Differential effects of muscarinic receptor blockade in prelimbic cortex on acquisition and memory formation of an odor-reward task

The present experiments determined the consequences of blocking muscarinic cholinergic receptors of the prelimbic (PL) cortex in the acquisition and retention of an odor-reward associative task. Rats underwent a training test (five trials) and a 24-h retention test (two retention trials and two relearning trials). In the first experiment, rats were bilaterally infused with scopolamine (20 or 5 microg/site) prior to training. Although scopolamine rats showed acquisition equivalent to PBS-injected controls, they exhibited weakened performance in the 24-h retention test measured by number of errors. In the second experiment, rats were injected with scopolamine (20 microg/site) immediately or 1 h after training and tested 24 h later. Scopolamine rats injected immediately showed severe amnesia detected in two performance measures (errors and latencies), demonstrating deficits in retention and relearning, whereas those injected 1 h later showed good 24-h test performance, similar to controls. These results suggest that muscarinic transmission in the PL cortex is essential for early memory formation, but not for acquisition, of a rapidly learned odor discrimination task. Findings corroborate the role of acetylcholine in consolidation processes and the participation of muscarinic receptors in olfactory associative tasks.     

Complex effects of NMDA receptor antagonist APV in the basolateral amygdala on acquisition of two-way avoidance reaction and long-term fear memory

Although much has been learned about the role of the amygdala in Pavlovian fear conditioning, relatively little is known about an involvement of this structure in more complex aversive learning, such as acquisition of an active avoidance reaction. In the present study, rats with a pretraining injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic acid (APV), into the basolateral amygdala (BLA) were found to be impaired in two-way active avoidance learning. During multitrial training in a shuttle box, the APV-injected rats were not different from the controls in sensitivity to shock or in acquisition of freezing to contextual cues. However, APV injection led to impaired retention of contextual fear when tested 48 h later, along with an attenuation of c-Fos expression in the amygdala. These results are consistent with the role of NMDA receptors of the BLA in long-term memory of fear, previously documented in Pavlovian conditioning paradigms. The APV-induced impairment in the active avoidance learning coincided with deficits in directionality of the escape reaction and in attention to conditioned stimuli. These data indicate that normal functioning of NMDA receptors in the basolateral amygdala is required during acquisition of adaptive instrumental responses in a shuttle box but is not necessary for acquisition of short-term contextual fear in this situation.     

Neuronal representation of conditioned taste in the basolateral amygdala of rats

Animals develop robust learning and long lasting taste aversion memory once they experience a new taste that is followed by visceral discomfort. A large body of literature has supported the hypothesis that basolateral amygdala (BLA) plays a critical role in the acquisition and extinction of such conditioned taste aversions (CTA). Despite the evidence that BLA is crucially engaged during CTA training, it is unclear how BLA neural activity represents the conditioned tastes. Here, we incorporated a modified behavioral paradigm suitable for single unit study, one which utilizes a sequence of pulsed saccharin and water infusion via intraoral cannulae. After conditioning, we investigated BLA unit activity while animals experience the conditioned taste (saccharin). Behavioral tests of taste reactivity confirmed that the utilized training procedure produced reliable acquisition and expression of the aversion throughout test sessions. When neural activity was compared between saccharin and water trials, half of the recorded BLA units (77/149) showed differential activity according to the types of solution. 76% of those cells (29/38) in the conditioned group showed suppressed activity, while only 44% of taste reactive cells (17/39) in controls showed suppressed activity during saccharin trials (relative to water trials). In addition, the overall excitability of BLA units was increased as shown by altered characteristics of burst activity after conditioning. The changes in BLA activity as a consequence of CTA were maintained throughout test sessions, consistent with the behavioral study. The current study suggests that the neuronal activity evoked by a sweet taste is altered as a consequence of CTA learning, and that the overall change might be related to the learning induced negative affect.     

