figure 5 should appear under Figure 4.] The role of the dorsal hippocampus in contextual fear conditioning was investigated with a contextual blocking paradigm. In Experiment 1, rats were given pairings of a light conditioned stimulus (CS) and footshock after preexposure either to footshock or to the context alone. The group preexposed to footshock showed poorer fear conditioning to the light CS, as measured by the fear-potentiated startle reflex. In Experiment 2, a group preexposed to footshock in the same context showed poorer fear conditioning to the light CS than did a group preexposed to footshock in a different context, indicating contextual blocking of fear-potentiated startle. In Experiment 3, lesions of the dorsal hippocampus had no effect on contextual blocking, even though contextual freezing was disrupted. The sparing of contextual blocking indicated that contextual memory was intact following hippocampal lesions, despite the disruption of contextual freezing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)