Basolateral amygdala lesions do not prevent memory of context-footshock training

The present studies examined the effects of basolateral amygdala (BLA) lesions induced prior to or after context-footshock training on 48-h memory, using several retention measures. In experiment 1, male Sprague-Dawley rats with bilateral BLA lesions (NMDA, 12.5 mg/mL, 0.2 μL) were given footshock training in one compartment of a two-compartment alley. Rats were habituated to the alley and 24 h later were given two footshocks in the shock compartment. Retention was tested 48 h later, using latency to enter the shock compartment and time spent freezing as measures of memory. Two days later, they were tested again and received a footshock on each re-entry of the shock compartment prior to remaining in the safe compartment for 200 consecutive seconds. The BLA lesions did not block retention as assessed by freezing or number of re-entries of the shock compartment. In experiment 2, no prior habituation was given, and only one footshock was used for the training. BLA lesions did not block retention, as indicated by latencies to enter the shock compartment on a 48-h test or by number of entries of the shock compartment. Experiment 3 examined the effects of the GABA_A agonist muscimol infused into the BLA prior to the 48-h retention test. The muscimol infusions decreased retention test entrance latencies but did not block retention as assessed by the number of subsequent entries of the shock compartment. These findings provide additional evidence that an intact BLA is not required for the acquisition or retention of context-footshock training.     

Enhancement of inhibitory avoidance and conditioned taste aversion memory with insular cortex infusions of 8-Br-cAMP: involvement of the basolateral amygdala

There is considerable evidence that in rats, the insular cortex (IC) and amygdala are involved in the learning and memory of aversively motivated tasks. The present experiments examined the effects of 8-Br-cAMP, an analog of cAMP, and oxotremorine, a muscarinic agonist, infused into the IC after inhibitory avoidance (IA) training and during the acquisition/consolidation of conditioned taste aversion (CTA). Posttraining infusion into the IC of 0.3 microg oxotremorine and 1.25 microg 8-Br-cAMP enhanced IA retention. Infusions of 8-Br-cAMP, but not oxotremorine, into the IC enhanced taste aversion. The experiments also examined whether noradrenergic activity in the basolateral amygdala (BLA) is critical in enabling the enhancement of CTA and IA memory induced by drug infusions administered into the IC. For both CTA and IA, ipsilateral infusions of beta-adrenergic antagonist propranolol administered into the BLA blocked the retention-enhancing effect of 8-Br-cAMP or oxotremorine infused into the IC. These results indicate that the IC is involved in the consolidation of memory for both IA and CTA, and this effect requires intact noradrenergic activity into the BLA. These findings provide additional evidence that the BLA interacts with other brain regions, including sensory cortex, in modulating memory consolidation.     

Inhibiting PKMζ reveals dorsal lateral and dorsal medial striatum store the different memories needed to support adaptive behavior

Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or just coordinate the learning and retention of these solutions by other brain regions. To address this issue, we developed a two-lever concurrent variable-interval reinforcement operant conditioning task and used it to assess the trained rat's sensitivity to contingency shifts. Consistent with the view that these two regions make different contributions to actions and habits, injecting the NMDA antagonist DL-AP5 into the DMS just prior to the shift impaired the rat's performance but enhanced performance when injected into the DLS. To determine if these regions support memory content, we first trained rats on a biased concurrent schedule (Lever 1: VI 40" and Lever 2: VI 10"). With the intent of "erasing" the memory content stored in striatum, after this training we inhibited the putative memory-maintenance protein kinase C isozyme protein kinase Mζ (PKMζ). Infusing zeta inhibitory peptide (ZIP) into the DLS enhanced the rat's ability to adapt to the contingency shift 2 d later, whereas injecting it into the DMS had the opposite effect. Infusing GluR2(3Y) into the DMS 1 h before ZIP infusions prevented ZIP from impairing the rat's sensitivity to the contingency shift. These results support the hypothesis that the DMS stores information needed to support actions and the DLS stores information needed to support habits.     

Postacquisition injection of tetrodotoxin into the parabrachial nuclei elicits partial disruption of passive avoidance reaction in rats.

The recent discovery that post-trial functional blockade of the parabrachial nuclei by intracerebral injection of 10 ng tetrodotoxin (TTX) disrupts acquisition of conditioned taste aversion (CTA) (Ivanova & Bures, 1990a,b) has prompted attempts to ascertain the role of this structure in other types of inhibitory learning. In Experiment 1, rats with implanted parabrachial cannulae were trained in a step-through avoidance task and received bilateral TTX (2 x 10 ng) immediately after the acquisition trial; they displayed significantly weakened avoidance of the shock compartment 2 days later. In Experiment 2, rats were anesthetized with pentobarbital (50 mg/kg) immediately after passive avoidance acquisition and received parabrachial TTX 15 min later; whereas anesthesia alone left the passive avoidance reaction (PAR) unaffected, TTX elicited similar disruption as in unanesthetized animals. In Experiment 3, TTX was injected in anesthetized animals 0, 1, 2, or 4 days after PAR acquisition. The amnesic effect was significant when the acquisition-TTX delay had been prolonged to 24 but not to 48 or 96 h. Since CTA is disrupted by reversible blockade of parabrachial nuclei and of the adjacent reticular formation elicited up to 4 days after acquisition (Ivanova & Bures, 1990b), PAR seems to be impaired to a lesser degree and for a shorter time than CTA by similar TTX treatment.     

Intra-amygdala infusion of the protein kinase Mzeta inhibitor ZIP disrupts foreground context fear memory

Protein kinase Mzeta has been the subject of much recent interest, as it is the only molecule currently identified to maintain memory. Despite the wealth of studies investigating PKMζ in memory, questions remain about which types of memory PKMζ supports. Further, it is unclear how long the inhibitor of PKMz, ζ-pseudosubstrate inhibitory peptide (ZIP) remains in the brain after infusion. Here, we demonstrate that foreground context fear memory requires PKMζ activity in the amygdala. We also show that ZIP is fully cleared from the brain by 24h after infusion. These data contribute to a growing body of literature that demonstrates that PKMζ plays a key role in maintaining amygdala-dependent memory and provides new information about the degradation timecourse of the most commonly used inhibitor of PKMζ, ZIP.     

Retrieval does not induce reconsolidation of inhibitory avoidance memory

It has been suggested that retrieval during a nonreinforced test induces reconsolidation instead of extinction of the mnemonic trace. Reconsolidation would preserve the original memory from the labilization induced by its nonreinforced recall through a hitherto uncharacterized mechanism requiring protein synthesis. Given the importance that such a process would have in terms of maintaining, as part of the animal behavioral repertoire, a learned response that has been devalued by experience, we analyzed its existence for the memory associated with a one-trial, step-down inhibitory avoidance task (IA), a memory whose consolidation and extinction require protein synthesis in the CA1 region of the dorsal hippocampus (CA1) and involve the participation of the basolateral amygdala (BLA) and entorhinal cortex (ENT). Rats were trained in IA, and 24 h later they were submitted either to a pure reactivation session (retrieval without stepping down), which was unable by itself to initiate extinction of the avoidance response, or to a second training session. Fifteen minutes before or 3 h after either the reactivation or the retraining sessions, animals were infused with the protein synthesis inhibitor anisomycin (ANI) into CA1, BLA, or ENT. Contrary to the prediction of the reconsolidation hypothesis, none of these treatments affected subsequent memory retention. Because reconsolidation is regarded to be a direct consequence of retrieval, one would expect that, when given before a retention test or a pure reactivation session, enhancers of memory expression should permanently improve retention and, therefore, facilitate retrieval both in that and in subsequent sessions. Using two well-known retrieval enhancers, noradrenaline and adrenocorticotropin(1-24), we could not find any evidence suggestive of reconsolidation. Hence, our results indicate that there is no retrieval-induced, protein synthesis-dependent process that would cause reconsolidation of IA memory.     

Classical conditioning of beginning reading responses

The present study describes the first demonstration that laboratory-controlled experimental procedures can lead to the successful acquisition and subsequent retention of classically conditioned beginning reading responses (CCBRRs) in children of both sexes and mean age of 4 yr. Anticipatory instructions combined with higher-order classical conditioning temporally arranged into a trace conditioning paradigm presented for 10 trials for each response to be learned led to beginning reading responses being successfully acquired by 20 children during 95% of the 2,220 total acquisition learning trials and subsequently correctly recalled on 114 of the 222 retention test trials. Findings support the view that perhaps the relatively sudden and sustained acquisition learning curves for reading responses on the second-signalling-system level of behavior in the present study may be quite different from the relatively slow and incremental learning curves usually obtained in classical conditioning of the autonomic type which occur on the first-signalling-system level.     

Is the medial amygdala part of the neural circuit modulating conditioned defeat in Syrian hamsters?

Conditioned defeat is a model wherein hamsters that have previously experienced a single social defeat subsequently exhibit heightened levels of avoidance and submission in response to a smaller, non-aggressive intruder. While we have previously demonstrated the critical involvement of the basolateral and central nuclei of the amygdala in the acquisition and expression of conditioned defeat, the role of the medial amygdala has yet to be investigated. In Experiment 1, muscimol, a GABA(A) receptor agonist, was infused bilaterally into the MeA prior to initial defeat training. Experiment 2 examined the effects of muscimol injections given prior to subsequent testing with a non-aggressive intruder. Finally, in Experiment 3, anisomycin was used to block protein synthesis in the medial and basolateral amygdala to examine the involvement of these nuclei in memory consolidation related to conditioned defeat. Submissive behavior was significantly reduced in animals that received muscimol prior to initial defeat training as well as in animals injected prior to testing with the non-aggressive intruder, indicating that the MeA is necessary for the acquisition and expression of conditioned defeat. In Experiment 3, however, anisomycin reduced conditioned defeat only when administered into the BLA, and not when injected into the MeA. The results of the present series of experiments suggest that, while the MeA may serve an important gateway for sensory information that is crucial for conditioned defeat, it does not appear to play a role in the plasticity including this behavioral response to social defeat.     

Intra-basolateral amygdala infusions of AP-5 impair or enhance retention of inhibitory avoidance depending on training conditions

Previous evidence has suggested that N-methyl-D-aspartate receptors (NMDARs) in the basolateral amygdala (BLA) are critically involved in the acquisition of aversively based learning tasks. However, the role of NMDARs in the BLA in the consolidation of memory of aversive training has not been well elucidated. In the present study, the NMDAR antagonist AP-5 (1 or 3 microg) was infused into the BLA of male Sprague-Dawley rats immediately before, immediately after, or 6h after training on an inhibitory avoidance task with either a high footshock (HFS; only high dose of AP-5 given) or a low footshock (LFS; both doses of AP-5 given). The 48 h retention of animals given AP-5 (3 microg) immediately before or after HFS training was significantly impaired compared to that of vehicle-controls. In contrast, the retention of rats given AP-5 (3 microg) immediately after LFS training was significantly enhanced compared to that of vehicle-controls. AP-5 (3 microg) infusions administered 6h after training with either an HFS or LFS did not affect retention. These findings suggest that the NMDARs in the BLA are involved in both the acquisition and consolidation of aversive memory. In addition, the AP-5-induced enhancement of memory obtained with LFS training suggests that NMDARs in the BLA are involved in other mechanisms influencing synaptic transmission, in addition to their well-established role in neuroplasticity.     

Memory enhancement induced by post-training intrabasolateral amygdala infusions of beta-adrenergic or muscarinic agonists requires activation of dopamine receptors: Involvement of right, but not left, basolateral amygdala

Previous findings indicate that the noradrenergic, dopaminergic, and cholinergic innervations of the basolateral amygdala (BLA) modulate memory consolidation. The current study investigated whether memory enhancement induced by post-training intra-BLA infusions of a beta-adrenergic or muscarinic cholinergic agonist requires concurrent activation of dopamine (DA) receptors in the BLA. Rats with implanted BLA cannulae were trained on an inhibitory avoidance (IA) task and, 48 h later, tested for retention. Infusions of the beta-adrenergic agonist clenbuterol into the right BLA, but not the left, enhanced retention, and concurrent infusions of the nonspecific DA receptor antagonist cis-Flupenthixol (Flu) blocked the enhancement. Post-training infusions of the muscarinic agonist oxotremorine into the right BLA also enhanced retention, and concurrent infusions of Flu blocked this effect. Additional experiments investigated whether memory modulation was lateralized to the right BLA. Post-training DA infusions into the right BLA, but not the left, enhanced retention. Post-training infusions of lidocaine or muscimol, which impair retention when infused bilaterally, had no effect when infused unilaterally into either the right or left BLA. These findings, together with earlier work, suggest that the dopaminergic system in the BLA is critically involved in memory modulation induced by noradrenergic and cholinergic influences. Additionally, these findings indicate that the enhancement, but not impairment, of memory consolidation is lateralized to the right BLA.     

Temporary basolateral amygdala lesions disrupt acquisition of socially transmitted food preferences in rats

Lesions of the basolateral amygdala (BLA) have long been associated with abnormalities of taste-related behaviors and with failure in a variety of taste- and odor-related learning paradigms, including taste-potentiated odor aversion, conditioned taste preference, and conditioned taste aversion. Still, the general role of the amygdala in chemosensory learning remains somewhat controversial. In particular, it has been suggested that the amygdala may not be involved in a form of chemosensory learning that has recently received a substantial amount of study-socially transmitted food preference (STFP). Here, we provide evidence for this involvement by pharmacologically inactivating the basolateral amygdala bilaterally during STFP training. The same inactivation sites that impaired taste aversion learning eliminated the normally conditioned preference for a food smelled on a conspecific's breath. Impairments of learned preference persisted even in testing sessions in which BLA was not inactivated, and learning was normal when the BLA was inactivated only during testing sessions; thus, the impairment was a true acquisition deficit. In conjunction with previous results from other paradigms, therefore, our data suggest that the amygdala is vital for learning procedures involving pairings of potent and arbitrary chemosensory stimuli.     

Antibody to amyloid beta protein alleviates impaired acquisition,retention, and memory processing in SAMP8 mice

SAMP8 (senescence-accelerated mouse, P8 strain) mice overproduce amyloid precursor protein and beta-amyloid and have learning and memory deficits. Preliminary data have indicated that overproduction of beta-amyloid plays a role in the pathogenesis of acquisition and retention deficits in SAMP8 mice. In the studies reported here, the authors examined the effects of polyclonal and monoclonal antibodies to beta-amyloid on acquisition and retention in an aversive T-maze testing paradigm when injected intracerebroventricularly (ICV) into 12-month SAMP8/TaJF mice. Both the polyclonal and monoclonal antibodies improved acquisition and retention when injected ICV 1 to 14 days prior to acquisition testing. Injection of all three antibodies intrahippocampally immediately following training improved retention on the T-maze when mice were tested 7 days later. The authors next studied the effect of monoclonal beta-amyloid antibody injected 48 h prior to training on the effect on retention in the T-maze of drugs modulating classical neurotransmitters. Arecoline and glutamate were injected directly into the hippocampus, and ketanserin, methiothepen, bicuculline, and OH-saclofen were injected into the septum. Previously, the authors have found that the doses of these drugs required to improve retention are markedly altered in 12-month SAMP8/TkJF mice compared to 4-month P8 mice. In these studies, it was demonstrated that antibody to beta-amyloid resulted in these drugs improving retention at doses that improved memory in 4-month SAMP8/TaJF mice. Based on these findings, we conclude that beta-amyloid overproduction is at least in part responsible for the acquisition and memory deficits in 12-month-old SAMP8/TaJF mice. Antibody to beta-amyloid restores the retention response to neurotransmitter manipulation to that seen in 4-month-old mice. beta-amyloid appears to play a key role in the loss of acquisition and retention seen in SAMP8/TaJF mice.     

对体液免疫反应的条件反射性调节

以饮糖精水作为条件刺激(conditioned stimulus,CS),腹腔注射免疫抑制剂环磷酰胺作为非条件刺激(unconditioned stimulus,UCS)训练Wistar大鼠,3天后腹腔注射卵清蛋白(ovalbunfin,OVA)抗原,观察再次单独条件刺激对原发性体液免疫反应的作用。结果发现．一次CU-UCS结合训练导致CS组大鼠对再现糖精水产生厌恶反应,外周血中抗OVA-IgG抗体水平显著低于UCS组。两次CS-UCS结合训练并多次给予条件刺激后,CS组大鼠抗OVA-IgG的条件性免疫抑制效应与一次CS-UCS结合训练及再次给予一次条件刺激的反应类同。这些结果证明条件刺激增强了环磷酰胺对动物原发性体液免疫反应的抑制作用．这种条件性体液免疫抑制作用是相对稳定和有限度的,不易受条件反射建立参数的影响。     

The role of the nucleus basalis magnocellularis in fear conditioning consolidation in the rat

The nucleus basalis magnocellularis (NBM) is known to be involved in the memorization of several conditioned responses. To investigate the role of the NBM in fear conditioning memorization, this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that had undergone fear training to acoustic conditioned stimulus (CS) and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as the conditioned freezing duration measured during retention testing, always performed 72 and 96 h after TTX administration. In this way, there was no interference with normal NBM function during either acquisition or retrieval phases, allowing any amnesic effect to be due only to consolidation disruption. The results show that for contextual fear response memory consolidation, NBM functional integrity is necessary up to 24 h post-acquisition. On the other hand, NBM functional integrity was shown to be necessary for memory consolidation of the acoustic CS fear response only immediately after acquisition and not 24-h post-acquisition. The present findings help to elucidate the role of the NBM in memory consolidation and better define the neural circuits involved in fear memories.     

High Level of Footshock during Inhibitory Avoidance Training Prevents Amnesia Induced by Intranigral Injection of GABA Antagonists

Disruption of synaptic activity of a number of cerebral structures (e.g., neostriatum, amygdala, and thalamus) produces marked deficits in retention of instrumentally conditioned behaviors. When animals are given a relatively high number of training trials or high intensities of footshock during learning, however, such disruption is considerably less effective. Since there is a close anatomical and functional relationship between the neostriatum and the substantia nigra, it was of interest to determine whether enhanced training with a high level of footshock would prevent the reported amnesic state induced by injections of GABA antagonists into the latter structure. Rats were trained in a one-trial inhibitory task, using 0.2 or 0.4 mA, and then injected with microgram quantities of picrotoxin or bicuculline into the substantia nigra and posterior region of the zona incerta; retention was measured 24 h later. Only those groups that had been injected into the nigra and trained with 0.2 mA showed amnesia. These results support the hypotheses that (a) the normal activity of a set of structures is essential for the development of memory consolidation and (b) after an enhanced learning experience these structures may participate in memory consolidation, but are not necessary for the occurrence of this process.     

Modulation of memory consolidation by the basolateral amygdala or nucleus accumbens shell requires concurrent dopamine receptor activation in both brain regions

Previous findings indicate that the basolateral amygdala (BLA) and the nucleus accumbens (NAc) interact in influencing memory consolidation. The current study investigated whether this interaction requires concurrent dopamine (DA) receptor activation in both brain regions. Unilateral, right-side cannulae were implanted into the BLA and the ipsilateral NAc shell or core in male Sprague-Dawley rats ( approximately 300 g). One week later, the rats were trained on an inhibitory avoidance (IA) task and, 48 h later, they were tested for retention. Drugs were infused into the BLA and NAc shell or core immediately after training. Post-training intra-BLA infusions of DA enhanced retention, as assessed by latencies to enter the shock compartment on the retention test. Infusions of the general DA receptor antagonist cis-Flupenthixol (Flu) into the NAc shell (but not the core) blocked the memory enhancement induced by the BLA infusions of DA. In the reverse experiment, post-training intra-NAc shell infusions of DA enhanced retention and Flu infusions into the BLA blocked the enhancement. These findings indicate that BLA modulation of memory consolidation requires concurrent DA receptor activation in the NAc shell but not the core. Similarly, NAc shell modulation of memory consolidation requires concurrent DA receptor activation in the BLA. Together with previous findings, these results suggest that the dopaminergic innervation of the BLA and NAc shell is critically involved in the modulation of memory consolidation.     

Lasting increases in basolateral amygdala activity after emotional arousal: implications for facilitated consolidation of emotional memories

Manipulations that reduce or enhance the activity of basolateral amygdala (BLA) neurons in the minutes to hours after training have been shown to respectively impair or facilitate retention on the inhibitory avoidance task. Although this suggests that BLA activity is altered after emotional arousal, such changes have not been directly demonstrated. To test this, we devised a feline analog of the inhibitory avoidance task and recorded BLA unit activity before and after a single inescapable footshock. Single-unit recordings revealed that the firing rate of many BLA neurons gradually increased after the footshock, peaking 30-50 min post-shock and then subsiding to baseline levels 2 h later. During this period of increased activity, the discharges of simultaneously recorded BLA cells were more synchronized than before the shock. Although it was known that pairing innocuous (conditioned stimulus, CS) and noxious stimuli modifies the responsiveness of BLA neurons to the CS, our results constitute the first demonstration that emotional arousal produces lasting increases in the spontaneous firing rates of BLA neurons. We propose that these changes in BLA activity may promote Hebbian interactions between coincident but spatially distributed activity patterns in BLA targets, facilitating the consolidation of emotional memories.